Ángel Zabdiel Campos López | UNAM Universidad Nacional Autónoma de México (original) (raw)
Automotive Engineer by Ángel Zabdiel Campos López
Para generar una presión de inyección de 2000 bares se necesitan grandes fuerzas de accionamiento... more Para generar una presión de inyección de 2000 bares se necesitan grandes fuerzas de accionamiento. Estas fuerzas conducen a cargas intensas en los componentes del mando de distribución por correa dentada.
Appl Econ, 1997
ABSTRACT Methods are proposed for the estimation of equations for consumption categories subject ... more ABSTRACT Methods are proposed for the estimation of equations for consumption categories subject to non-participation and other types of censoring using an unbalanced panel data set on petrol expenditures from the Spanish Continuous Family Expenditure Survey. The use of panel data allows one to deal with two issues that pose econometric problems when dealing with individual budget data. On one hand, unobserved time invariant heterogeneity is controlled for. On the other hand, the problem of censoring in the dependent variable is addressed and the measurement error induced by infrequent purchases is corrected. Results suggest the use of probabilities of purchase estimated from the temporal pattern of expenditure records in order to carry out this correction. The estimated demand system is subsequently used to simulate the effects of changes in the taxation of petrol.
Feminism Amp Psychology, 2015
ABSTRACT The main question for consideration in this paper relates to the functional prerequisite... more ABSTRACT The main question for consideration in this paper relates to the functional prerequisites for the construction of the so-called ‘digital family’in the Spanish context. Taking inspiration from Burman's (1994; 2008) work we start from the assumptions, firstly, that representations of children and families are important in terms of power and gender and so that, secondly, when considering representations of the family we also, necessarily, address gender regulatory functions as much as economic and political trends. We argue that since the middle of the last decade reports on the Information Society show an unusual interest in children and their relations with Information and Communications Technology. In this context, we identify how enshrined in notions of the ‘digital family’ is a convergence of discourses on family and gender that refolds the family structure back in on itself, advocating a return to traditional values in much the same way as in previous eras.
Nuovo Cimento a Nucl Part F, 1995
The large N effective action of the non-linear sigma model based in the coset O(N+1)/O(N) is obta... more The large N effective action of the non-linear sigma model based in the coset O(N+1)/O(N) is obtained. The renormalization of this effective action requires the introduction of an infinite set of counterterms. However, there exit particular cases where, at some scale, only a finite number of non-zero coupling constants are present. This fact makes possible a one parameter fit of the I=J=0 low-energy pion scattering. The corresponding non-local effective action is used to study the properties of the skyrmion which is shown to be unstable in this approximation.
Investigaciones Economicas, Feb 1, 1994
Spanish Journal of Rural Development, 2013
Health Economics, Aug 1, 1998
In this paper we look at the behaviour of households as far as participation and rate of consumpt... more In this paper we look at the behaviour of households as far as participation and rate of consumption of tobacco are concerned using cohort data from the Spanish Continuous Family Expenditure Survey during the period 1985-94. We test the results, in statistical and economic terms, from several estimators on samples with different levels of aggregation and offer evidence on the different behaviour of households according to several demographic characteristics. The results suggest that the effect of legislative measures cannot be identified when participation and consumption are not separately considered. Once we do so, these measures seem to affect participation alone.
International Journal of Clinical and Health Psychology, 2013
Attention Deficit Hyperactivity Disorder (ADHD) is one of the disorders causing the greatest impa... more Attention Deficit Hyperactivity Disorder (ADHD) is one of the disorders causing the greatest impact, conditioning academic learning, quality of concentration, and capacity for self-regulation and control. The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV-TR) establishes the most commonly accepted criteria for diagnosis (Inattentive: ADHD-I, Hyperactive/impulsive: ADHD-HI, and Combined: ADHD-C), but currently, diverse studies disagree about whether to address it as a continuum with different degrees of intensity (subtype structure) or as specific disorders (counterposed profiles). Prior research has tested the hypothesis of differential categories with performance measures and cortical activation. The goal proposed herein is to confirm these results, incorporating a new measure, near-infrared hemoencefalography (nir-HEG), in order to control cortical activation through levels of blood oxygenation. For this purpose, we used a sample of 205 children between 8 and 13 years (105 control group, 28 with ADHD-I, 35 with ADHD-HI, and 37 with ADHD-C), administering a continuous performance test (TOVA), quantified electroencephalogram (Q-EEG), and nir-HEG. Results reflect the counterposed profiles hypothesis instead of the degrees of intensity, although the latter is more habitual and generalized.
