Next available on Tuesday 9 a.m.–5 p.m.

Additional Options

Search Results

504,859 results sorted by

  • Article

    Boosting expression level of plectasin in recombinant Pichia pastoris via 2A self-processing peptide assembly

    Authors
    Liang, Xingxing; Jiang, Hong; Si, Xiandong; Xin, Qi; Meng, Di; Chen, Peng; Mao, Xiangzhao
    Part of
    Applied microbiology and biotechnology, 2022-05, Vol.106 (9-10), p.3669-3678
    Abstract
    • Plectasin is a promising and potent antimicrobial peptide isolated from the fungus Pseudoplectania nigrella which has been heterologously expressed in various hosts. In this study, a four-copy cassette of plectasin was constructed via 2A peptide assembly to further increase its expression level in recombinant Pichia pastoris . The yeast transformant 4Ple-61 harboring four-copy cassette of plectasin could secrete 183.2 mg/L total protein containing 60.8% of plectasin at the flask level within 120 h, which was 2.3 times higher than that of the yeast transformant Ple-6 carrying one-copy cassette of plectasin. Western blot confirmed the significant peptide expression level in the transformant 4Ple-61. Furthermore, it yielded as high as 426.3 mg/L total protein within 120 h during a 5-L fermentation. The purified plectasin shows superior stability and good antimicrobial activity against conventional Staphylococcus aureus ATCC 26,001 and some food-borne antibiotic-resistant S. aureus strains with the MICs ranging from 8 to 32 μg/mL. Therefore, the strategy based on 2A peptide assembly can enhance the expression of plectasin and further expand its application prospect. Key points
      • A yeast transformant 4Ple-61 with four-copy cassette of plectasin was constructed.
      • The plectasin level yield by the transformant 4Ple-61 was boosted by 2.3 times.
      • The plectasin showed good activity against food-borne antibiotic-resistant S. aureus.
    Subjects
    Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial peptides; Assembly; Biomedical and Life Sciences; Biotechnologically Relevant Enzymes and Proteins; Biotechnology; Drug resistance; Fermentation; Food; Gene expression; Genetic aspects; Life Sciences; Microbial Genetics and Genomics; Microbiology; Peptides; Physiological aspects; Pichia pastoris; Proteins; Staphylococcus aureus; Yeast; Yeast fungi; Yeasts
  • Article

    First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies

    Authors
    Weiss, Glen J.; Chao, Joseph; Neidhart, Jeffrey D.; Ramanathan, Ramesh K.; Bassett, Dawn; Neidhart, James A.; Choi, Chung Hang J.; Chow, Warren; Chung, Vincent; Forman, Stephen J.; Garmey, Edward; Hwang, Jungyeon; Kalinoski, D. Lynn; Koczywas, Marianna; Longmate, Jeffrey; Melton, Roger J.; Morgan, Robert; Oliver, Jamie; Peterkin, Joanna J.; Ryan, John L.; Schluep, Thomas; Synold, Timothy W.; Twardowski, Przemyslaw; Davis, Mark E.; Yen, Yun
    Part of
    Investigational new drugs, 2013-08, Vol.31 (4), p.986-1000
    Abstract
    • Summary Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m 2 and later bi-weekly at 12, 15, and 18 mg/m 2 . The maximum tolerated dose (MTD) was determined at 15 mg/m 2 bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39–79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD ( n  = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT T max values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing.
    Subjects
    Adult; Aged; Antineoplastic agents; Area Under Curve; Biological and medical sciences; Biopsy; Camptothecin - adverse effects; Camptothecin - blood; Camptothecin - pharmacokinetics; Camptothecin - therapeutic use; Cancer therapies; Cellulose - adverse effects; Cellulose - blood; Cellulose - pharmacokinetics; Cellulose - therapeutic use; Chemotherapy; Clinical trials; Cyclodextrins - adverse effects; Cyclodextrins - blood; Cyclodextrins - pharmacokinetics; Cyclodextrins - therapeutic use; Demography; Disease-Free Survival; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Female; General aspects; Humans; Immunohistochemistry; Male; Maximum Tolerated Dose; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nanoparticles; Nanoparticles - adverse effects; Nanoparticles - therapeutic use; Neoplasm Staging; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - pathology; Oncology; Ovarian cancer; Patients; Permeability; Pharmaceutical sciences; Pharmacodynamics; Pharmacokinetics; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phase II Studies; Plasma; Polymers; Studies; Tomography, X-Ray Computed; Treatment Outcome; Tumors
  • Article

    Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma

    Authors
    Wick, Antje; Desjardins, Annick; Suarez, Cristina; Forsyth, Peter; Gueorguieva, Ivelina; Burkholder, Tiana; Cleverly, Ann Louise; Estrem, Shawn T.; Wang, Shuaicheng; Lahn, Michael M.; Guba, Susan C.; Capper, David; Rodon, Jordi
    Part of
    Investigational new drugs, 2020-10, Vol.38 (5), p.1570-1579
    Abstract
    • Summary Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study ( N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX ( n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.
    Subjects
    Anticancer properties; Antitumor activity; Disease control; Dosage; Glioblastoma; Glioma; Growth factors; Health services; Inhibitors; Life Sciences & Biomedicine; Lymphocytes T; Medicine; Medicine & Public Health; Oncology; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology; Pharmacology & Pharmacy; Pharmacology/Toxicology; Phase II Studies; Safety; Science & Technology; Survival; Temozolomide; Transforming growth factor-b
  • Article

