"Pour charmer l'ennui de la route, Grétry, sa Lyre en main, traversait l'Achéron: Ramez donc, dit-il à Caron: Que faites-vous? ...J'écoute!" (P. Villiers)

Signatur des Originals: S 36/G04574

Kadesh-Barnea : its importance and probable site, with the story of a hunt for it, including studies of the route of the exodus and the southern boundary of the Holy Land

by H. Clay Trumbull

The Influence of Immunization Route on the Adjuvant Effect of alpha-Galactosylceramide

Potent vaccine formulations ideally include adjuvants to activate innate immune responses and enhance antigen-specific adaptive immunity. The synthetic glycolipid alpha-Galactosylceramide (α-GalCer) effectively activates the innate immune mediating NKT cells to produce cytokines and activate downstream immune cells, resulting in development of humoral and cell mediated immune responses to co-administered antigens. While a single intravenous immunization of α-GalCer strongly activates NKT cells, multiple doses by this route are well documented to induce anergy in NKT cells. Anergy is defined as the deficiency in NKT proliferation and cytokine production, including IL-4 and IFNγ. However, our studies have shown that two doses of α-GalCer administered intranasally by the intranasal route leads to reactivation of NKT cells and improved adaptive immune responses after each subsequent dose. I therefore investigated the role of multiple routes of immunization in activation of NKT cells, i.e. anergy versus repeated activation. Specifically, I hypothesized that the differential capacity of NKT cells to produce IFNγ, as a result of route of immunization with α-GalCer, influences the induction of adaptive immune responses to co-administered antigen. Our experimental design utilizes the observation that intranasal immunization primarily induces immune responses in the lungs while intravenous immunization induces responses in the liver. Using intracellular cytokine staining for IFNγ production and Elispot analyses for determining NKT and T cell activation, respectively, it was determined that administering two consecutive intravenous doses resulted in anergy to NKT cells (no IFNγ production) in the liver and lack of adaptive immunity while second immunization by the intranasal route overcame anergy in the lung. The outcome in the other tissues analyzed was mixed and could be the result of tissue microenvironment among others possible reasons. When intranasal dosing preceded systemic, NKT cells were reactivated to produce IFNγ and induced positive adaptive immune responses in the responding lung tissue. These results indicate that the mechanism by which mucosal and systemic immunization routes activate NKT cells may differ in that there is a differential tissue-specific effect induced by each route. Future studies are necessary to determine the reason for these tissue-specific effects and how they relate to NKT cell activation.

(Table 1) Contents of chlorophyll a over the Northern Sea Route according to data of field measurements and estimated from MODIS data on measurement days

New maps of mean monthly distribution of chlorophyll and primary production in the Kara Sea were compiled using joint processing of CZCS (1978-1986), SeaWiFS (1998-2005), and MODIS (2002-2006) satellite data and field measurements. The annual primary production of phytoplankton is estimated at 22.3 x 10**6 t C per year or 70 mg C/m**2 per day. Results of calculations of the organic carbon budget in the Kara Sea are presented.

Seawater carbonate chemistry and carbon allocation, growth and morphology of the coccolithophore Emiliania huxleyi (calcifying strain CCMP 371) during experiments, 2011

Coccolithophores are unicellular phytoplankton that produce calcium carbonate coccoliths as an exoskeleton. Emiliania huxleyi, the most abundant coccolithophore in the world's ocean, plays a major role in the global carbon cycle by regulating the exchange of CO2 across the ocean-atmosphere interface through photosynthesis and calcium carbonate precipitation. As CO2 concentration is rising in the atmosphere, the ocean is acidifying and ammonium (NH4) concentration of future ocean water is expected to rise. The latter is attributed to increasing anthropogenic nitrogen (N) deposition, increasing rates of cyanobacterial N2 fixation due to warmer and more stratified oceans, and decreased rates of nitrification due to ocean acidification. Thus future global climate change will cause oceanic phytoplankton to experience changes in multiple environmental parameters including CO2, pH, temperature and nitrogen source. This study reports on the combined effect of elevated pCO2 and increased NH4 to nitrate (NO3) ratio (NH4/NO3) on E. huxleyi, maintained in continuous cultures for more than 200 generations under two pCO2 levels and two different N sources. Here we show that NH4 assimilation under N-replete conditions depresses calcification at both low and high pCO2, alters coccolith morphology, and increases primary production. We observed that N source and pCO2 synergistically drive growth rates, cell size and the ratio of inorganic to organic carbon. These responses to N source suggest that, compared to increasing CO2 alone, a greater disruption of the organic carbon pump could be expected in response to the combined effect of increased NH4/NO3 ratio and CO2 level in the future acidified ocean. Additional experiments conducted under lower nutrient conditions are needed prior to extrapolating our findings to the global oceans. Nonetheless, our results emphasize the need to assess combined effects of multiple environmental parameters on phytoplankton biology in order to develop accurate predictions of phytoplankton responses to ocean acidification.

