bluuebunny/crossref_metadata_2025 huggingface dataset:
How Many Have Died from Undiagnosed Human Immunodeficiency Virus–Associated Histoplasmosis, A Treatable Disease? Time to Act
Authors: Nacher Mathieu , Adenis Antoine , Aznar Christine , Blanchet Denis , Vantilcke Vincent , Demar Magalie , Carme Bernard , Couppié Pierre
Published: November 2013

Human immunodeficiency virus (HIV)–associated disseminated Histoplasma capsulatum capsulatum infection often mimics tuberculosis. This disease is well know in the United States but is dramatically underdiagnosed in Central and South America. In the Amazon region, given the available incidence data and the regional HIV prevalence, it is expected that, every year, 1,500 cases of histoplasmosis affect HIV patients in that region alone. Given the mortality in undiagnosed patients, at least 600 patients would be expected to die from an undiagnosed but treatable disease. The lack of a simple diagnostic tool and the lack of awareness by clinicians spiral in a vicious cycle and made a major problem invisible for 30 years. The HIV/acquired immunodeficiency syndrome community should tackle this problem now to prevent numerous avoidable deaths from HIV-associated histoplasmosis in the region and elsewhere.
Strategic Incentives in Teams: Implications of Returns to Scale
Authors: McGinty Matthew
Published: November 2013

This article demonstrates the critical relationship between the characteristics of the production function and the strategic incentives in a team. Equilibrium effort increases in team size when substitutability is low relative to returns to scale. Effort levels are actually strategic complements when returns to scale exceed the substitutability of members' effort. Moreover, even with equal shares the well‐known problem is determined by returns to scale and becomes worse as returns increase. While a target scheme can support the optimal output level as an equilibrium, it does not completely deter free riding. A team member will accommodate shirking by increasing their own effort within a remarkably large “accommodation zone” where the additional effort cost is less than the bonus. This accommodation of shirking by others exists for different returns to scale and even for very low levels of substitutability.
High-resolution chemical ionization mass spectrometry (ToF-CIMS): application to study SOA composition and processing
Authors: Aljawhary D. , Lee A. K. Y. , Abbatt J. P. D.
Published: November 2013

Abstract. This paper demonstrates the capabilities of chemical ionization mass spectrometry (CIMS) to study secondary organic aerosol (SOA) composition with a high-resolution (HR) time-of-flight mass analyzer (aerosol-ToF-CIMS). In particular, by studying aqueous oxidation of water-soluble organic compounds (WSOC) extracted from α-pinene ozonolysis SOA, we assess the capabilities of three common CIMS reagent ions: (a) protonated water clusters (H2O)nH+, (b) acetate CH3C(O)O− and (c) iodide water clusters I(H2O)n− to monitor SOA composition. Furthermore, we report the relative sensitivity of these reagent ions to a wide range of common organic aerosol constituents. We find that (H2O)nH+ is more selective to the detection of less oxidized species, so that the range of O / C and OSC (carbon oxidation state) in the SOA spectra is considerably lower than those measured using CH3C(O)O− and I(H2O)n−. Specifically, (H2O)nH+ ionizes organic compounds with OSC ≤ 1.3, whereas CH3C(O)O− and I(H2O)n− both ionize highly oxygenated organics with OSC up to 4 with I(H2O)n− being more selective towards multi-functional organic compounds. In the bulk O / C and H / C space (in a Van Krevelen plot), there is a remarkable agreement in both absolute magnitude and oxidation trajectory between ToF-CIMS data and those from a high-resolution aerosol mass spectrometer (HR-AMS). Despite not using a sensitivity-weighted response for the ToF-CIMS data, the CIMS approach appears to capture much of the chemical change occurring. As demonstrated by the calibration experiments with standards, this is likely because there is not a large variability in sensitivities from one highly oxygenated species to another, particularly for the CH3C(O)O− and I(H2O)n− reagent ions. Finally, the data illustrate the capability of aerosol-ToF-CIMS to monitor specific chemical change, including the fragmentation and functionalization reactions that occur during organic oxidation, and the oxidative conversion of dimeric SOA species into monomers. Overall, aerosol-ToF-CIMS is a valuable, selective complement to some common SOA characterization methods, such as AMS and spectroscopic techniques. Both laboratory and ambient SOA samples can be analyzed using the techniques illustrated in the paper.
Remote sensing of a NTC radio source from a Cluster tilted spacecraft pair
Authors: Décréau P. M. E. , Kougblénou S. , Lointier G. , Rauch J.-L. , Trotignon J.-G. , Vallières X. , Canu P. , Rochel Grimald S. , El-Lemdani Mazouz F. , Darrouzet F.
Published: November 2013

