41 research outputs found
Inhibition of human placenta glutathione transferase P1-1 by the antibiotic calvatic acid and its diazocyanide analogue--evidence for multiple catalytic intermediates
No full textThe inhibition mechanism of the dimeric human placenta glutathione transferase (GST) P1-1 by calvatic acid and the reaction intermediates, i.e. the diazocyanide analogue of calvatic acid, has been investigated at pH 7.0 and 30.0 degrees C. Experiments performed at different molar ratios of inhibitor/GST P1-1 indicate that 1 mol calvatic acid inactivates 1 mol GST P1-1, containing two catalytically equivalent active sites. However, 2 mol of the diazocyanide analogue of calvatic acid inactivate 1 mol GST P1-1. Two disulfide bridges/dimer, probably between Cys47 and Cys101, have been formed during the reaction of GST P1-1 with calvatic acid and its diazocyanide analogue. The apparent second-order rate constants for GST P1-1 inactivation by calvatic acid and its diazocyanide analogue are 2.4+/-0.3 M(-1) s(-1) and (8.5+/-0.7) x 10(3) M(-1) s(-1), respectively. The reaction of calvatic acid with free L-cysteine can be described by a simple process with an apparent second-order rate constant of (5.0+/-0.4) x 10(1) M(-1) s(-1). In contrast, a transient species occurs during the reaction of the diazocyanide analogue of calvatic acid with free L-cysteine. Kinetics may be described by a second-order process [the rate constant being (8.0+/-0.5) x 10(3) M(-1) s(-1)] followed by a first-order decay [the rate constant corresponding to (1.2+/-0.1) x 10(1) s(-1)]. Calvatic acid represents an enzyme inhibitor acting much slower than its reaction intermediates (i.e. its diazocyanide analogue)
BECKETT RESONATING IN ITALY: WHICH TEXT, WHOSE VOICE?
No full textThis paper deals with the issue of translating a self-translated text, focusing on the Italian version of Waiting for Godot by Carlo Fruttero published by Einaudi. In the 1950s, the status of self-translator was still unclear both for the author, who was developing the habit after the success of his first play, and for Fruttero. This produced a situation somewhat confusing: Fruttero translated originally the French play, but several modifications were later introduced starting from the English version in new issues in collected volumes. This was never disclosed in the paratext. The result is that two different Einaudi versions of the Italian Godot are available in the market today, one strictly from the very first French edition by Minuit, the other occasionally integrating or modifying from the English version by Beckett, which had in the meantime come out
Location Decisions and Nongovernmental Organization Motivation: Evidence from Rural Bangladesh
No full textNongovernmental organizations (NGOs)
play an increasingly important role in development
assistance, but little systematic evidence is available
about their objectives and choices in developing countries.
The authors develop two stylized accounts of NGO motivation:
one in which donor contracts determine location decisions,
and another in which altruistic motivations are the
principal determinants. The authors then use data from the
1995 and 2000 rounds of the Bangladesh Households and Income
and Expenditure Survey to analyze location decisions of NGO
programs established between those two sample years. The
data show that net change in a community's NGO program
was unrelated to the community's need and that NGOs
were ready to establish new programs in new areas without
being concerned of duplicating the efforts of other NGOs.