    A novel bicistronic expression system composed of the intraflagellar transport protein gene ift25 and FMDV 2A sequence directs robust nuclear gene expression in Chlamydomonas reinhardtii

    Authors
    Dong, Bin; Hu, He-He; Li, Zhen-Fang; Cheng, Rong-Qiang; Meng, De-Mei; Wang, Junping; Fan, Zhen-Chuan
    Part of
    Applied Microbiology and Biotechnology, 2017-05, Vol.101 (10), p.4227-4245
    Abstract
    • Chlamydomonas reinhardtii offers a great promise for large-scale production of multiple recombinant proteins of pharmaceutical and industrial interest. However, the nuclear-encoding transgenes usually are expressed at a low level, which severely hampers the use of this alga in molecular farming. In this study, the promoter of the endogenous intraflagellar transport 25 (IFT25) gene of C. reinhardtii was tested for its ability to drive the expression of green fluorescent protein (GFP), which functions as a readout for target gene expression . IFT25 promoter (IFT25P) alone was not able to drive GFP expression to a detectable level. IFT25P, however, can drive robust IFT25-GFP fusion protein expression when the intron-containing IFT25 gene was inserted between IFT25P and GFP cDNA. When an extended version of foot-and-mouth virus 2A protease (2A E ) sequence was further inserted between the intron-containing IFT25 gene and the GFP cDNA, discrete GFP protein was observed to release from the IFT25-2A E -GFP polyprotein via 2A self-cleaving with a cleavage efficacy of approximately 99%. The monomer GFP was accumulated to a level of as high as 0.68% of total soluble proteins. To test whether the newly developed bicistronic IFT25P-IFT25-2A E expression system can be used to overexpress heterologous proteins of different origins and sizes, we inserted codon-optimized cDNAs encoding a Trichoderma reesei xylanase1 (25 kDa) and a Lachnospiraceae bacterium ND2006 type V CRISPR-Cas protein LbCpf1 (147 kDa) to the vector and found that the production of xylanase1 and LbCpf1 was as high as 0.69 and 0.49% of total soluble protein. Our result showed that IFT25P-IFT25-2A E system is more efficient to drive nuclear gene expression in C. reinhardtii than other conventionally used promoters, thus representing a novel efficient recombinant protein expression tool and has the potential to be scaled for commercial production of nuclear-encoded recombinant proteins of different sizes and origins in C. reinhardtii .
    Subjects
    Algae; Analysis; Antibiotics; Applied Genetics and Molecular Biotechnology; Applied Microbiology and Biotechnology; Biomedical and Life Sciences; Bioreactors; Biotechnology; Chlamydomonas reinhardtii; Chlamydomonas reinhardtii - genetics; Codon; Codons; DNA, Complementary; Fluorescence; Foot-and-mouth disease virus; Gene Expression; General Medicine; Genes; Genetic recombination; Genetic research; Genomes; Green Fluorescent Proteins - genetics; Heat shock proteins; Hypocrea jecorina; Life Sciences; Luminescent Proteins - genetics; Microbial Genetics and Genomics; Microbiology; Pharmaceutical sciences; Promoter Regions, Genetic; Protein expression; Recombinant Fusion Proteins - biosynthesis; Recombinant proteins; Studies; Transgenes; Viral Proteins - genetics
  • Article

    RAEP 2a edicao 2023

    Author
    Iizuka, Edson Sadao
    Part of
    Administração (São Paulo), 2023-05, Vol.24 (2), p.1
  • Article

    Chateau Margaux for Seat 2A

    Author
    Yeoman, Ian
    Part of
    Journal of revenue and pricing management, 2018-08, Vol.17 (4), p.201-203
    Subjects
    Business and Management; Editorial
  • Article

    Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study

    Authors
    Joerger, Markus; Hundsberger, Thomas; Haefliger, Simon; von Moos, Roger; Hottinger, Andreas F.; Kaindl, Thomas; Engelhardt, Marc; Marszewska, Michalina; Lane, Heidi; Roth, Patrick; Stathis, Anastasios
    Part of
    Investigational new drugs, 2023-04, Vol.41 (2), p.267-275
    Abstract
    • Purpose.  Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m 2 . Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study.  Methods.  This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle.  Results.  Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment.  Conclusion.  This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360.
    Subjects
    Anticancer properties; Antitumor activity; Antitumor agents; Brain cancer; Cancer; Female; Glioblastoma; Humans; Medicine; Medicine & Public Health; Neoplasm Recurrence, Local - drug therapy; Oncology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Patients; Pharmacology/Toxicology; Platinum; Safety; Stomach cancer; Tumors
  • Article

    Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study

    Authors
    Joerger, Markus; Hundsberger, Thomas; Haefliger, Simon; von Moos, Roger; Hottinger, Andreas F; Kaindl, Thomas; Engelhardt, Marc; Marszewska, Michalina; Lane, Heidi; Roth, Patrick; Stathis, Anastasios
    Abstract
    • Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m$^{2}$. Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study. Methods. This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle. Results. Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma.
    Subjects
    Avanbulin; BAL101553; Clinic for Neurology; Glioblastoma; Lisavanbulin; Medicine & health; Microtubule-targeting agent; Pharmacology (medical), Pharmacology, Oncology
  • Article

    Protein phosphatase 2A promotes the transition to G0 during terminal differentiation in Drosophila

