Demand-based structural change and balanced economic growth

[eng] We analyze the equilibrium of a multi-sector exogenous growth model where the introduction of minimum consumption requirements drives structural change. We show that equilibrium dynamics simultaneously exhibt structural change and balanced growth of aggregate variables as is observed in US when the initial intensity of minimum consumption requirements is sufficiently small. This intensity is measured by the ratio between the aggregate value of the minimum consumption requirements and GDP and, therefore, it is inversely related with the level of economic development. Initially rich economies benefit from an initially low intensity of the minimum consumption requirements and, as a consequence, these economies end up exhibiting balanced growth of aggregate variables, while there is structural change. In contrast, initially poor economies suffer from an initially large intensity of the minimum consumption requirements, which makes the growth of the aggregate variables unbalanced during a very large period. These economies may never exhibit simultaneously balanced growth of aggregate variables and structural change.

Labor Mobility and Productivity Growth

[cat] Els models de creixement amb aprenentatge suposen que el coneixement après en producció es transmet de forma lliure i instantània a tota l'economia. En con- seqüència, l'economia presenta economies d'escala creixents i el creixement de la productivitat (TFP) és endògena. No obstant, el supòsit de difusió instantània del coneixement és poc realista. La difusió del coneixement necessita temps i algun canal de transmissió. En aquest article suposem que el coneixement es transmet amb la contractació de treballadors nous (learning-by-hiring). En el nostre model la difusió instantània i lliure de coneixement pot ocórrer només dins d'un sector. La difusió de coneixement entre sectors pot ocórrer només a través de la mobilitat de treballadors, i per tant, el mercat de treball determina el nivell i la taxa de creixement de productivitat (TFP). Estudiem com els costos de mobilitat laboral modifiquen l'equilibri sota dos escenaris: creixement endogen i exogen. A més, demostrem que d'altres ineficiències del mercat laboral, com són les taxes o els costos de cerca, poden reduir la mobilitat laboral, i per tant, modificar la TFP.

Labor Mobility and Productivity Growth

[cat] Els models de creixement amb aprenentatge suposen que el coneixement après en producció es transmet de forma lliure i instantània a tota l'economia. En con- seqüència, l'economia presenta economies d'escala creixents i el creixement de la productivitat (TFP) és endògena. No obstant, el supòsit de difusió instantània del coneixement és poc realista. La difusió del coneixement necessita temps i algun canal de transmissió. En aquest article suposem que el coneixement es transmet amb la contractació de treballadors nous (learning-by-hiring). En el nostre model la difusió instantània i lliure de coneixement pot ocórrer només dins d'un sector. La difusió de coneixement entre sectors pot ocórrer només a través de la mobilitat de treballadors, i per tant, el mercat de treball determina el nivell i la taxa de creixement de productivitat (TFP). Estudiem com els costos de mobilitat laboral modifiquen l'equilibri sota dos escenaris: creixement endogen i exogen. A més, demostrem que d'altres ineficiències del mercat laboral, com són les taxes o els costos de cerca, poden reduir la mobilitat laboral, i per tant, modificar la TFP.

Demand-based structural change and balanced economic growth

[eng] We analyze the equilibrium of a multi-sector exogenous growth model where the introduction of minimum consumption requirements drives structural change. We show that equilibrium dynamics simultaneously exhibt structural change and balanced growth of aggregate variables as is observed in US when the initial intensity of minimum consumption requirements is sufficiently small. This intensity is measured by the ratio between the aggregate value of the minimum consumption requirements and GDP and, therefore, it is inversely related with the level of economic development. Initially rich economies benefit from an initially low intensity of the minimum consumption requirements and, as a consequence, these economies end up exhibiting balanced growth of aggregate variables, while there is structural change. In contrast, initially poor economies suffer from an initially large intensity of the minimum consumption requirements, which makes the growth of the aggregate variables unbalanced during a very large period. These economies may never exhibit simultaneously balanced growth of aggregate variables and structural change.

Romanisation et vie quotidienne : le petiti mobilier de type italique en Gaule interne : (IIe s. av. J.-C.-Ier s. ap. J.-C.)