Pharmacology, biochemistry, and behavior, Jan 10, 2015
Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has bee... more Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spin...
Proceedings of the National Academy of Sciences of the United States of America, Jan 26, 1999
Primitive subsets of leukemic cells isolated by using fluorescence-activated cell sorting from pa... more Primitive subsets of leukemic cells isolated by using fluorescence-activated cell sorting from patients with newly diagnosed Ph(+)/BCR-ABL(+) chronic myeloid leukemia display an abnormal ability to proliferate in vitro in the absence of added growth factors. We now show from analyses of growth-factor gene expression, protein production, and antibody inhibition studies that this deregulated growth can be explained, at least in part, by a novel differentiation-controlled autocrine mechanism. This mechanism involves the consistent and selective activation of IL-3 and granulocyte colony-stimulating factor (G-CSF) production and a stimulation of STAT5 phosphorylation in CD34(+) leukemic cells. When these cells differentiate into CD34(-) cells in vivo, IL-3 and G-CSF production declines, and the cells concomitantly lose their capacity for autonomous growth in vitro despite their continued expression of BCR-ABL. Based on previous studies of normal cells, excessive exposure of the most prim...
![Research paper thumbnail of Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]](https://attachments.academia-assets.com/54691941/thumbnails/1.jpg)
](Critical care (London, England), 2004
This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety... more This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia. Intubated cardiac, general postsurgical or medical patients (aged >/= 18 years), who were mechanically ventilated for 12-72 hours, received remifentanil (9 microgram/kg per hour; n = 77) or fentanyl (1.5 microgram/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation-Agitation Scale score of 4). The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation-Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those...
PLoS Biology, 2013
The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth fact... more The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML) cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting such pathways in cancer.
Current Topics in Developmental Biology, 2005
Tyrosine and serine phosphorylation are central to cellular signaling in growth and development. ... more Tyrosine and serine phosphorylation are central to cellular signaling in growth and development. 14-3-3 proteins function as dimeric phosphoserine-binding proteins with documented interactions throughout the eukaryotic proteome and are highly conserved in both the animal and plant kingdoms. Binding of 14-3-3 to a client protein can have a range of context-dependent effects, including conformational change, enzyme inhibition, a shielding effect, re-localization, and bridging between two molecules. Proteome-based strategies utilizing mass spectrometry have revealed an unprecedented central stage for 14-3-3 in signal transduction with interacting partners composing at least 0.6% of the cellular proteome. 14-3-3 has been shown to bind to the human GM-CSF, IL-3, and IL-5 receptors and is required for the transmission of cell survival. 14-3-3 is involved in survival-specific signals, acting not only at the receptor level but also at critical steps downstream of the receptor. This phosphoserine-mediated pathway works independently of tyrosine kinases, highlighting an alternative mechanism of signaling for this receptor family. Other growth factor receptors and their adaptors are also being shown to associate with 14-3-3 and/or have putative 14-3-3 interaction sequences, such as the prolactin receptor, IGF-1 receptor, and some G-protein coupled receptors. 14-3-3 proteins are remarkably conserved through eukaryotic organisms and in Drosophila are required for photoreceptor development, learning, timing of cell cycles, and maintenance of cellular polarity. These findings are elevating our initial description of biochemical interactions to a better understanding of 14-3-3 function at the level of the whole organism. Further study should explore the integration of phosphoserine and phosphotyrosine signaling by 14-3-3 proteins and the role of isoform-specific functions in higher organisms. The prevalence of functional 14-3-3 binding sites throughout the proteome, and especially among growth factor receptors and signaling molecules, reflects a global role for 14-3-3 in multiple cellular decision making.