    Authors
    Sun, Dan; Buttitta, Laura
    Part of
    Development (Cambridge), 2015-09, Vol.142 (17), p.3033-3045
    Abstract
    • Protein phosphatase type 2A complex (PP2A) has been known as a tumor suppressor for over two decades, but it remains unclear exactly how it suppresses tumor growth. Here, we provide data indicating a novel role for PP2A in promoting the transition to quiescence upon terminal differentiation in vivo. Using Drosophila eyes and wings as a model, we find that compromising PP2A activity during the final cell cycle prior to a developmentally controlled cell cycle exit leads to extra cell divisions and delays entry into quiescence. By systematically testing the regulatory subunits of Drosophila PP2A, we find that the B56 family member widerborst (wdb) is required for the role of PP2A in promoting the transition to quiescence. Cells in differentiating tissues with compromised PP2A retain high Cdk2 activity when they should be quiescent, and genetic epistasis tests demonstrate that ectopic Cyclin E/Cdk2 activity is responsible for the extra cell cycles caused by PP2A inhibition. The loss of wdb/PP2A function cooperates with aberrantly high Cyclin E protein levels, allowing cells to bypass a robust G0 late in development. This provides an example of how loss of PP2A can cooperate with oncogenic mutations in cancer. We propose that the PP2A complex plays a novel role in differentiating tissues to promote developmentally controlled quiescence through the regulation of Cyclin E/Cdk2 activity.
    Subjects
    Amino Acid Sequence; Anaphase-Promoting Complex-Cyclosome - metabolism; Animals; Cell Differentiation; Cyclin E - metabolism; Cyclin-Dependent Kinase 2 - chemistry; Cyclin-Dependent Kinase 2 - metabolism; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; E2F Transcription Factors - metabolism; Epistasis, Genetic; Molecular Sequence Data; Organogenesis; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Protein Binding; Protein Structure, Secondary; Protein Subunits - metabolism; Resting Phase, Cell Cycle
  • Article

    Editorial – RAEP 2ª edição 2023

    Author
    Iizuka, Edson Sadao
    Part of
    Administração (São Paulo), 2023-05, Vol.24 (2), p.1-4
    Abstract
    • Em seguida, apresentamos o artigo intitulado "Profissionalidade e os Fatores Didáticos Contribuintes ao Desempenho Docente" que foi um trabalho desenvolvido por Alexandre Borba Salvador, pesquisador da ESPM; João Paulo Resende de Lima pesquisador da Universidade de São Paulo (USP); e, Vitor Koki da Costa Nogami, pesquisador da Universidade Estadual de Maringá (UEM), e teve como objetivo central identificar os fatores didáticos contribuintes ao desempenho docente em cursos de pós-graduação lato sensu. O quarto artigo "Use Of Social Representation To Validate The Structural Equations Modelling in Management" escrito por Gustavo Guimarães Marchisotti; José Rodrigues de Farias Filhos e Sérgio Luiz Braga França, pesquisadores da Universidade Federal Fluminense (UFF); Hélio Cristiano Gomes Alves de Castro, pesquisador do Instituto Superior de Educação Personalizada - ISEP; e Fátima Bayma de Oliveira, pesquisadora da Fundação Getulio vargas - FGV/EBAPE, apresenta a utilização da teoria das representações sociais para validar o modelo estrutural de modelagem de equações estruturais e melhor compreender o objeto de pesquisa em Administração. O caso contribui ao fomentar reflexões sobre tópicos atuais e relevantes ao setor de alimentação fora do lar, aplicáveis a outros setores e tipos organizacionais. O último trabalho caracterizado por um relato de prática, intitulado "Educação 4.0 e Docência em Cursos de Gestão: O que Podemos Aprender com o Designer Educacional?", apresenta uma experiência sobre o curso Design Educacional Descomplicado, ofertado com o objetivo de auxiliar docentes dos cursos de gestão, na criação, desenvolvimento e avaliação de disciplinas presenciais. Os fatos apresentados neste relato trazem importantes implicações para aqueles envolvidos no processo de aprimoramento continuado dos docentes, evidenciando que ao incorporar os conhecimentos sobre design educacional, com destaque para o modelo ADDIE, o processo contribuiu para aumentar a confiança na adoção de TDICs, com efeitos positivos sobre a prática docente.
    Subjects
    Design
  • Article

    Antimicrobial compounds produced by Lactobacillus sakei subsp. sakei 2a, a bacteriocinogenic strain isolated from a Brazilian meat product