Durant les deux derniers siècles avant notre ère, des objets de type italique, c'est-à-dire caractérisant la culture matérielle de l'Italie tardo-républicaine apparaissent progressivement en Gaule. L'identification de ces objets du quotidien et leur analyse typologique et contextuelle permettent une approche renouvelée du phénomène de romanisation de la Gaule. L'objectif de cette thèse est de mettre en exergue les modalités chronologiques, spatiales et culturelles de la diffusion de ce type de mobilier. La confrontation des résultats avec les données issues des études céramologiques et architecturales permet de brosser un tableau affiné du processus d'acculturation. La nature des sites, ainsi que la diversité des types d'objets considérés permettent de souligner la variété des comportements des populations locales face à la réception de ces mobiliers exogènes. Que ce soit dans le commerce ou en intégrant l'armée romaine, les élites locales ont joué un rôle majeur au sein des interactions avec l'Italie, de la diffusion de ces objets et de l'intégration des nouveaux modèles italiques. -- For the last two centuries before our era, italic type objects, which means objects that are characterizing the material culture of Tardo-republican Italia, are progressively appearing in Gaul. The identification of these everyday objects and their typological and contextual analysis allow a renewed approach of the Gaul romanization phenomenon. The objective of this thesis is to highlight, the chronological, spatial and cultural modalities of the diffusion of such furniture. The comparison of the results with the data provided by the ceramological and architectural studies allows to improve the description of the acculturation process.The behavioral diversity towards the reception of exogenous furniture is underlined by the nature of the sites and the diversity of the considered objects. Local elites, whether by participating in commercial exchanges or by joining the army, have played a major role in the interactions with Italia, from the diffusion of these objects to the integration of the new italic models.

Phospholipid bilayer perturbing-properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of Nε- and Nα-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the α-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices.

Combinative effects of β-Lapachone and APO866 on pancreatic cancer cell death through reactive oxygen species production and PARP-1 activation.

UNLABELLED: Pancreatic cancer (PC) is one of the most lethal human malignancies and a major health problem. Patients diagnosed with PC and treated with conventional approaches have an overall 5-year survival rate of less than 5%. Novel strategies are needed to treat this disease. Herein, we propose a combinatorial strategy that targets two unrelated metabolic enzymes overexpressed in PC cells: NAD(P)H: quinone oxidoreductase-1 (NQO1) and nicotinamide phosphoribosyl transferase (NAMPT) using β-lapachone (BL) and APO866, respectively. We show that BL tremendously enhances the antitumor activity of APO866 on various PC cell lines without affecting normal cells, in a PARP-1 dependent manner. The chemopotentiation of APO866 with BL was characterized by the following: (i) nicotinamide adenine dinucleotide (NAD) depletion; (ii) catalase (CAT) degradation; (iii) excessive H2O2 production; (iv) dramatic drop of mitochondrial membrane potential (MMP); and finally (v) autophagic-associated cell death. H2O2 production, loss of MMP and cell death (but not NAD depletion) were abrogated by exogenous supplementation with CAT or pharmacological or genetic inhibition of PARP-1. Our data demonstrates that the combination of a non-lethal dose of BL and low dose of APO866 optimizes significantly cell death on various PC lines over both compounds given separately and open new and promising combination in PC therapy.

A case of suicide by self-injection of adrenaline.

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Role of basic calcium phosphate crystals in osteoarthritis