Atención Primaria, 2014
In the past few decades, increasing pharmaceutical expenditures in Spain and other western countr... more In the past few decades, increasing pharmaceutical expenditures in Spain and other western countries led to the adoption of reforms in order to reduce this trend. The aim of our study was to analyze if reforms concerning the pharmaceutical reimbursement scheme in Spain have been associated with changes in the volume and trend of pharmaceutical consumption. Retrospective observational study. Region of Murcia. Prescription drug in primary care and external consultations. Records of prescribed medicines between January 1, 2008 and December 31, 2013. Segmented regression analysis of interrupted time-series of prescription drug consumption. Dispensing of all five therapeutic classes fell immediately after co-payment changes. The segmented regression model suggested that per patient drug consumption in pensioners may have decreased by about 6.76% (95% CI; -8.66% to -5.19%) in the twelve months after the reform, compared with the absence of such a policy. Furthermore the slope of the series of consumption increased from 6.08 (P<.001) to 12.17…
Transplant International, 2007
Para generar una presión de inyección de 2000 bares se necesitan grandes fuerzas de accionamiento... more Para generar una presión de inyección de 2000 bares se necesitan grandes fuerzas de accionamiento. Estas fuerzas conducen a cargas intensas en los componentes del mando de distribución por correa dentada.
Appl Econ, 1997
ABSTRACT Methods are proposed for the estimation of equations for consumption categories subject ... more ABSTRACT Methods are proposed for the estimation of equations for consumption categories subject to non-participation and other types of censoring using an unbalanced panel data set on petrol expenditures from the Spanish Continuous Family Expenditure Survey. The use of panel data allows one to deal with two issues that pose econometric problems when dealing with individual budget data. On one hand, unobserved time invariant heterogeneity is controlled for. On the other hand, the problem of censoring in the dependent variable is addressed and the measurement error induced by infrequent purchases is corrected. Results suggest the use of probabilities of purchase estimated from the temporal pattern of expenditure records in order to carry out this correction. The estimated demand system is subsequently used to simulate the effects of changes in the taxation of petrol.
Feminism Amp Psychology, 2015
ABSTRACT The main question for consideration in this paper relates to the functional prerequisite... more ABSTRACT The main question for consideration in this paper relates to the functional prerequisites for the construction of the so-called ‘digital family’in the Spanish context. Taking inspiration from Burman's (1994; 2008) work we start from the assumptions, firstly, that representations of children and families are important in terms of power and gender and so that, secondly, when considering representations of the family we also, necessarily, address gender regulatory functions as much as economic and political trends. We argue that since the middle of the last decade reports on the Information Society show an unusual interest in children and their relations with Information and Communications Technology. In this context, we identify how enshrined in notions of the ‘digital family’ is a convergence of discourses on family and gender that refolds the family structure back in on itself, advocating a return to traditional values in much the same way as in previous eras.
Nuovo Cimento a Nucl Part F, 1995
The large N effective action of the non-linear sigma model based in the coset O(N+1)/O(N) is obta... more The large N effective action of the non-linear sigma model based in the coset O(N+1)/O(N) is obtained. The renormalization of this effective action requires the introduction of an infinite set of counterterms. However, there exit particular cases where, at some scale, only a finite number of non-zero coupling constants are present. This fact makes possible a one parameter fit of the I=J=0 low-energy pion scattering. The corresponding non-local effective action is used to study the properties of the skyrmion which is shown to be unstable in this approximation.
Investigaciones Economicas, Feb 1, 1994
Spanish Journal of Rural Development, 2013
Health Economics, Aug 1, 1998
In this paper we look at the behaviour of households as far as participation and rate of consumpt... more In this paper we look at the behaviour of households as far as participation and rate of consumption of tobacco are concerned using cohort data from the Spanish Continuous Family Expenditure Survey during the period 1985-94. We test the results, in statistical and economic terms, from several estimators on samples with different levels of aggregation and offer evidence on the different behaviour of households according to several demographic characteristics. The results suggest that the effect of legislative measures cannot be identified when participation and consumption are not separately considered. Once we do so, these measures seem to affect participation alone.