    Authors
    de Carvalho, Kátia G; Bambirra, Felipe H. S; Kruger, Monika F; Barbosa, Matheus S; Oliveira, Jamil S; Santos, Alexandre M. C; Nicoli, Jacques R; Bemquerer, Marcelo P; de Miranda, Antonio; Salvucci, Emiliano J; Sesma, Fernando J. M; Franco, Bernadette D. G. M
    Part of
    Journal of industrial microbiology & biotechnology, 2010-04, Vol.37 (4), p.381-390
    Abstract
    • Bacteriocins produced by lactic acid bacteria are gaining increased importance due to their activity against undesirable microorganisms in foods. In this study, a concentrated acid extract of a culture of Lactobacillus sakei subsp. sakei 2a, a bacteriocinogenic strain isolated from a Brazilian pork product, was purified by cation exchange and reversed-phase chromatographic methods. The amino acid sequences of the active antimicrobial compounds determined by Edman degradation were compared to known protein sequences using the BLAST-P software. Three different antimicrobial compounds were obtained, P1, P2 and P3, and mass spectrometry indicated molecular masses of 4.4, 6.8 and 9.5 kDa, respectively. P1 corresponds to classical sakacin P, P2 is identical to the 30S ribosomal protein S21 of L. sakei subsp. sakei 23 K, and P3 is identical to a histone-like DNA-binding protein HV produced by L. sakei subsp. sakei 23 K. Total genomic DNA was extracted and used as target DNA for PCR amplification of the genes sak, lis and his involved in the synthesis of P1, P2 and P3. The fragments were cloned in pET28b expression vector and the resulting plasmids transformed in E. coli KRX competent cells. The transformants were active against Listeria monocytogenes, indicating that the activity of the classical sakacin P produced by L. sakei 2a can be complemented by other antimicrobial proteins.
    Subjects
    Anti-Infective Agents - chemistry; Anti-Infective Agents - isolation & purification; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Antimicrobial agents; Bacteria; Bacteria - drug effects; Bacteriocins - biosynthesis; Bacteriocins - chemistry; Bacteriocins - isolation & purification; Bacteriocins - pharmacology; Biochemistry; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biotechnology; Brazil; Chromatography; Chromatography, Liquid - methods; Cloning, Molecular; DNA, Bacterial - genetics; DNA, Bacterial - isolation & purification; E coli; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression; Genetic Engineering; Inorganic Chemistry; Lactobacillus - isolation & purification; Lactobacillus - metabolism; Life Sciences; Listeria; Mass Spectrometry; Meat products; Meat Products - microbiology; Microbial Sensitivity Tests; Microbiology; Molecular Weight; Original Paper; Peptides; Plasmids; Polymerase Chain Reaction; Proteins; Salmonella; Sequence Analysis, Protein; Studies
  • Newsletterarticle

    Providing Cc Roads At Ep.no.2a/4 To Ep.no. 2a/7 At Landagarurvu In Ward No.98

    Part of
    MENA Report, 2022
  • Article

    Persistence of legacy soil P and elevated background water P concentrations in Water Conservation Area 2A, a northern Everglades wetland

    Authors
    Juston, John M.; Kadlec, Robert H.; DeBusk, William F.; Jerauld, Mike J.; DeBusk, Thomas A.
    Part of
    Water resources research, 2015-12, Vol.51 (12), p.9746-9762
    Abstract
    • Upstream source control and Stormwater Treatment Areas (STAs) have reduced phosphorus (P) loads to Water Conservation Area 2A (WCA‐2A), a northern Everglades wetland, by three quarters since year 2000. Nevertheless, large storages of P remain in enriched peat soils and it is unclear how legacy stores will impact spatial and temporal scales of recovery. We remeasured soil P enrichment along a well‐studied eutrophication gradient in WCA‐2A and applied a profile modeling approach with uncertainty analysis to assess changes in longitudinal soil P gradients 13 years after load reductions. We then analyzed existing internal water P data, using a novel data screening approach, for evidence of lowest possible water P concentrations independent from inflows. We interpret such water P limits as evidence of the strength of internal loading at a location. Results indicate that soil P enrichment persists in the ∼7.5 km long “impacted” zone, with no significant evidence of net advancement or recession, while a large pool of labile P in the flocculent layer consolidated and diminished. There is indeed evidence, both spatial and temporal, that this extensive zone of enriched soil P continues to elevate lowest achievable water P concentrations. The corresponding gradient of elevated water P limits is both receding and diminishing since load reductions, thus providing further evidence toward recovery. However, results also suggest that these “transitory P limits” due to internal loading are likely to persist for decades above water quality targets. These results advance our understanding of recovery in impacted wetlands and are relevant to Everglades restoration. Key Points: P‐enriched soils elevate lowest possible water P levels above criteria via internal loading Wetland soil consolidated but P storage persisted 13 years after 75% external load reduction Recovery of wetland water quality can take decades due to persistence of legacy P stored in soils
    Subjects
    legacy nutrients; Load; phosphorus; recovery; remediation; Water conservation; Water quality; Wetlands
  • Article

    Inhibition equivalency factors for microcystin variants in recombinant and wild-type protein phosphatase 1 and 2A assays

    Authors
    Garibo, Diana; Flores, Cintia; Cetó, Xavier; Prieto-Simón, Beatriz; del Valle, Manel; Caixach, Josep; Diogène, Jorge; Camp s, Mònica
    Part of
    Environmental science and pollution research international, 2014-09, Vol.21 (18), p.10652-10660
    Abstract
    • In this work, protein phosphatase inhibition assays (PPIAs) have been used to evaluate the performance of recombinant PP1 and recombinant and wild-type PP2As. The enzymes have been compared using microcystins-LR (MC-LR) as a model cyanotoxin. Whereas PP2ARₑc provides a limit of detection (LOD) of 3.1 μg/L, PP1Rₑc and PP2AWᵢₗd provide LODs of 0.6 and 0.5 μg/L, respectively, lower than the guideline value proposed by the World Health Organization (1 μg/L). The inhibitory potencies of seven MC variants (-LR, -RR, -dmLR, -YR, -LY, -LW and -LF) have been evaluated, resulting on 50 % inhibition coefficient (IC₅₀) values ranging from 1.4 to 359.3 μg/L depending on the MC variant and the PP. The PPIAs have been applied to the determination of MC equivalent contents in a natural cyanobacterial bloom and an artificially contaminated sample, with multi-MC profiles. The inhibition equivalency factors (IEFs) have been applied to the individual MC quantifications determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and the estimated MC-LR equivalent content has been compared to PPIA results. PPIAs have demonstrated to be applicable as MC screening tools for environmental applications and to protect human and animal health.
    Subjects
    Aquatic Pollution; Atmospheric Protection/Air Quality Control/Air Pollution; Chromatography; Chromatography, Liquid; Cyanobacteria - chemistry; detection limit; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Enzyme Inhibitors - chemistry; Enzymes; Humans; inhibitory concentration 50; Kinases; Mass Spectrometry; microcystin-LR; Microcystins - chemistry; Performance evaluation; Phosphatase; phosphoprotein phosphatase; Protein Phosphatase 1 - antagonists & inhibitors; Protein Phosphatase 1 - chemistry; Protein Phosphatase 1 - genetics; Protein Phosphatase 1 - metabolism; Protein Phosphatase 2 - antagonists & inhibitors; Protein Phosphatase 2 - chemistry; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Proteins; Research Article; Scientific imaging; screening; Toxicity; Toxins; Waste Water Technology; Water Management; Water Pollution Control; World Health Organization
  • Article