Abstract. The Cluster mission operated a "tilt campaign" during the month of May 2008. Two of the four identical Cluster spacecraft were placed at a close distance (~50 km) from each other and the spin axis of one of the spacecraft pair was tilted by an angle of ~46°. This gave the opportunity, for the first time in space, to measure global characteristics of AC electric field, at the sensitivity available with long boom (88 m) antennas, simultaneously from the specific configuration of the tilted pair of satellites and from the available base of three satellites placed at a large characteristic separation (~1 RE). This paper describes how global characteristics of radio waves, in this case the configuration of the electric field polarization ellipse in 3-D-space, are identified from in situ measurements of spin modulation features by the tilted pair, validating a novel experimental concept. In the event selected for analysis, non-thermal continuum (NTC) waves in the 15–25 kHz frequency range are observed from the Cluster constellation placed above the polar cap. The observed intensity variations with spin angle are those of plane waves, with an electric field polarization close to circular, at an ellipticity ratio e = 0.87. We derive the source position in 3-D by two different methods. The first one uses ray path orientation (measured by the tilted pair) combined with spectral signature of magnetic field magnitude at source. The second one is obtained via triangulation from the three spacecraft baseline, using estimation of directivity angles under assumption of circular polarization. The two results are not compatible, placing sources widely apart. We present a general study of the level of systematic errors due to the assumption of circular polarization, linked to the second approach, and show how this approach can lead to poor triangulation and wrong source positioning. The estimation derived from the first method places the NTC source region in the dawn sector, at a large L value (L ~ 10) and a medium geomagnetic latitude (35° S). We discuss these untypical results within the frame of the geophysical conditions prevailing that day, i.e. a particularly quiet long time interval, followed by a short increase of magnetic activity.
Short Communication: Humans and the missing C-sink: erosion and burial of soil carbon through time
Authors: Hoffmann T. , Mudd S. M. , van Oost K. , Verstraeten G. , Erkens G. , Lang A. , Middelkoop H. , Boyle J. , Kaplan J. O. , Willenbring J. , Aalto R.
Published: November 2013

Abstract. Is anthropogenic soil erosion a sink or source of atmospheric carbon? The answer depends on factors beyond hillslope erosion alone because the probable fate of mobilized soil carbon evolves as it traverses the fluvial system. The transit path, residence times, and the resulting mechanisms of C-loss or gain change significantly down-basin and are currently difficult to predict as soils erode and floodplains evolve – this should be a key focus of future research.
Assessing the influence of sea walls on the coastal vulnerability of a pinned, soft-cliff, sandy coastline
Authors: Barkwith A. , Hurst M. D. , Thomas C. W. , Ellis M. A. , Limber P. W. , Murray A. B.
Published: November 2013