L'arthrose est une maladie dégénérative des articulations due à une dégradation progressive du cartilage. La calcification de l'articulation (essentiellement due à des dépôts de cristaux de phosphate de calcium basique -cristaux BCP-) est une caractéristique de cette maladie. Cependant, le rôle des cristaux BCP reste à déterminer. Nous avons tout d'abord déterminé en utilisant des cultures primaires de chondrocytes que les cristaux de BCP induisaient la production de la cytokine IL-6, via une signalisation intracellulaire implicant les kinase Syk, PI3 et Jak et Stat3. Les cristaux de BCP induisent également la perte de protéoglycanes et l'expression de IL-6 dans des explants de cartlage humain et ces deux effets peuvent être bloqués par un inhibiteur de IL-6, le Tocilizumab. Par ailleurs, nous avons trouvé que l'IL-6 ajouté à des chondrocytes, favorisait la formation de cristax de BCP et augmentait l'expression de gènes impliqués dans le processus de minéralisation : Ank (codant pour un transporteur de pyrophooshate), Annexin5 (codant pour un canal calcique) et Pit-1 (codant pour un transporteur de phoshate). In vivo, les cristaux de BCP injectés dans l'articulation de souris induisent une érosion du cartilage. Dans un modèle murin d'arthrose du genou induit par ménisectomie, nous avons observé la formation progressive de cristaux de BCP. Fait intéressant, la présence de ces cristaux dans l'articulation précédait la destruction du cartilage. Un agent susceptible de bloquer les calcifications tel que le sodium thiosulfate (STS), administré à des souris ménisectomisées, inhibait le dépôt intra-articulaire de ces cristaux ainsi que l'érosion du cartilage. Nous avons identifié ainsi un cercle vicieux dans l'arthrose, les cristaux induisant l'interleukine-6 et l'interleukine-6 induisant la formation de ces cristaux. Nous avons étudié si on pouvait bloquer cette boucle cristaux de BCP-IL6 soit par des agents décalcifiants, soit par des inhibiteurs d'IL-6. In vitro, des anticorps anti IL- 6 ou des inhibiteurs de signalisation, inhibaient significativement IL-6 et la minéralisation induite par IL-6. De même le STS inhibait la formation de ces cristaux et la production de l'IL-6. Tout récemment, nous avons trouvé que des inhibiteurs de la xanthine oxidoréductase étaient aussi capables d'inhiber à la fois la production d'IL-6 et la minéralization des chondrocytes. Finalement, nous avons pu exclure un rôle du système IL-1 dans le modèle d'arthrose induite par ménisectomie, les souris déficientes pour IL-1a/ß, MyD88 et l'inflammasome NLRP3 n'étant pas protégées dans ce modèle d'arthrose. L'ensemble de nos résultats montre que les cristaux BCP sont pathogéniques dans l'arthrose et qu'un inhibiteur de minéralisation tel que le STS ou un inhibiteur de l'interleukine-6 constitueraient des nouvelles thérapies pour l'arthrose. -- Osteoarthritis (OA), the most common degenerative disorder of the joints, results from an imbalance between the breakdown and repair of the cartilage and surrounding articular structures. Joint calcification (essentially due to basic calcium phosphate (BCP) crystal deposition) is a characteristic feature of OA. However, the role of BCP crystal deposition in the pathogenesis of OA remains unclear[1][1]. We first demonstrated that in primary murine chondrocytes exogenous BCP crystals led to IL-6 up-modulation and that BCP crystal signaling pathways involved Syk and PI3 kinases, and also gp130 associated molecules, Jak2 and Stat3. BCP crystals also induced proteoglycan loss and IL-6 expression in human cartilage expiants, (which were significantly reduced by an IL-6 inhibitor). In addition, we found that in chondrocytes exogenous IL-6 promoted calcium-containing crystal formation and up- regulation of genes codifying for proteins involved in the calcification process: the inorganic pyrophosphate transport channel Ank, the calcium channel Annexinö and the sodium/phosphate cotransporter Piti. In vivo, BCP crystals injected into murine knee joints induced cartilage erosion. In the menisectomy model, increasing deposits, identified as BCP crystals, were progressively observed around the joint before cartilage erosion. These deposits strongly correlated with cartilage degradation and IL-6 expression. These results demonstrated that BCP crystals deposition and IL-6 production are mutually reinforcing in the osteoarthritic pathogenic process. We then investigated if we could block the BCP-IL6 loop by either targeting IL-6 production or BCP crystal deposits. Treatment of chondrocytes with anti-IL-6 antibodies or inhibitors of IL-6- signaling pathway significantly inhibited IL-6-induced crystal formation. Similarly, sodium thiosulfate (STS), a well-known systemic calcification inhibitor, decreased crystal deposition as well as HA-induced IL-6 secretion in chondrocytes and, in vivo, it decreased crystal deposits size and cartilage erosion in menisectomized knees. Interestingly, we also found that xanthine-oxidoreductase (XO) inhibitors inhibited both IL-6 production and calcium crystal depositis in chondrocytes. We began to unravel the mechanisms involved in this coordinate modulation of IL-6 and mineralization. STS inhibited Reactive Oxygen Species (ROS) generation and we are currently investigating whether XO represents a major source of ROS in chondrocyte mineralization. Finally, we ruled out that IL-1 activation/signaling plays a role in the murine model of OA induced by menisectomy, as IL-1a/ß, the IL-1 R associated molecule MyD88 and NLRP3 inflammasome deficient mice were not protected in this model of OA. Moreover TLR-1, -2, -4,-6 deficient mice had a phenotype similar to that of wild-type mice. Altogether our results demonstrated a self-amplification loop between BCP crystals deposition and IL-6 production, which represents an aggravating process in OA pathogenesis. As currently prescribed OA drugs are addressing OA symptoms,our results highlight a potential novel treatment strategy whereby inhibitors of calcium- containing crystal formation and IL-6 could be combined to form the basis of a disease modifying treatment and alter the course of OA.

Endothelial Connexin37 and Connexin40 participate in basal but not agonist-induced NO release.