International Journal of Clinical and Health Psychology, 2013
Attention Deficit Hyperactivity Disorder (ADHD) is one of the disorders causing the greatest impa... more Attention Deficit Hyperactivity Disorder (ADHD) is one of the disorders causing the greatest impact, conditioning academic learning, quality of concentration, and capacity for self-regulation and control. The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV-TR) establishes the most commonly accepted criteria for diagnosis (Inattentive: ADHD-I, Hyperactive/impulsive: ADHD-HI, and Combined: ADHD-C), but currently, diverse studies disagree about whether to address it as a continuum with different degrees of intensity (subtype structure) or as specific disorders (counterposed profiles). Prior research has tested the hypothesis of differential categories with performance measures and cortical activation. The goal proposed herein is to confirm these results, incorporating a new measure, near-infrared hemoencefalography (nir-HEG), in order to control cortical activation through levels of blood oxygenation. For this purpose, we used a sample of 205 children between 8 and 13 years (105 control group, 28 with ADHD-I, 35 with ADHD-HI, and 37 with ADHD-C), administering a continuous performance test (TOVA), quantified electroencephalogram (Q-EEG), and nir-HEG. Results reflect the counterposed profiles hypothesis instead of the degrees of intensity, although the latter is more habitual and generalized.
Pharmacology, biochemistry, and behavior, Jan 10, 2015
Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has bee... more Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spin...
Proceedings of the National Academy of Sciences of the United States of America, Jan 26, 1999
Primitive subsets of leukemic cells isolated by using fluorescence-activated cell sorting from pa... more Primitive subsets of leukemic cells isolated by using fluorescence-activated cell sorting from patients with newly diagnosed Ph(+)/BCR-ABL(+) chronic myeloid leukemia display an abnormal ability to proliferate in vitro in the absence of added growth factors. We now show from analyses of growth-factor gene expression, protein production, and antibody inhibition studies that this deregulated growth can be explained, at least in part, by a novel differentiation-controlled autocrine mechanism. This mechanism involves the consistent and selective activation of IL-3 and granulocyte colony-stimulating factor (G-CSF) production and a stimulation of STAT5 phosphorylation in CD34(+) leukemic cells. When these cells differentiate into CD34(-) cells in vivo, IL-3 and G-CSF production declines, and the cells concomitantly lose their capacity for autonomous growth in vitro despite their continued expression of BCR-ABL. Based on previous studies of normal cells, excessive exposure of the most prim...
Critical care (London, England), 2004
This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety... more This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia. Intubated cardiac, general postsurgical or medical patients (aged >/= 18 years), who were mechanically ventilated for 12-72 hours, received remifentanil (9 microgram/kg per hour; n = 77) or fentanyl (1.5 microgram/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation-Agitation Scale score of 4). The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation-Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those...
PLoS Biology, 2013
The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth fact... more The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML) cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting such pathways in cancer.
Current Topics in Developmental Biology, 2005
Tyrosine and serine phosphorylation are central to cellular signaling in growth and development. ... more Tyrosine and serine phosphorylation are central to cellular signaling in growth and development. 14-3-3 proteins function as dimeric phosphoserine-binding proteins with documented interactions throughout the eukaryotic proteome and are highly conserved in both the animal and plant kingdoms. Binding of 14-3-3 to a client protein can have a range of context-dependent effects, including conformational change, enzyme inhibition, a shielding effect, re-localization, and bridging between two molecules. Proteome-based strategies utilizing mass spectrometry have revealed an unprecedented central stage for 14-3-3 in signal transduction with interacting partners composing at least 0.6% of the cellular proteome. 14-3-3 has been shown to bind to the human GM-CSF, IL-3, and IL-5 receptors and is required for the transmission of cell survival. 14-3-3 is involved in survival-specific signals, acting not only at the receptor level but also at critical steps downstream of the receptor. This phosphoserine-mediated pathway works independently of tyrosine kinases, highlighting an alternative mechanism of signaling for this receptor family. Other growth factor receptors and their adaptors are also being shown to associate with 14-3-3 and/or have putative 14-3-3 interaction sequences, such as the prolactin receptor, IGF-1 receptor, and some G-protein coupled receptors. 14-3-3 proteins are remarkably conserved through eukaryotic organisms and in Drosophila are required for photoreceptor development, learning, timing of cell cycles, and maintenance of cellular polarity. These findings are elevating our initial description of biochemical interactions to a better understanding of 14-3-3 function at the level of the whole organism. Further study should explore the integration of phosphoserine and phosphotyrosine signaling by 14-3-3 proteins and the role of isoform-specific functions in higher organisms. The prevalence of functional 14-3-3 binding sites throughout the proteome, and especially among growth factor receptors and signaling molecules, reflects a global role for 14-3-3 in multiple cellular decision making.