The findings suggest that contracts with donors, implicit or
explicit, probably play a crucial role in determining the
incentives that affect NGO program location choices
Location decisions and nongovernmental organization motivation : evidence from rural Bangladesh
No full textNongovernmental organizations (NGOs) play an increasingly important role in development assistance, but little systematic evidence is available about their objectives and choices in developing countries. The authors develop two stylized accounts of NGO motivation: one in which donor contracts determine location decisions, and another in which altruistic motivations are the principal determinants. The authors then use data from the 1995 and 2000 rounds of the Bangladesh Households and Income and Expenditure Survey to analyze location decisions of NGO programs established between those two sample years. The data show that net change in a community's NGO program was unrelated to the community's need and that NGOs were ready to establish new programs in new areas without being concerned of duplicating the efforts of other NGOs. The findings suggest that contracts with donors, implicit or explicit, probably play a crucial role in determining the incentives that affect NGO program location choices.Poverty Monitoring&Analysis,Insurance&Risk Mitigation,ICT Policy and Strategies,Poverty Impact Evaluation,Agricultural Knowledge&Information Systems,Poverty Monitoring&Analysis,Agricultural Knowledge&Information Systems,ICT Policy and Strategies,Non Governmental Organizations,Community Development and Empowerment
Inhibition of human placenta glutathione transferase P1-1 by calvatic acid
No full textThe inhibition mechanism of the dimeric human placenta glutathione transferase (GST P1-1) by the antibiotic p-carboxyphenylazoxycyanide (calvatic acid) has been investigated at pH 7.0 and 30.0 degrees C. Experiments performed at different calvatic acid/GST P1-1 molar ratios indicate that one mole of calvatic acid inactivates one mole of the homodimeric enzyme molecule, containing two catalytically equivalent active sites. The apparent second order rate constant for GST P1-1 inactivation is 2.4 +/- 0.3 M-1 s-1. The recovery of all the 5,5'-dithio-bis(2-nitro-benzoic acid)-titratable thiol groups as well as the original catalytic activity of GST P1-1 after treatment of the inhibited enzyme with dithiothreitol indicates that two disulfide bridges per dimer, likely between Cys47 and Cys101, have been formed during the reaction with calvatic acid. To the best of the authors knowledge, calvatic acid represents a unique case of enzyme inhibitor acting also throughout its reaction product(s)
The Strategic Choices of NGOs: Location Decisions in Rural Bangladesh
No full textNon-governmental organisations (NGOs) play an increasingly important role in the delivery of public services in developing countries, but little systematic evidence is available about their strategic choices. We develop two stylised accounts of NGO strategies: one in which pragmatic and organisational concerns determine location decisions, and another in which charitable motivations are the principal determinants. We then use data from the 1995 and 2000 rounds of the Bangladesh Household and Income and Expenditure Survey to analyse location decisions of NGO programmes established between those two sample years. Whether disaggregated by sector of work or mother organisation, the data show that the net change in NGO programmes in a community was not related to indicators of community need, that NGOs established new programmes where they themselves had no programmes previously, and that they did not avoid duplicating the efforts of other NGOs. Overall, the analysis is consistent with an account of NGO choices in which a concern for broad coverage significantly affects NGO choices.
Parental leave policies, intra-household time allocations and children’s human capital
No full textParental leave, Human capital investment, Income distribution, J1, J2,
Journal of Population Economics
No full textThis paper uses a general equilibrium model of marriage and divorce to assess how public policies on parental leave and leave benefits affect intra-household decision making, family structure, intergenerational mobility, and the distribution of income. The benchmark economy is calibrated to US data to replicate some characteristics relevant to the interaction between the marriage and labor markets. The effects of unpaid leave, paid leave benefits, and mandated leave on human capital investment, distribution of income, and welfare are then analyzed
Italo Calvino: um ponto de vista sobre o papel da tradução na obra literária
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Estudos da Tradução, Florianópolis, 2011Este trabalho tem como objetivo discutir o pensamento de Italo Calvino a respeito da tradução literária. Ele estuda especificamente as reflexões do autor sobre tradução, contidas em alguns de seus ensaios críticos selecionados para esta pesquisa, e também na metalinguagem do romance Se um viajante numa noite de inverno (1990). O que se quer é identificar e discutir quais são, na concepção do autor, as potencialidades e as limitações da tradução na sua relação com a literatura.The present work intends to discuss the thought of Italo Calvino concerning translation of literary works. It specifically studies the reflections of the author on translation as expressed in his critical essays selected for this research and in the metalinguistic novel If on a winter's night a traveler (1981). The main objective of this work is to identify and to discuss the author.s conceptions on potentials and limitations of translation in its relation with literature
Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide
No full textINTRODUCTION AND BACKGROUND:
Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors.
METHODS/DESIGN:
In this open label, multi-center, single-arm, Phase Ib/II, R/M-HNC patients pretreated with at least one line of therapy containing platinum, fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every other week until progression, and a single fraction of 8 Gy radiotherapy on day 8.
DISCUSSION:
The treatment protocol aims to reverse immune evasion of the tumor through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+ FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T-cell reactivation owing to the inhibition of the PD-1-PD-L1 axis by avelumab.The immunologic interplay induced by the proposed combined treatment may theoretically improve the activity of avelumab without increasing its toxicity profile.Finally, an ancillary translational study will be extended to all the patients' population.
TRIAL REGISTRATION:
EudraCT n. 2017-000353-39
