Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal alpha-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins - eIF5A(K56A) and eIF5A(Q22H,L93F)- and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression.

Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of reversed chloroquine (RCQ)

Reversed chloroquine (RCQ) is a multiple ligand compound active against chloroquine-sensitive and resistant falciparum malaria. It is composed by a 4-aminoquinoline moiety (like that present in chloroquine (CQ)) joined to imipramine (IMP), a modulating agent that also showed intrinsic antiplasmodial activity against Brazilian Plasmodium falciparum isolates resistant to CQ. Molecular modeling and ultraviolet-visible spectroscopy (UV-vis) studies strongly suggest that the interaction between RCQ and heme is predominant through the quinoline moiety in a mechanism of action similar to that observed for CQ. (C) 2010 Elsevier Ltd. All rights reserved.

Modeling and illustrating requirement prioritization in public e-service development from a value-based perspective

A major problem in e-service development is the prioritization of the requirements of different stakeholders. The main stakeholders are governments and their citizens, all of whom have different and sometimes conflicting requirements. In this paper, the prioritization problem is addressed by combining a value-based approach with an illustration technique. This paper examines the following research question: How can multiple stakeholder requirements be illustrated from a value-based perspective in order to be prioritizable? We used an e-service development case taken from a Swedish municipality to elaborate on our approach. Our contributions are: 1) a model of the relevant domains for requirement prioritization for government, citizens, technology, finances and laws and regulations; and 2) a requirement fulfillment analysis tool (RFA) that consists of a requirement-goal-value matrix (RGV), and a calculation and illustration module (CIM). The model reduces cognitive load, helps developers to focus on value fulfillment in e-service development and supports them in the formulation of requirements. It also offers an input to public policy makers, should they aim to target values in the design of e-services.

Modeling and forecasting long-term natural gas (NG) consumption in Iran, using particle swarm optimization (PSO)

The gradual changes in the world development have brought energy issues back into high profile. An ongoing challenge for countries around the world is to balance the development gains against its effects on the environment. The energy management is the key factor of any sustainable development program. All the aspects of development in agriculture, power generation, social welfare and industry in Iran are crucially related to the energy and its revenue. Forecasting end-use natural gas consumption is an important Factor for efficient system operation and a basis for planning decisions. In this thesis, particle swarm optimization (PSO) used to forecast long run natural gas consumption in Iran. Gas consumption data in Iran for the previous 34 years is used to predict the consumption for the coming years. Four linear and nonlinear models proposed and six factors such as Gross Domestic Product (GDP), Population, National Income (NI), Temperature, Consumer Price Index (CPI) and yearly Natural Gas (NG) demand investigated.

Healthcare providers balancing norms and practice : challenges and opportunities in providing contraceptive counselling to young people in Uganda - a qualitative study

BACKGROUND: Pregnancies among young women force girls to compromise education, resulting in low educational attainment with subsequent poverty and vulnerability. A pronounced focus is needed on contraceptive use, pregnancy, and unsafe abortion among young women. OBJECTIVE: This study aims to explore healthcare providers' (HCPs) perceptions and practices regarding contraceptive counselling to young people. DESIGN: We conducted 27 in-depth interviews with doctors and midwives working in seven health facilities in central Uganda. Interviews were open-ended and allowed the participant to speak freely on certain topics. We used a topic guide to cover areas topics of interest focusing on post-abortion care (PAC) but also covering contraceptive counselling. Transcripts were transcribed verbatim and data were analysed using thematic analysis. RESULTS: The main theme, HCPs' ambivalence to providing contraceptive counselling to sexually active young people is based on two sub-themes describing the challenges of contraceptive counselling: A) HCPs echo the societal norms regarding sexual practice among young people, while at the same time our findings B) highlights the opportunities resulting from providers pragmatic approach to contraceptive counselling to young women. Providers expressed a self-identified lack of skill, limited resources, and inadequate support from the health system to successfully provide appropriate services to young people. They felt frustrated with the consultations, especially when meeting young women seeking PAC. CONCLUSIONS: Despite existing policies for young people's sexual and reproductive health in Uganda, HCPs are not sufficiently equipped to provide adequate contraceptive counselling to young people. Instead, HCPs are left in between the negative influence of social norms and their pragmatic approach to address the needs of young people, especially those seeking PAC. We argue that a clear policy supported by a clear strategy with practical guidelines should be implemented alongside in-service training including value clarification and attitude transformation to equip providers to be able to better cater to young people seeking sexual and reproductive health advice.

August 1999: Financial Black Holes and Other Challenges

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Trade and poverty in latin american countries: conceptual and methodological challenges

This paper addresses topics - either relevant or confusing or needing more attention - related to measuring the trade and poverty nexus. It sheds a critical light on the existing material and suggests needed research lines. It starts with questions akin to the LAC realities; then, keeping this view, general methodological issues are also examined. In a broader perspective, further ideas for the research agenda are formulated. The main conclusion is that relevant findings still demand considerable efforts. Moreover, the Information-measurement-model-evaluation paradigm is not enough, policy guidelines being usually too general. In LAC, it must be extended and deepened, accounting more for the heterogeneity of cases, including, whenever possible, the physical constraints and incorporating new ways of integrating both the local and global perspectives. Other aspects, like the role of specific juridical measures, should play a role. How all this can be combined into more encompassing evaluations remains open

Modeling and predicting the CBOE market volatility index

This paper performs a thorough statistical examination of the time-series properties of the daily market volatility index (VIX) from the Chicago Board Options Exchange (CBOE). The motivation lies not only on the widespread consensus that the VIX is a barometer of the overall market sentiment as to what concerns investors' risk appetite, but also on the fact that there are many trading strategies that rely on the VIX index for hedging and speculative purposes. Preliminary analysis suggests that the VIX index displays long-range dependence. This is well in line with the strong empirical evidence in the literature supporting long memory in both options-implied and realized variances. We thus resort to both parametric and semiparametric heterogeneous autoregressive (HAR) processes for modeling and forecasting purposes. Our main ndings are as follows. First, we con rm the evidence in the literature that there is a negative relationship between the VIX index and the S&P 500 index return as well as a positive contemporaneous link with the volume of the S&P 500 index. Second, the term spread has a slightly negative long-run impact in the VIX index, when possible multicollinearity and endogeneity are controlled for. Finally, we cannot reject the linearity of the above relationships, neither in sample nor out of sample. As for the latter, we actually show that it is pretty hard to beat the pure HAR process because of the very persistent nature of the VIX index.