Ocean acidification induces multi-generational decline in copepod naupliar production with possible conflict for reproductive resource allocation

Climate change, including ocean acidification (OA), presents fundamental challenges to marine biodiversity and sustained ecosystem health. We determined reproductive response (measured as naupliar production), cuticle composition and stage specific growth of the copepod Tisbe battagliai over three generations at four pH conditions (pH 7.67, 7.82, 7.95, and 8.06). Naupliar production increased significantly at pH 7.95 compared with pH 8.06 followed by a decline at pH 7.82. Naupliar production at pH 7.67 was higher than pH 7.82. We attribute the increase at pH 7.95 to an initial stress response which was succeeded by a hormesis-like response at pH 7.67. A multi-generational modelling approach predicted a gradual decline in naupliar production over the next 100 years (equivalent to approximately 2430 generations). There was a significant growth reduction (mean length integrated across developmental stage) relative to controls. There was a significant increase in the proportion of carbon relative to oxygen within the cuticle as seawater pH decreased. Changes in growth, cuticle composition and naupliar production strongly suggest that copepods subjected to OA-induced stress preferentially reallocate resources towards maintaining reproductive output at the expense of somatic growth and cuticle composition. These responses may drive shifts in life history strategies that favour smaller brood sizes, females and perhaps later maturing females, with the potential to profoundly destabilise marine trophodynamics.

Experimental ocean acidification alters the allocation of metabolic energy

Energy is required to maintain physiological homeostasis in response to environmental change. Although responses to environmental stressors frequently are assumed to involve high metabolic costs, the biochemical bases of actual energy demands are rarely quantified. We studied the impact of a near-future scenario of ocean acidification [800 µatm partial pressure of CO2 (pCO2)] during the development and growth of an important model organism in developmental and environmental biology, the sea urchin Strongylocentrotus purpuratus. Size, metabolic rate, biochemical content, and gene expression were not different in larvae growing under control and seawater acidification treatments. Measurements limited to those levels of biological analysis did not reveal the biochemical mechanisms of response to ocean acidification that occurred at the cellular level. In vivo rates of protein synthesis and ion transport increased 50% under acidification. Importantly, the in vivo physiological increases in ion transport were not predicted from total enzyme activity or gene expression. Under acidification, the increased rates of protein synthesis and ion transport that were sustained in growing larvae collectively accounted for the majority of available ATP (84%). In contrast, embryos and prefeeding and unfed larvae in control treatments allocated on average only 40% of ATP to these same two processes. Understanding the biochemical strategies for accommodating increases in metabolic energy demand and their biological limitations can serve as a quantitative basis for assessing sublethal effects of global change. Variation in the ability to allocate ATP differentially among essential functions may be a key basis of resilience to ocean acidification and other compounding environmental stressors.

Seawater carbonate chemistry and resource allocation and extracellular acid-base status in the sea urchin Strongylocentrotus droebachiensis during experiments, 2012

Anthropogenic CO2 emission will lead to an increase in seawater pCO2 of up to 80-100 Pa (800-1000 µatm) within this century and to an acidification of the oceans. Green sea urchins (Strongylocentrotus droebachiensis) occurring in Kattegat experience seasonal hypercapnic and hypoxic conditions already today. Thus, anthropogenic CO2 emissions will add up to existing values and will lead to even higher pCO2 values >200 Pa (>2000 µatm). To estimate the green sea urchins' potential to acclimate to acidified seawater, we calculated an energy budget and determined the extracellular acid base status of adult S. droebachiensis exposed to moderately (102 to 145 Pa, 1007 to 1431 µatm) and highly (284 to 385 Pa, 2800 to 3800 µatm) elevated seawater pCO2 for 10 and 45 days. A 45 - day exposure to elevated pCO2 resulted in a shift in energy budgets, leading to reduced somatic and reproductive growth. Metabolic rates were not significantly affected, but ammonium excretion increased in response to elevated pCO2. This led to decreased O:N ratios. These findings suggest that protein metabolism is possibly enhanced under elevated pCO2 in order to support ion homeostasis by increasing net acid extrusion. The perivisceral coelomic fluid acid-base status revealed that S. droebachiensis is able to fully (intermediate pCO2) or partially (high pCO2) compensate extracellular pH (pHe) changes by accumulation of bicarbonate (maximum increases 2.5 mM), albeit at a slower rate than typically observed in other taxa (10 day duration for full pHe compensation). At intermediate pCO2, sea urchins were able to maintain fully compensated pHe for 45 days. Sea urchins from the higher pCO2 treatment could be divided into two groups following medium-term acclimation: one group of experimental animals (29%) contained remnants of food in their digestive system and maintained partially compensated pHe (+2.3 mM HCO3), while the other group (71%) exhibited an empty digestive system and a severe metabolic acidosis (-0.5 pH units, -2.4 mM HCO3). There was no difference in mortality between the three pCO2 treatments. The results of this study suggest that S. droebachiensis occurring in the Kattegat might be pre-adapted to hypercapnia due to natural variability in pCO2 in its habitat. We show for the first time that some echinoderm species can actively compensate extracellular pH. Seawater pCO2 values of >200 Pa, which will occur in the Kattegat within this century during seasonal hypoxic events, can possibly only be endured for a short time period of a few weeks. Increases in anthropogenic CO2 emissions and leakages from potential sub-seabed CO2 storage (CCS) sites thus impose a threat to the ecologically and economically important species S. droebachiensis.