Abstract. Coastal defences have long been employed to halt or slow coastal erosion. Their impact on local sediment flux and ecology has been studied in detail through field studies and numerical simulations. The non-local impact of a modified sediment flux regime on mesoscale erosion and accretion has received less attention. Morphological changes at this scale due to defended structures can be difficult to quantify or identify with field data. Engineering scale numerical models, often applied to assess the design of modern defences on local coastal erosion, tend not to cover large stretches of coast and are rarely applied to assess the impact of older structures. We extend previous work to explore the influences of sea walls on the evolution and morphological sensitivity of a pinned, soft-cliff, sandy coastline under a changing wave climate. The Holderness coast of East Yorkshire, UK, is used as a case study, represented both as a defended example with major sea walls included and a natural example where no sea defences exist. Using a mesoscale numerical coastal evolution model, stochastic wave climate data are perturbed gradually to assess the sensitivity of the coastal morphology to changing wave climate for both the defended and natural scenarios. Comparative analysis of the simulated output suggests that sea walls in the south of the region have a greater impact on sediment flux due to the increased sediment availability along this part of the coast. Multiple defended structures, including those separated by several kilometres, were found to interact with each other, producing a complex imprint on coastal morphology under a changing wave climate. Although spatially and temporally heterogeneous, sea walls generally slowed coastal recession and accumulated sediment on their up-drift side.
Interaction of valleys and circulation patterns (CPs) on spatial precipitation patterns in southern Germany
Authors: Liu M. , Bárdossy A. , Zehe E.
Published: November 2013

Abstract. Topography exerts influence on the spatial precipitation distribution over different scales, known typically at the large scale as the orographic effect, and at the small scale as the wind-drift rainfall (WDR) effect. At the intermediate scale (1~10 km), which is characterized by secondary mountain valleys, topography also demonstrates some effect on the precipitation pattern. This paper investigates such intermediate-scale topographic effects on precipitation patterns, focusing on narrow-steep valleys in the complex terrain of southern Germany, based on the daily observations over a 48 yr period (1960~2007) from a high-density rain-gauge network covering two sub-areas, Baden-Wuerttemberg (BW) and Bavaria (BY). Precipitation data at the valley and non-valley stations are compared under consideration of the daily general circulation patterns (CPs) classified by a fuzzy rule-based algorithm. Scatter plots of precipitation against elevation demonstrate a different behavior of valley stations comparing to non-valley stations. A detailed study of the precipitation time series for selected station triplets, each consisting of a valley station, a mountain station and an open station have been investigated by statistical analysis with the Kolmogorov–Smirnov (KS) test supplemented by the One-way analysis of variance (One-way ANOVA) and a graphical comparison of the mean precipitation amounts. The results show an interaction of valley orientation and the direction of the CPs at the intermediate scale, i.e. when the valley is shielded from the CP which carries the precipitation, the precipitation amount within the valley is comparable to that on the mountain crest, and both larger than the precipitation at the open station. When the valley is open to the CP, the precipitation within the valley is similar to the open station but much less than that on the mountain. Such phenomenon where the precipitation is "blind" to the valleys at the intermediate scale conditioned on CPs is defined as the "narrow-valley effect" in this work. Such an effect cannot be captured by the widely used elevation–precipitation relationship, which implies that the traditional geostatistical interpolation schemes, e.g. ordinary kriging (OK) or external drift kriging (EDK) applying digital elevation model (DEM) as external information, are not sufficient. An interpolation experiment applying EDK with orographic surrogate elevation defined in this paper as auxiliary information to account for the valley effects shows improvement for the cross-validation.
Improvement in the Geofencing Service Interface Using Indoor Positioning Systems and Mobile Sensors
Authors: Nakagawa M.
Published: November 2013

Abstract. The current state of location-based services provides spatial information delivery for mobile users based on position data taken from GPS sensors. However, sometimes the spatial information delivery service includes unwanted information. In particular, push-based or passive information delivery has a high probability that users receive unwanted information. We propose a new spatial information delivery to improve the integrity of spatial information delivery. We conducted an experiment using an Indoor Messaging System and an accelerometer, and concluded that our methodology can detect user behavior without accessing personal information and reduce the amount of spam information.
Automated high resolution 3D reconstruction of cultural heritage using multi-scale sensor systems and semi-global matching
Authors: Wohlfeil J. , Strackenbrock B. , Kossyk I.
Published: November 2013