Open innovation and the challenges of human resource management

This paper considers challenges of Human Resource Management (HRM) in Open Innovation processes. It examines which strategies managers used to overcome these problems in the case of the Brazilian Oil and Gas company Petrobras. By conducting an inductive case study it develops a contextual model based on the use of grounded theory. It argues that the most important categories were to overcome problems of (a) the interpersonal relationship, (b) power shifting inside the organization, and (c) making people more valuable to the organization and shows how managers tackled these challenges. It contributes with a deep analysis of HRM challenges in Open Innovation that is important for a better understanding of management problems that can come along with Open Innovation processes.

Social entrepreneurship, microcredit and development challenges: a case study analysis of Banco Pérola

The term “social entrepreneurship” has been attracting growing interest from different sectors in the past years, driven by the possibility of employing business techniques to tackle recurrent social and environmental issues. At the forefront of this global phenomenon is microcredit, seen by many as an effective anti-poverty tool and having the Grameen Bank as its flagship program. While the prospects of social entrepreneurship seem promising, the newness of the concept and its somewhat confusing definition make conditions difficult to analyze this contemporary phenomenon. Therefore, the objective of this study was to discuss the challenges faced by social entrepreneurs and alternatives of development for social businesses through a case study on a Brazilian microcredit institution and inclusive business, Banco Pérola. The case addresses a growing need for case studies designed for teaching in the field of social entrepreneurship. It was focused mainly on understanding the development challenges within Banco Pérola, and built based on interviews carried out with top management, credit officer and clients of the institution, as well as on secondary data collected. An analysis of the case study was performed under a Teaching Notes. As illustrated by the Banco Pérola case, the main difficulties encountered by social entrepreneurs relate to the systematization of processes and creation of operational routines, including for performance evaluation (impact assessment tools); to the capture and management of both financial and human capital; to scaling up the business model and to the need of forging closer and more personal relationships with customers as against in traditional banking practices. In spite of certain limitations, such as the fact that the case might soon become outdated due to the fast-changing environment surrounding Banco Pérola, or the fact that not all relevant stakeholders (e.g. partners) were selected for interviews, the research objective has been achieved and the study can be seen as a contribution to spreading the concept of social entrepreneurship.

Transfer function-noise modeling and spatial interpolation to evaluate the risk of extreme (shallow) water-table levels in the Brazilian Cerrados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Signal transduction-related responses to phytohormones and environmental challenges in sugarcane

Background: Sugarcane is an increasingly economically and environmentally important C4 grass, used for the production of sugar and bioethanol, a low-carbon emission fuel. Sugarcane originated from crosses of Saccharum species and is noted for its unique capacity to accumulate high amounts of sucrose in its stems. Environmental stresses limit enormously sugarcane productivity worldwide. To investigate transcriptome changes in response to environmental inputs that alter yield we used cDNA microarrays to profile expression of 1,545 genes in plants submitted to drought, phosphate starvation, herbivory and N-2-fixing endophytic bacteria. We also investigated the response to phytohormones (abscisic acid and methyl jasmonate). The arrayed elements correspond mostly to genes involved in signal transduction, hormone biosynthesis, transcription factors, novel genes and genes corresponding to unknown proteins.Results: Adopting an outliers searching method 179 genes with strikingly different expression levels were identified as differentially expressed in at least one of the treatments analysed. Self Organizing Maps were used to cluster the expression profiles of 695 genes that showed a highly correlated expression pattern among replicates. The expression data for 22 genes was evaluated for 36 experimental data points by quantitative RT-PCR indicating a validation rate of 80.5% using three biological experimental replicates. The SUCAST Database was created that provides public access to the data described in this work, linked to tissue expression profiling and the SUCAST gene category and sequence analysis. The SUCAST database also includes a categorization of the sugarcane kinome based on a phylogenetic grouping that included 182 undefined kinases.Conclusion: An extensive study on the sugarcane transcriptome was performed. Sugarcane genes responsive to phytohormones and to challenges sugarcane commonly deals with in the field were identified. Additionally, the protein kinases were annotated based on a phylogenetic approach. The experimental design and statistical analysis applied proved robust to unravel genes associated with a diverse array of conditions attributing novel functions to previously unknown or undefined genes. The data consolidated in the SUCAST database resource can guide further studies and be useful for the development of improved sugarcane varieties.

Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal alpha-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins - eIF5A(K56A) and eIF5A(Q22H,L93F)- and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression.

Modeling and analysis of artificial neural networks applied in operations research

Artificial neural networks are dynamic systems consisting of highly interconnected and parallel nonlinear processing elements. Systems based on artificial neural networks have high computational rates due to the use of a massive number of these computational elements. Neural networks with feedback connections provide a computing model capable of solving a rich class of optimization problems. In this paper, a modified Hopfield network is developed for solving problems related to operations research. The internal parameters of the network are obtained using the valid-subspace technique. Simulated examples are presented as an illustration of the proposed approach. Copyright (C) 2000 IFAC.