    Double Candida antarctica lipase B co-display on Pichia pastoris cell surface based on a self-processing foot-and-mouth disease virus 2A peptide

    Authors
    Sun, Yu-Fei; Lin, Ying; Zhang, Jun-Hui; Zheng, Sui-Ping; Ye, Yan-Rui; Liang, Xing-Xiang; Han, Shuang-Yan
    Part of
    Applied microbiology and biotechnology, 2012-12, Vol.96 (6), p.1539-1550
    Abstract
    • To develop a high efficiency Candida antarctica lipase B (CALB) yeast display system, we linked two CALB genes fused with Sacchromyces cerevisiae cell wall protein genes, the Sed1 and the 3′-terminal half of Sag1 , separately by a 2A peptide of foot-and-mouth disease virus (FMDV) in a single open reading frame. The CALB copy number of recombinant strain KCSe2ACSa that harbored the ORF was identified, and the quantity of CALB displayed on the cell surface and the enzyme activity of the strain were measured. The results showed that the fusion of multiple genes linked by 2A peptide was translated into two independent proteins displayed on the cell surface of stain KCSe2ACSa. Judging from the data of immunolabeling assay, stain KCSe2ACSa displayed 94 % CALB-Sed1p compared with stain KCSe1 that harbored a single copy CALB-Sed1 and 64 % CALB-Sag1p compared with stain KCSa that harbored a single copy CALB-Sag1 on its surface. Besides, strain KCSe2ACSa possessed 170 % hydrolytic activity and 155 % synthetic activity compared with strain KCSe1 as well as 144 % hydrolytic activity and 121 % synthetic activity compared with strain KCSa. Strain KCSe2ACSa even owned 124 % hydrolytic activity compared with strain KCSe2 that harbored two copies CALB - Sed1 . The heterogeneous glycosylphosphatidylinositol-anchored proteins co-displaying yeast system mediated by FMDV 2A peptide was shown to be an effective method for improving the efficiency of enzyme-displaying yeast biocatalysts.
    Subjects
    Analysis; Applied Genetics and Molecular Biotechnology; Biomedical and Life Sciences; Biotechnology; Candida - enzymology; Candida - genetics; Candida antarctica; Foot & mouth disease; Foot-and-mouth disease; Foot-and-mouth disease virus; Foot-and-Mouth Disease Virus - genetics; Foot-and-Mouth Disease Virus - metabolism; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression; Life Sciences; Lipase; Lipase - genetics; Lipase - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Microbial Genetics and Genomics; Microbiology; Peptides; Peptides - genetics; Peptides - metabolism; Pichia - genetics; Pichia - metabolism; Pichia pastoris; Protein Engineering - methods; Protein Processing, Post-Translational; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Yeast
  • Newsletterarticle

    Providing Cc Roads At Ep.no.2a/4 To Ep.no. 2a/7 At Landagarurvu In Ward No.98 (3rd Call)

    Part of
    MENA Report, 2023
  • Article

    Combination of the 2A/furin technology with an animal component free cell line development platform process

    Authors
    Jostock, Thomas; Dragic, Zorica; Fang, Jianmin; Jooss, Karin; Wilms, Burkhard; Knopf, Hans-Peter
    Part of
    Applied microbiology and biotechnology, 2010-07, Vol.87 (4), p.1517-1524
    Abstract
    • The recently described 2A/furin technology combines both chains of the antibody in a single open reading frame. Upon translation and secretion, the peptide is processed by the cell to generate native fully functional IgG antibodies. Here, we describe the results of an evaluation study of this technology for an industrial CHO cell line development process. The 2A/furin expression cassette setup was combined with a Novartis vector system. A transfection, selection, and cloning procedure in chemically defined media was established at Novartis and applied for a monoclonal test antibody. The productivity of 2A/furin-vector-derived clones in non-optimized generic shake flask fed-batch models was in a comparable range with clones derived from the reference control vector. Higher clonal production stability was seen for the majority of clones generated with the 2A/furin technology compared to the clones generated with the reference control vector. Product quality was analyzed by SDS-PAGE and no significant difference was detected between the two systems. Thus, it was shown that the 2A/furin technology can be successfully combined with a Novartis CHO expression system and platform. Due to the single ORF setup, the 2A/furin technology may therefore offer a suitable approach to reduce vector size and complexity.
    Subjects
    2A/furin; Animals; Antibodies; Biological and medical sciences; Biomedical and Life Sciences; Biotechnology; Biotechnology - methods; Cell culture; CHO; CHO Cells; Cloning; Cricetinae; Cricetulus; Fundamental and applied biological sciences. Psychology; Furin - genetics; Furin - metabolism; Gene amplification; Gene Expression; Genetic Vectors - genetics; Genetic Vectors - metabolism; Genomes; Life Sciences; Light; Methods and Protocols; Microbial Genetics and Genomics; Microbiology; Plasmids; Productivity; Recombinant antibody production; Studies
  • Article