How does credit access affect children's time allocation? Evidence from rural India

Using a unique dataset obtained from rural Andhra Pradesh, India that contains direct observations of household access to credit and detailed time use, results of this study indicate that credit market failures lead to a substantial reallocation of time used by children for activities such as schooling, household chores, remunerative work, and leisure. The negative effects of credit constraints on schooling amount to a 60% decrease of average schooling time. However, the magnitude of decrease due to credit constraints is about half that of the increase in both domestic and remunerative child labor, the other half appearing to come from a reduction in leisure.

Allocation efficiency in China : an extension of the dynamic Olley-Pakes productivity decomposition

This paper develops a quantitative measure of allocation efficiency, which is an extension of the dynamic Olley-Pakes productivity decomposition proposed by Melitz and Polanec (2015). The extended measure enables the simultaneous capture of the degree of misallocation within a group and between groups and parallel to capturing the contribution of entering and exiting firms to aggregate productivity growth. This measure empirically assesses the degree of misallocation in China using manufacturing firm-level data from 2004 to 2007. Misallocation among industrial sectors has been found to increase over time, and allocation efficiency within an industry has been found to worsen in industries that use more capital and have firms with relatively higher state-owned market shares. Allocation efficiency among three ownership sectors (state-owned, domestic private, and foreign sectors) tends to improve in industries wherein the market share moves from a less-productive state-owned sector to a more productive private sector.

Impact radiologique liés au transport de matières radioactives par route en Espagne / Radiological impact associated with the transport by road of radioactive material in Spain

Questions relating to the transport of radioactive materials are very much an issue of current interest due to the increasing mobility of the materials involved in the nuclear fuel cycle, commitment to the environment, the safety and protection of persons and the corresponding regulatory legal framework. The radiological impact associated with this type of transport was assessed by means of a new data-processing tool that may be of use and serve as complementary documentation to that included in transport regulations. Thus, by determining the level of radiation at a distance of one metre from the transport vehicle and by selecting a route, the associated impacts will be obtained, such as the affected populations, the dose received by the most highly exposed individual, the overall radiological impact, the doses received by the population along the route and the possible detriment to their health. The most important conclusion is that the emissions of ionising radiation from the transport of radioactive material by road in Spain are not significant as regards the generation of adverse effects on human health, and that their radiological impact may be considered negligible.

Comparative Analysis of Tolerances Allocation in Mechanical Assemblies based on Cost-tolerance Curves

El presente trabajo propone un método para la determinación de los valores de las tolerancias individuales de las piezas que forman un conjunto ensamblado a partir de valores de tolerancias especificados en el conjunto final, optimizando el coste total de fabricación de las piezas individuales a partir de funciones de coste-tolerancia basadas en el proceso de fabricación de cada una de ellas. Para ello se parte de los principales trabajos desarrollados en la línea de asignación de tolerancias y se realiza la propuesta del modelo de trabajo, basado en la optimización de costes a partir de la aplicación del método de los multiplicadores de Lagrange a diversas curvas de coste-tolerancia

IDRA (IDeal Resource Allocation): Computing ideal speedups in parallel logic programming

We present a technique to estimate accurate speedups for parallel logic programs with relative independence from characteristics of a given implementation or underlying parallel hardware. The proposed technique is based on gathering accurate data describing one execution at run-time, which is fed to a simulator. Alternative schedulings are then simulated and estimates computed for the corresponding speedups. A tool implementing the aforementioned techniques is presented, and its predictions are compared to the performance of real systems, showing good correlation.

IDRA (IDeal Resource Allocation): A tool for computing ideal speedups

Performance studies of actual parallel systems usually tend to concéntrate on the effectiveness of a given implementation. This is often done in the absolute, without quantitave reference to the potential parallelism contained in the programs from the point of view of the execution paradigm. We feel that studying the parallelism inherent to the programs is interesting, as it gives information about the best possible behavior of any implementation and thus allows contrasting the results obtained. We propose a method for obtaining ideal speedups for programs through a combination of sequential or parallel execution and simulation, and the algorithms that allow implementing the method. Our approach is novel and, we argüe, more accurate than previously proposed methods, in that a crucial part of the data - the execution times of tasks - is obtained from actual executions, while speedup is computed by simulation. This allows obtaining speedup (and other) data under controlled and ideal assumptions regarding issues such as number of processor, scheduling algorithm and overheads, etc. The results obtained can be used for example to evalúate the ideal parallelism that a program contains for a given model of execution and to compare such "perfect" parallelism to that obtained by a given implementation of that model. We also present a tool, IDRA, which implements the proposed method, and results obtained with IDRA for benchmark programs, which are then compared with those obtained in actual executions on real parallel systems.