Abstract. 3D surface models with high resolution and high accuracy are of great value in many applications, especially if these models are true to scale. As a promising alternative to active scanners (light section, structured light, laser scanners, etc.) new photogrammetric approaches are coming up. They use modern structure from motion (SfM) techniques, using the camera as main sensor. Unfortunately, the accuracy and resolution achievable with the available tools is very limited. When reconstructing large objects with high resolution an unacceptably high laborious effort is another problem. This paper shows an approach to overcome these limitations. It combines the strengths of modern surface reconstruction techniques from the remote sensing sector with novel SfM technologies, resulting in accurate 3D models of indoor and outdoor scenes. Starting with the image acquisition all particular steps to a final 3D model are explained. Finally the results of the evaluation of the approach at different indoor scenes are presented.
Tuber yield and leaf mineral composition of Jerusalem artichoke (Helianthus tuberosus L.) grown under different cropping practices
Authors: Rodrigues M.A. , Sousa L. , Cabanas J.E. , Arrobas M.
Published: November 2013

Jerusalem artichoke is commonly grown for its edible tubers, livestock feed and as an ornamental. The possibility of growing Jerusalem artichoke for energetic purposes has aroused scientific interest in this species. Despite several studies that have already been done in the last few decades, many aspects of the cropping practice are still relatively unknown. During the growing seasons of 2004-2006 field trials were carried out in NE Portugal. In the experimental period different cropping conditions were imposed, regarding planting density, N fertilization and propagation method. The crop was irrigated in 2004 and 2005 and grown in rain-fed conditions in 2006. The planting densities were 7 plants/square m in 2004, 2, 3 and 4 plants/square m in 2005 and 2 and 4 plants/square m in 2006. Botanical-seed was used in 2005 and seedtubers in all the three years. In 2005, 0 and 100 kg N/ha was combined in a factorial design with the planting densities. The maximum tuber dry matter yield was 18.4 Mg/ha (65.6 Mg/ha, fresh weight basis) and it was recorded in 2005 in the plots where 100 kg N/ha, 2 plants/square m and seed-tubers were combined. The best planting density was 2 plants/square m in irrigated (2005) and rain-fed (2006) conditions. Nitrogen significantly increased tuber yield in 2005 only when seed-tubers were used. Averaged across N fertilization rates and planting densities mean tuber dry matter yields were 12.8 and 6.9 Mg/ha for seed-tuber and botanical-seed, respectively. Leaf mineral composition was little affected by cropping practices. The "Bragança" clone showed high tuber yield potential, although the mean weight of the individual tubers was low which could make mechanization of the harvest difficult. The poor results achieved with botanicalseed argue against its use as an alternative to the seed-tubers.
Agronomic response of maize to limited levels of water under furrow irrigation in southern Spain
Authors: Aguilar M. , Borjas F. , Espinosa M.
Published: November 2013

The yield response to limited irrigation is a major concern where water resources are limited. The objective of the work was to know the agronomic response of 12 maize hybrids cultivars under full and limited irrigation levels. Full irrigation consisted in 5 to 7 furrow irrigations events (90 mm) applying a total depth of 450-630 mm. In the limited irrigation treatment, three irrigations (90 mm) were applied, beginning 2-3 weeks before silking and ending 3-5 weeks after it. Results indicated a mean yield loss of 17% due to limited irrigation. The main effect of limited irrigation was a reduction of the ears per plant and 1,000 kernel weight. Maize yield decreased as season length was reduced. The main effect of season length reduction was a reduction of kernels per ear. Limited or regulated deficit irrigation is one way of maximizing productivity of total applied water (PAW); thus, the limited irrigation treatment reached a higher PAW value (2.66 kg/cubic m) than full irrigation (1.90 kg/cubic m). In both irrigation levels, PAW was higher as the growth cycle increased. It can be concluded that, in the conditions of Southern Spain, reduced irrigation provided larger yields when applied to long cycle cultivars (FAO 700-800), with increased PAW values.
Influence of spacing on the initial production of hedgerow ‘Arbequina’ olive orchards
Authors: León L. , De la Rosa R. , Rallo L. , Guerrero N. , Barranco D.
Published: November 2013