    Mining Residues Characterization and Sentinel-2A Mapping for the Valorization and Efficient Resource Use by Multidisciplinary Strategy

    Authors
    Guglietta, Daniela; Conte, Aida Maria; Paciucci, Matteo; Passeri, Daniele; Trapasso, Francesca; Salvatori, Rosamaria
    Part of
    Minerals (Basel), 2022-05, Vol.12 (5), p.617
    Abstract
    • Raw materials are essential for all sectors of the economy as well as for all innovative technologies. Currently, industry is largely dependent on imports and consumption of these materials, and in the future, following the global energy transition, this trend will drastically increase. For this reason, it is necessary to develop new strategies to meet the supply–demand of raw materials by strategic sectors and technologies. To this end, mining residues are turning into viable raw materials sources as they represent reliable access to valuable resource supply. This work aims to validate a methodology providing more in-depth quali-quantitative information about 100 samples of mining residues collected in the Joda West mine (India) by multidisciplinary strategy in order to valorize and promote efficient resource use. In this paper, physicochemical and mineralogical characterization and hyperspectral signatures have been integrated with satellite Sentinel-2A data. In particular, the X-ray powder diffraction (XRPD), X-ray fluorescence (XRF), and scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) analyses indicated the presence of mining residues samples rich in raw materials that were possible to spectrally distinguish in order to use them as input for the object-oriented classification of a satellite image. The satellite resulting map highlighted four different classes of mining residues with mean concentrations of around 36% for hematite, 23.5% for quartz, 9% for kaolinite and 5% for pyrolusite. These results represent the possibility of transforming an environmental problem (mining residues) into a resource potentially exploitable by industries knowing their composition and position in the study area. Moreover, by doing so, it will be possible to ensure sustainable consumption of the raw materials and to build resilient economies and societies, minimizing environmental degradation.
    Subjects
    Analytical methods; Calibration; circular economy; Consumption; Electron microscopy; Environmental degradation; Environmental impact; Fluorescence; Haematite; Hematite; Image classification; Imports; Industry; Kaolinite; Materials; Mineralogy; Mining; Particle size; Pyrolusite; Raw materials; raw materials supply; Remote sensing; remote sensing classification; Residues; Samples; Satellite imagery; Scanning electron microscopy; Spaceborne remote sensing; Spectroscopy; Strategy; Sustainable use; X ray fluorescence; X ray powder diffraction; X rays
  • Article

    A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer

    Authors
    Kyriakopoulos, Christos E.; Heath, Elisabeth I.; Eickhoff, Jens C.; Kolesar, Jill; Yayehyirad, Mulusew; Moll, Thomas; Wilding, George; Liu, Glenn
    Part of
    Investigational new drugs, 2016-04, Vol.34 (2), p.225-230
    Abstract
    • Summary Background A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC). Methods This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days. Results Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1–3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1–8). Conclusions APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted.
    Subjects
    Aged; Aged, 80 and over; Androgens; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antioxidants; Antioxidants - pharmacokinetics; Antioxidants - therapeutic use; Cancer therapies; Chromans - pharmacokinetics; Chromans - therapeutic use; Clinical trials; Creatinine; Dose-Response Relationship, Drug; Drug dosages; Humans; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Nausea; Neoplasm Staging; Oncology; Oxidative stress; Patients; Pharmaceuticals; Pharmacology/Toxicology; Phase I Studies; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Signal transduction; Studies; Vitamin E; Vitamin E - therapeutic use
  • Newsletterarticle

    Road Re-paving Works And Related Works In Road Reserve At Jalan Semarak 2a, 2a/1, 2a/2, 2a/3, 3a And Side Lanes And Seroja Circle Section Bb7, Bandar Bukit Town For Hulu Selangor Municipal Council

    Part of
    MENA Report, 2024
  • Article

    Persistence of legacy soil P and elevated background water P concentrations in W ater C onservation A rea 2A, a northern E verglades wetland

    Authors
    Juston, John M.; Kadlec, Robert H.; DeBusk, William F.; Jerauld, Mike J.; DeBusk, Thomas A.
    Part of
    Water resources research, 2015-12, Vol.51 (12), p.9746-9762
    Abstract
    • Abstract Upstream source control and Stormwater Treatment Areas (STAs) have reduced phosphorus (P) loads to Water Conservation Area 2A (WCA‐2A), a northern Everglades wetland, by three quarters since year 2000. Nevertheless, large storages of P remain in enriched peat soils and it is unclear how legacy stores will impact spatial and temporal scales of recovery. We remeasured soil P enrichment along a well‐studied eutrophication gradient in WCA‐2A and applied a profile modeling approach with uncertainty analysis to assess changes in longitudinal soil P gradients 13 years after load reductions. We then analyzed existing internal water P data, using a novel data screening approach, for evidence of lowest possible water P concentrations independent from inflows. We interpret such water P limits as evidence of the strength of internal loading at a location. Results indicate that soil P enrichment persists in the ∼7.5 km long “impacted” zone, with no significant evidence of net advancement or recession, while a large pool of labile P in the flocculent layer consolidated and diminished. There is indeed evidence, both spatial and temporal, that this extensive zone of enriched soil P continues to elevate lowest achievable water P concentrations. The corresponding gradient of elevated water P limits is both receding and diminishing since load reductions, thus providing further evidence toward recovery. However, results also suggest that these “transitory P limits” due to internal loading are likely to persist for decades above water quality targets. These results advance our understanding of recovery in impacted wetlands and are relevant to Everglades restoration. Key Points: P‐enriched soils elevate lowest possible water P levels above criteria via internal loading Wetland soil consolidated but P storage persisted 13 years after 75% external load reduction Recovery of wetland water quality can take decades due to persistence of legacy P stored in soils
  • Article