Atención Primaria, 2014
In the past few decades, increasing pharmaceutical expenditures in Spain and other western countr... more In the past few decades, increasing pharmaceutical expenditures in Spain and other western countries led to the adoption of reforms in order to reduce this trend. The aim of our study was to analyze if reforms concerning the pharmaceutical reimbursement scheme in Spain have been associated with changes in the volume and trend of pharmaceutical consumption. Retrospective observational study. Region of Murcia. Prescription drug in primary care and external consultations. Records of prescribed medicines between January 1, 2008 and December 31, 2013. Segmented regression analysis of interrupted time-series of prescription drug consumption. Dispensing of all five therapeutic classes fell immediately after co-payment changes. The segmented regression model suggested that per patient drug consumption in pensioners may have decreased by about 6.76% (95% CI; -8.66% to -5.19%) in the twelve months after the reform, compared with the absence of such a policy. Furthermore the slope of the series of consumption increased from 6.08 (P<.001) to 12.17…
Transplant International, 2007
Current Opinion in Structural Biology, 2012
Cytokines are well recognized for the pleiotropic nature of their signaling and biological activi... more Cytokines are well recognized for the pleiotropic nature of their signaling and biological activities on many cell types and their role in health and disease. Recent years have seen a steady stream of new cytokine receptor crystal structures including those that are activated by GM-CSF, type I interferon, and a variety of interleukins. Highlights include the observation of a dodecameric signaling complex for the GM-CSF receptor, electron microscopy imaging of an intact gp130/IL-6/IL-6Ra ternary receptor complex bound to its signal transducing Janus kinase and visualization of novel cytokine recognition mechanisms in the interleukin-17 and type I interferon families. This increasing knowledge in cytokine structural biology is driving new opportunities for developing novel therapies to modulate cytokine function in a diverse range of diseases including malignancies and chronic inflammation. 4 These authors made equal contributions. 5 Joint senior authors.
European Transactions on Electrical Power, 2011
We study the impact of electricity divestments in a stylised model where a dominant producer face... more We study the impact of electricity divestments in a stylised model where a dominant producer faces a competitive fringe with the same cost structure and is forced to sell some of its capacity. For a given demand level, the divestment which achieves the greatest reduction in prices can be several times more effective in reducing prices than a divestment of baseload (or low-cost) plants. We extend this theoretical result to the case with variable electricity demand by considering a numerical example based on data from the Italian market.
SSRN Electronic Journal, 2000
Page 1. Electronic copy available at: http://ssrn.com/abstract=1440157 IESE Business School-Unive... more Page 1. Electronic copy available at: http://ssrn.com/abstract=1440157 IESE Business School-University of Navarra - 1 FORECLOSING COMPETITION THROUGH ACCESS CHARGES AND PRICE DISCRIMINATION Ángel L. López Patrick Rey ...
The Economic Journal, 2014
ABSTRACT We re-examine the literature on mobile termination in the presence of network externalit... more ABSTRACT We re-examine the literature on mobile termination in the presence of network externalities. Externalities arise when firms discriminate between on- and off-net calls or when subscription demand is elastic. This literature predicts that profit decreases and consumer surplus increases in termination charge in a neighborhood of termination cost. This creates a puzzle since in reality we see regulators worldwide pushing termination rates down while being opposed by network operators. We show that this puzzle is resolved when consumers� expectations are assumed passive but required to be fulfilled in equilibrium (as defined by Katz and Shapiro, AER 1985), instead of being rationally responsive to non-equilibrium prices, as assumed until now.
Medicina Paliativa, 2013
Recibido el 10 de marzo de 2011; aceptado el 17 de noviembre de 2011 Disponible en Internet el 20... more Recibido el 10 de marzo de 2011; aceptado el 17 de noviembre de 2011 Disponible en Internet el 20 de marzo de 2012
Growth Factors, 2012
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pluripotent cytokine produced by m... more Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pluripotent cytokine produced by many cells in the body, which regulates normal and malignant hemopoiesis as well as innate and adaptive immunity. GM-CSF assembles and activates its heterodimeric receptor complex on the surface of myeloid cells, initiating multiple signaling pathways that control key functions such as cell survival, cell proliferation, and functional activation. Understanding the molecular composition of these pathways, the interaction of the various components as well as the kinetics and dose-dependent mechanics of receptor activation provides valuable insights into the function of GM-CSF as well as the related cytokines, interleukin-3 and interleukin-5. This knowledge provides opportunities for the development of new therapies to block the action of these cytokines in hematological malignancy and chronic inflammation.