A new type of olive (Olea europaea L.) orchard, based on high-density hedgerows harvested by vineyard type straddleharvesters has appeared in recent years. This system greatly simplifies olive harvesting, which has a high labour demand in standard olive orchards. There are, however, no specific low-vigour olive cultivars or dwarfing rootstocks adapted to this system, as exist in other fruit crops. It is therefore crucial to select the optimum density for maximum production without causing serious competition problems. In this study we present initial results of the effect of densities, ranging from 780 to 2,580 olive trees ha-1, on the production of an ‘Arbequina’ olive hedgerow orchard during the first seven years after planting. There were no significant differences in fruit characteristics (oil content and moisture) among density treatments. Density had a linear negative influence on fruit yield tree-1. In contrast, accumulated yield ha-1, for both fruit and oil yield, showed a linear increase with increased density, with coefficients of determination ranging from 0.37 to 0.72. Accumulated oil yield at high density was up to 5,000 kg ha-1 more than at the low density
Genetic parameters for litter size and weight at different parities in Iberian pigs
Authors: Fernández A. , Rodrigáñez J. , Zuzúarregui J. , Rodríguez M.C. , Silió L.
Published: November 2013

Genetic progress for reproductive performance in pigs is limited by mothering ability. It is a critical aspect for dam lines, in which litter weight at weaning could be included with litter size in the selection goal. Our objective was to investigate in Iberian pigs the genetic basis of the number of alive born piglets (NBA) and the litter weight at 21days (LW21) over the successive parities (t). Records for NBA were available from 6,775 litters born from 1,893 sows of the Torbiscal line, and LW21 records proceeded from 1,431 sows and 2,963 litters without crossfostering. Genetic parameters were estimated using an animal model with repeatability, a multi-trait animal model, and a random regression model. Estimated values of heritabilities for NBA and genetic correlations between parities confirm a partially different genetic control of prolificacy at parity 1 and at later parities. Results for LW21 indicate that this trait may be partially controlled by different genes at the first two parities and at the later ones. Estimated genetic parameters for NBA (t = 1), NBA (t >/= 2), LW21 (t /= 3) were: heritability, hE2 = 0.15, 0.12, 0.22 and 0.15, respectively, and coefficient of permanent environmental effects, pE2 = 0.05, 0.02 and 0.24, respectively for the three last traits. The values of genetic correlations ranged from 0.44 to 0.84. A multitrait approach would be useful to estimate accurate genetic parameters, and to improve the low persistency of reproductive performance in the later parities of Iberian sows.
Rapid evolution of the population of begomoviruses associated with the tomato yellow leaf curl disease after invasion of a new ecological niche: a review
Authors: Moriones E. , Navas-Castillo J.
Published: November 2013

Epidemics of tomato yellow leaf curl disease (TYLCD) caused by monopartite begomoviruses (family Geminiviridae) result in devastating damage to tomato (Solanum lycopersicum L.) crops in Spain since early 1990's. Initially, the ES strain of the species Tomato yellow leaf curl Sardinia virus (TYLCSV) was reported as the causal agent. The population of this virus exhibited a high genetic stability. However, introduction of new virus types also associated with TYLCD occurred which rapidly altered the virus population structure and diversity. Thus, isolates of the Mld and the IL strains of Tomato yellow leaf curl virus (TYLCV) were introduced, which resulted in a progressive displacement of TYLCSV. Single, undifferentiated subpopulations were observed for each virus type, compatible with founder effects. Mixed infections were detected in single plants, rationalizing the occurrence of recombinants. In fact, natural recombinants between TYLCSV and TYLCV with selective advantage over the parental genotypes rapidly emerged and spread in the virus population. These data evidenced the great dynamism of the begomovirus population associated with the TYLCD after the invasion of a non-native area and the contribution of genetic migration and recombination to the genetic diversification.
The degree of plant resilience to infection correlates with virus virulence and host-range
Authors: Agueldo Romero P. , Elena S.F.
Published: November 2013