    Multicenter validation of a multiplex PCR assay for differentiating the major Listeria monocytogenes serovars 1/2a, 1/2b, 1/2c, and 4b: toward an international standard

    Authors
    Doumith, M; Jacquet, C; Gerner-Smidt, P; Graves, L.M; Loncarevic, S; Mathisen, T; Morvan, A; Salcedo, C; Torpdahl, M; Vazquez, J.A
    Part of
    Journal of food protection, 2005-12, Vol.68 (12), p.2648-2650
    Abstract
    • The performance of a multiplex PCR assay that separates the four major serovars of the pathogenic Listeria monocytogenes into four distinct PCR groups was evaluated through a multicenter typing study. Identical panels of 90 Listeria isolates were distributed to five participating laboratories that were blind to the nature of the isolates. Isolates were characterized using the previously standardized protocol. Overall concordance was 96.6 to 100%, sufficient for the assay to be used as an alternative to serotyping and confidently applied in laboratories involved in L. monocytogenes typing.
    Subjects
    Animals; assays; bacterial contamination; Biological and medical sciences; Consumer Product Safety; food contamination; Food industries; Food Microbiology; food pathogens; Fundamental and applied biological sciences. Psychology; General aspects; genes; Humans; international cooperation; Listeria monocytogenes; Listeria monocytogenes - classification; Listeria monocytogenes - isolation & purification; Listeriosis - diagnosis; Listeriosis - microbiology; Methods of analysis, processing and quality control, regulation, standards; model validation; polymerase chain reaction; Polymerase Chain Reaction - methods; Polymerase Chain Reaction - standards; Reproducibility of Results; ribotypes; sanitation standard operating procedures; Sensitivity and Specificity; Serotyping; Species Specificity; virulence
  • Newsletterarticle

    Providing S.w Drain Fro Vcc (1m Vent) From E.p.no.25a/7/2a/2 To 25/a/7/2a/2 At Mutyamamba Colony (hill Lock Area) In Ward.no.94 (ggmp)

    Part of
    MENA Report, 2024
  • Article

    Crystal structure of the eukaryotic translation initiation factor 2A from Schizosaccharomyces pombe

    Authors
    Kashiwagi, Kazuhiro; Ito, Takuhiro; Yokoyama, Shigeyuki
    Part of
    Journal of Structural and Functional Genomics, 2014-09, Vol.15 (3), p.125-130
    Abstract
    • The eukaryotic translation initiation factor 2A (eIF2A) was identified as a factor that stimulates the binding of methionylated initiator tRNA (Met-tRNA i Met ) to the 40S ribosomal subunit, but its physiological role remains poorly defined. Recently, eIF2A was shown to be involved in unconventional translation initiation from CUG codons and in viral protein synthesis under stress conditions where eIF2 is inactivated. We determined the crystal structure of the WD-repeat domain of Schizosaccharomyces pombe eIF2A at 2.5 Å resolution. The structure adopts a novel nine-bladed β-propeller fold. In contrast to the usual β-propeller proteins, the central channel of the molecule has the narrower opening on the bottom of the protein and the wider opening on the top. Highly conserved residues are concentrated in the positively-charged top face, suggesting the importance of this face for interactions with nucleic acids or other initiation factors.
    Subjects
    Amino acids; Antigen presentation; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Crystal structure; Crystallography, X-Ray; Data collection; Datasets; E coli; Eukaryotic Initiation Factor-2 - genetics; Eukaryotic Initiation Factor-2 - ultrastructure; Forestry Management; General Medicine; Genetics; Glycerol; Hepatitis C; Human Genetics; Kinases; Life Sciences; Microbial Genetics and Genomics; Models, Molecular; Peptide Chain Initiation, Translational; Plant Genetics and Genomics; Protein Structure, Tertiary; Proteins; Ribosome Subunits, Small, Eukaryotic - genetics; RNA, Transfer, Met - genetics; Schizosaccharomyces - genetics; Schizosaccharomyces pombe; Structural Biology; Yeast
  • Article