Teknokultura Revista De Cultura Digital Y Movimientos Sociales, Jan 9, 2014
Los grandes avances tecnológicos de nuestro siglo implican también un desarrollo de las capacidad... more Los grandes avances tecnológicos de nuestro siglo implican también un desarrollo de las capacidades de vigilancia inimaginable hace dos décadas. La digitalización de prácticamente todas las comunicaciones deja pocos espacios de acción e interacción social al margen de la mediación tecnológica. Como resulta evidente, la infraestructura de telecomunicaciones no está diseñada para garantizar la privacidad y el secreto de las comunicaciones y actividades personales, sino para potenciar la capacidad centralizada de vigilancia.
Immunological Reviews, 2012
Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are mem... more Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are members of a discrete family of cytokines that regulates the growth, differentiation, migration and effector function activities of many hematopoietic cells and immunocytes. These cytokines are involved in normal responses to infectious agents, bridging innate and adaptive immunity. However, in certain cases, the overexpression of these cytokines or their receptors can lead to excessive or aberrant initiation of signaling resulting in pathological conditions, with chronic inflammatory diseases and myeloid leukemias the most notable examples. Recent crystal structures of the GM-CSF receptor ternary complex and the IL-5 binary complex have revealed new paradigms of cytokine receptor activation. Together with a wealth of associated structure-function studies, they have significantly enhanced our understanding of how these receptors recognize cytokines and initiate signals across cell membranes. Importantly, these structures provide opportunities for structure-based approaches for the discovery of novel and disease-specific therapeutics. In addition, recent biochemical evidence has suggested that the GM-CSF/IL-3/IL-5 receptor family is capable of interacting productively with other membrane proteins at the cell surface. Such interactions may afford additional or unique biological activities and might be harnessed for selective modulation of the function of these receptors in disease.
Cytokine & Growth Factor Reviews, 2013
The GM-CSF, IL-3 and IL-5 family of cytokines, also known as the βc family due to their receptors... more The GM-CSF, IL-3 and IL-5 family of cytokines, also known as the βc family due to their receptors sharing the signalling subunit βc, regulates multiple biological processes such as native and adaptive immunity, inflammation, normal and malignant hemopoieis, and autoimmunity. Australian scientists played a major role in the discovery and biological characterisation of the βc cytokines and their recent work is revealing unique features of cytokine receptor assembly and signalling. Furthermore, specific antibodies have been generated to modulate their function. Characterisation of the structural and dynamic requirements for the activation of the βc receptor family and the molecular definition of downstream signalling pathways are providing new insights into cytokine receptor signalling as well as new therapeutic opportunities.
Insect Biochemistry and Molecular Biology, 2007
In addition to its wide role in metabolism, iron in insects has been implicated in vitellogenesis... more In addition to its wide role in metabolism, iron in insects has been implicated in vitellogenesis and the immune response. The NRAMP family comprises a well-conserved family of divalent cation transporters in metazoans. To gain insight on the role of NRAMP in Anopheles albimanus, we cloned a cDNA encoding a 571-residue protein (AnaNRAMP) with the structural features defining the NRAMP family. AnaNRAMP mRNA induced 59 Fe 2+ incorporation when injected into Xenopus oocytes. Western blot analysis revealed that AnaNRAMP is expressed in the head, midgut and at high levels in Malpighian tubules of unfed female mosquito. Upon blood feeding, AnaNRAMP levels were reduced in the midgut whereas they increased in the Malpighian tubules. Using immunolocalization by transmission electron microscopy, AnaNRAMP was localized in the membrane of the intra-cellular concretions or spherites of the Malpighian tubule principal cells. Taken together, our results suggest an important role of AnaNRAMP in iron transport and indicate a role of the mosquito Malpighian tubule as an important organ for iron homeostasis. r
Cellular Signalling, 2010