Antagonistic interactions between plant viruses and their host lead to coevolution of virus virulence and host defenses. Plant virus adaptation to the defenses of a specific host may occur in detriment of their ability to exploit alternative hosts, driving to specialization. Using comparative analyses of the symptoms induced by members of several families of RNA plant viruses and of a quantitative estimate of the susceptibility to viral infection of plant families, it is shown that viral families that infect hosts from different families (generalists) exploited them in a benign way. Furthermore, plants infected by generalist viruses showed, on average, a large susceptibility to infection. By contrast, viral families parasitizing a small number of hosts from very few families (specialists) exploited them more virulently. Plants hosting very virulent and specialized viruses are also less susceptible to viral infection. Finally, it has been shown that specialist viruses are, on average, more virulent than generalists ones.
New trends in rabbit feeding: influence of nutrition on intestinal health. A review
Authors: Carabaño R. , Badiola I. , Chamorro S. , García J. , García-Ruiz A. I. , García-Rebollar P. , Gómez-Conde M. S. , Gutiérrez I. , Nicodemus N. , Villamide M. J. , De Blas J. C.
Published: November 2013

The role of gut barrier against pathogens and its interaction with dietary factors in weaned rabbits affected with digestive disorders, especially epizootic rabbit enteropathy is reviewed. This interaction was studied identifying nutritive factors that influence gut barrier function of mucosa. It was examined the morphology, and enzyme activity of mucosa and the gut associated immune system. Besides, it was characterized the substrate that reaches the caecum and its capacity to favour pathogen bacteria growth, by reviewing the effect of diet on ileal digestibility of nutrients, transit time and microbiota population. The nutritional factors which affect health of early weaned rabbits are level and type of both fibre and protein. The optimal dietary level of insoluble fibre to minimise mortality is 30-32%. Furthermore, a moderate inclusion of soluble fibre (12%) improves mucosa integrity and decreases mortality and the frequency of detection of Clostridium perfringens and Campylobacter spp in the caecum. The reduction of ileal nitrogen flow had a positive effect on pups viability and frequency of detection of C. perfringens. Furthermore, dietary supplementation with 1% of glutamine reduced fattening mortality, the frequency of detection of C. perfringens, and Helicobacter spp, and diminished the counts of Eimeria spp at the jejunum. In conclusion, a correct diet formulation may help to limit the epizootic rabbit enteropathy incidence in weaned rabbits.
Media and Cognition
Authors: de la Fosse Sébastien ,   Philosophy Documentation Center
Published: November 2013

While throughout history, knowledge and information have been mostly bound in language and text, new twenty-first-century media increasingly tend to break with this tradition of linear sequentiality. This paper will present an account of how this development may be explained by a relationship between the use of digital technologies on the one hand, and the (human) user’s cognitive processes on the other. This will be done by, first, outlining two existing conceptions of human cognition and, subsequently, by confronting these with observations in the field of philosophy of media, most prominently the position of Marshall McLuhan.
Adapting to change: Water utility financial practices in the early twenty‐first century
Authors: Boyle Christine E.
Published: November 2013

Water and wastewater utility managers are encountering a host of financial challenges beyond their control. From the recent economic recession to the health of financial markets, aging infrastructure, and a changing climate, complex issues threaten utilities' financial health. Many water utilities are responding to address these challenges. To date, few studies have examined how widespread innovative financial practices are among the nation's public water systems and how these practices are helping utilities cope with mounting financial challenges. This article examines the major financial challenges facing water utilities and reviews the current state of the US water sector's financial management practices with the aim of strengthening policymakers' understanding of the drivers and impacts of available financial mechanisms. Utility financial practices are evaluated on the basis of their ability to minimize risk and create financial resilience in utility financial management.
Entre métropole et régions, un même raisonnement peut-il soutenir un choix de modèles de services différent pour l’intégration des élèves allophones ?
Authors: De Koninck Zita , Armand Françoise
Published: November 2013