BACKGROUND: Connexin37 (Cx37) and Cx40 are crucial for endothelial cell-cell communication and homeostasis. Both connexins interact with endothelial nitric oxide synthase (eNOS). The exact contribution of these interactions to the regulation of vascular tone is unknown. RESULTS: Cx37 and Cx40 were expressed in close proximity to eNOS at cell-cell interfaces of mouse aortic endothelial cells. Absence of Cx37 did not affect expression of Cx40 and a 50 % reduction of Cx40 in Cx40(+/-) aortas did not affect the expression of Cx37. However, absence of Cx40 was associated with reduced expression of Cx37. Basal NO release and the sensitivity for ACh were decreased in Cx37(-/-) and Cx40(-/-) aortas but not in Cx40(+/-) aortas. Moreover, ACh-induced release of constricting cyclooxygenase products was present in WT, Cx40(-/-) and Cx40(+/-) aortas but not in Cx37(-/-) aortas. Finally, agonist-induced NO-dependent relaxations and the sensitivity for exogenous NO were not affected by genotype. CONCLUSIONS: Cx37 is more markedly involved in basal NO release, release of cyclooxygenase products and the regulation of the sensitivity for ACh as compared to Cx40.

New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.

Effects of unit - based pricing on the waste collection demand : a meta - regression analysis

We perform a meta - analysis of 21 studies that estimate the elasticity of the price of waste collection demand upon waste quantities, a prior literature review having revealed that the price elasticity differs markedly. Based on a meta - regression with a total of 65 observations, we find no indication that municipal data give higher estimates for price elasticities than those associated with household data. Furthermore, there is no evidence that treating prices as exogenous underestimates the price elasticity. We find that much of the variation can be explained by sample size, the use of a weight - based as opposed to a volume - based pricing system, and the pricing of compostable waste. We also show that price elasticities determined in the USA and point estimations of elasticities are more elastic, but these effects are not robust to the changing of model specifications. Finally, our tests show that there is no evidence of publication bias while there is some evidence of the existence of genuine empirical effect.

Forest Transition in Madagascar's Highlands: Initial Evidence and Implications

Madagascar is renowned for the loss of the forested habitat of lemurs and other species endemic to the island. Less well known is that in the highlands, a region often described as an environmental "basket-case" of fire-degraded, eroded grasslands, woody cover has been increasing for decades. Using information derived from publically available high- and medium-resolution satellites, this study characterizes tree cover dynamics in the highlands of Madagascar over the past two decades. Our results reveal heterogeneous patterns of increased tree cover on smallholder farms and village lands, spurred by a mix of endogenous and exogenous forces. The new trees play important roles in rural livelihoods, providing renewable supplies of firewood, charcoal, timber and other products and services, as well as defensible claims to land tenure in the context of a decline in the use of hillside commons for grazing. This study documents this nascent forest transition through Land Change Science techniques, and provides a prologue to political ecological analysis by setting these changes in their social and environmental context and interrogating the costs and benefits of the shift in rural livelihood strategies.

Mergers and difference-in-difference estimator : why firms do not increase prices?

Difference-in-Difference (DiD) methods are being increasingly used to analyze the impact of mergers on pricing and other market equilibrium outcomes. Using evidence from an exogenous merger between two retail gasoline companies in a specific market in Spain, this paper shows how concentration did not lead to a price increase. In fact, the conjectural variation model concludes that the existence of a collusive agreement before and after the merger accounts for this result, rather than the existence of efficient gains. This result may explain empirical evidence reported in the literature according to which mergers between firms do not have significant effects on prices.

Does evolution lead to maximizing behavior?

A long-standing question in biology and economics is whether individual organisms evolve to behave as if they were striving to maximize some goal function. We here formalize this "as if" question in a patch-structured population in which individuals obtain material payoffs from (perhaps very complex multimove) social interactions. These material payoffs determine personal fitness and, ultimately, invasion fitness. We ask whether individuals in uninvadable population states will appear to be maximizing conventional goal functions (with population-structure coefficients exogenous to the individual's behavior), when what is really being maximized is invasion fitness at the genetic level. We reach two broad conclusions. First, no simple and general individual-centered goal function emerges from the analysis. This stems from the fact that invasion fitness is a gene-centered multigenerational measure of evolutionary success. Second, when selection is weak, all multigenerational effects of selection can be summarized in a neutral type-distribution quantifying identity-by-descent between individuals within patches. Individuals then behave as if they were striving to maximize a weighted sum of material payoffs (own and others). At an uninvadable state it is as if individuals would freely choose their actions and play a Nash equilibrium of a game with a goal function that combines self-interest (own material payoff), group interest (group material payoff if everyone does the same), and local rivalry (material payoff differences).