    VULNERABILIDADES SOCIOECONÔMICAS DO ESTADO DO AMAZONAS AGRAVADAS PELA 2ª ONDA DA PANDEMIA DE COVID-19

    Authors
    Silva, Michele Lins Aracaty e; Mauricio Barbosa Lucas, Mauro; Marcelo dos Reis Braule Pinto, Leonardo
    Part of
    Informe GEPEC, 2022-02, Vol.26 (1), p.127-145
    Abstract
    • O Estado do Amazonas apresenta os mais elevados indicadores de vulnerabilidade socioeconômica, incluindo a pobreza, fome, vulnerabilidade, desigualdade social, baixa taxa de prosperidade social, renda per capita insuficiente, insegurança alimentar, informalidade e dependência de programas de transferência de renda, situação agravada com a chegada do COVID-19 visto a fragilidade do sistema de saúde. Tal realidade, pode explicar a necessidade da população mais vulnerável em romper as barreiras do isolamento social e permanecer nas ruas elevando a taxa de contaminação. Assim, este artigo tem como objetivo analisar as vulnerabilidades socioeconômicas do Estado do Amazonas de forma a justificar a baixa adesão ao isolamento social e de permanência em casa. Para tanto, baseia-se em pesquisa bibliográfica e documental com o uso de dados secundários do IBGE, ONU e IPEA, analisando os indicadores do IVS, IDHM, pobreza, extrema pobreza, fome, renda per capita, Índice de Gini e Taxa de Prosperidade Social. Os resultados mostraram avanço no IVS e no IDHM ao longo dos anos, elevado percentual de Pobreza, Pobreza Extrema e Desigualdade Social, elevado percentual de Insegurança Alimentar, Renda Per Capita e Taxa de Prosperidade Social baixas, elevado percentual de informalidade (58,35%) e de dependência de programa de transferência de renda (25%). Os números da saúde agravados pelo COVID-19, apontam a insuficiência de leitos, respiradores e de profissionais de saúde, elevada taxa de reprodução da doença, elevado grau de mortalidade e de coeficiente de incidência, baixo índice de isolamento social, elevado número de mortes diárias, colapso no sistema funerário e em relação à 2ª onda a crise por escassez de oxigênio de uso medicinal.
    Subjects
    Vulnerabilidade. Socioeconômicas. Desenvolvimento Regional. Amazonas. COVID-19
  • Article

    Ban Chiang's Contribution to Prehistory - Ban Chiang, Northeast Thailand, Volume 2A: Background to the Study of the Metal Remains. Edited by Joyce C. White and Elizabeth G. Hamilton. Philadelphia: University of Pennsylvania Press, 2018. 296 pp. ISBN: 9781931707213 (cloth). - Ban Chiang, Northeast Thailand, Volume 2B: Metals and Related Evidence from Ban Chiang, Ban Tong, Ban Phak Top, and Don Klang. Edited by Joyce C. White and Elizabeth G. Hamilton. Philadelphia: University of Pennsylvania Pres

    Author
    Van Esterik, Penny
    Part of
    The Journal of Asian Studies, 2020-08, Vol.79 (3), p.806-811
    Abstract
    • Chapter 3 debunks the conventional technological determinism paradigm about metals and prehistoric society and critiques past assumptions about adoption, independent development, evolutionary stages and ages, and the constant search for origins, arguing that they promote oversimplification and distort complex social processes. [...]prestige goods refer to goods produced for elite patrons or goods acquired by long-distance exchange to promote elite status in a stratified society, while valuables are not made for or controlled by elites but rather serve to integrate social groups through distribution at rites of passage or ritual gift exchanges. Attention is focused on copper, tin bronze, high-tin bronze, and low-carbon iron, metals that are used in the Ban Chiang artifacts analyzed in detail in the next monograph. Laboratory examination included metallography and elemental analyses, and was done on 163 copper-base and 8 iron artifacts, revealing that bronze technology arrived in the region well developed.
    Subjects
    Bans; Colleges & universities; Determinism; Elites; Iron; Metallurgy; Metals; Patrons; Prehistoric era; Prestige; Rites of passage; Social processes; Technology; Tin
  • Article

    A phase I/II trial of capecitabine combined with peginterferon [alpha]-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma

    Authors
    Ogasawara, Sadahisa; Chiba, Tetsuhiro; Ooka, Yoshihiko; Kanogawa, Naoya; Motoyama, Tenyu; Suzuki, Eiichiro; Tawada, Akinobu; Kanai, Fumihiko; Yokosuka, And Osamu
    Part of
    Investigational new drugs, 2014-08, Vol.32 (4), p.762
    Abstract
    • Background Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon [alpha]-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II). Methods Capecitabine was administered daily on days 1-14, while peginterferon [alpha]-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m^sup 2^--day)] and peginterferon [alpha]-2a ([mu]g/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively. Results A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events. Conclusion Capecitabine at 2000 mg/(m^sup 2^--day) combined with peginterferon [alpha]-2a (90 [mu]g/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.[PUBLICATION ABSTRACT]
    Subjects
    Cancer therapies; Clinical trials; Disease; Drug dosages; Drug therapy; Growth factors; Hematology; Hemoglobin; Liver cancer; Neutrophils; Patients; Statistical analysis
  • Newsletterarticle

    Lot 2a

    Part of
    MENA Report, 2023
  • Article

    2A top ten predictions

    Part of
    Arkansas business, 2012-07, Vol.29 (29), p.S92
    Subjects
    Evaluation; Football teams; Sports; United States
  • Article

    Influence of nonylphenol and octylphenol exposure on 5-HT, 5-HT transporter, and 5-HT 2A receptor

    Authors
    Liu, Chunhong; Lai, Yuting; Ouyang, Junyan; Yang, Tongwang; Guo, Youting; Yang, Jie; Huang, Shaowen
    Part of
    Environmental science and pollution research international, 2017-03, Vol.24 (9), p.8279
    Abstract
    • Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P < 0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P < 0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P < 0.05). Meanwhile, the expression levels of 5-HT in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P < 0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.
    Subjects
    Animals; Blood Platelets - drug effects; Blood Platelets - metabolism; Drug Interactions; Endocrine Disruptors; Male; Membrane Transport Proteins; Phenols - toxicity; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A - metabolism; Serotonin - blood; Serotonin Plasma Membrane Transport Proteins - metabolism; Toxicity Tests

Can't find what you're looking for?

Keyboard Shortcuts

Close

Available anywhere

?
Shortcut help message
s
Highlight search box
esc
Close dialog

Available in search results

n
Next page
p
Previous page
f
Toggle filters
1-5
Open nth result on page