Dans de nombreux pays, les milieux scolaires font face à de grands défis d’intégration des élèves nouvellement arrivés ou issus de l’immigration. Au coeur de ces défis se situe celui du choix des modèles de services à offrir à ces élèves dont la langue d’origine n’est pas celle de l’institution d’accueil. Le but de cet article sera de présenter les résultats d’une enquête portant sur les modèles de services de soutien à l’intégration mis en place à l’intérieur de l’école publique québécoise dans la région du Grand Montréal ou ailleurs à Québec et en région, et de rendre compte de la manière dont des intervenants appartenant à des milieux différents soutiennent, en faisant pourtant appel à une argumentation similaire, le choix de modèles de services distincts pour assurer la réussite de l’intégration.
Early Paleogene evolution of terrestrial climate in the SW Pacific, Southern New Zealand
Authors: Pancost Richard D. , Taylor Kyle W. R. , Inglis Gordon N. , Kennedy Elizabeth M. , Handley Luke , Hollis Christopher J. , Crouch Erica M. , Pross Jörg , Huber Matthew , Schouten Stefan , Pearson Paul N. , Morgans Hugh E. G. , Raine J. Ian
Published: November 2013

We present a long‐term record of terrestrial climate change for the Early Paleogene of the Southern Hemisphere that complements previously reported marine temperature records. Using the MBT′‐CBT proxy, based on the distribution of soil bacterial glycerol dialkyl glycerol tetraether lipids, we reconstructed mean annual air temperature (MAT) from the Middle Paleocene to Middle Eocene (62–42 Ma) for southern New Zealand. This record is consistent with temperature estimates derived from leaf fossils and palynology, as well as previously published MBT′‐CBT records, which provides confidence in absolute temperature estimates. Our record indicates that through this interval, temperatures were typically 5°C warmer than those of today at such latitudes, with more pronounced warming during the Early Eocene Climate Optimum (EECO; ∼50 Ma) when MAT was ∼20°C. Moreover, the EECO MATs are similar to those determined for Antarctica, with a weak high‐latitude terrestrial temperature gradient (∼5°C) developing by the Middle Eocene. We also document a short‐lived cooling episode in the early Late Paleocene when MAT was comparable to present. This record corroborates the trends documented by sea surface temperature (SST) proxies, although absolute SSTs are up to 6°C warmer than MATs. Although the high‐calibration error of the MBT′‐CBT proxy dictates caution, the good match between our MAT results and modeled temperatures supports the suggestion that SST records suffer from a warm (summer?) bias, particularly during times of peak warming.
The deep permafrost carbon pool of the Yedoma region in Siberia and Alaska
Authors: Strauss Jens , Schirrmeister Lutz , Grosse Guido , Wetterich Sebastian , Ulrich Mathias , Herzschuh Ulrike , Hubberten Hans‐Wolfgang
Published: November 2013

Estimates for circumpolar permafrost organic carbon (OC) storage suggest that this pool contains twice the amount of current atmospheric carbon. The Yedoma region sequestered substantial quantities of OC and is unique because its deep OC, which was incorporated into permafrost during ice age conditions. Rapid inclusion of labile organic matter into permafrost halted decomposition and resulted in a deep long‐term sink. We show that the deep frozen OC in the Yedoma region consists of two distinct major subreservoirs: Yedoma deposits (late Pleistocene ice‐ and organic‐rich silty sediments) and deposits formed in thaw‐lake basins (generalized as thermokarst deposits). We quantified the OC pool based on field data and extrapolation using geospatial data sets to 83 + 61/−57 Gt for Yedoma deposits and to 128 + 99/−96 Gt for thermokarst deposits. The total Yedoma region 211 + 160/−153 Gt is a substantial amount of thaw‐vulnerable OC that must be accounted for in global models.
Seismic evidence for thermal runaway during intermediate‐depth earthquake rupture
Authors: Prieto Germán A. , Florez Manuel , Barrett Sarah A. , Beroza Gregory C. , Pedraza Patricia , Blanco Jose Faustino , Poveda Esteban
Published: November 2013

Intermediate‐depth earthquakes occur at depths where temperatures and pressures exceed those at which brittle failure is expected. There are two leading candidates for the physical mechanism behind these earthquakes: dehydration embrittlement and self‐localizing thermal shear runaway. A complete energy budget for a range of earthquake sizes can help constrain whether either of these mechanisms might play a role in intermediate‐depth earthquake rupture. The combination of high stress drop and low radiation efficiency that we observe for Mw 4–5 earthquakes in the Bucaramanga Nest implies a temperature increase of 600–1000°C for a centimeter‐scale layer during earthquake failure. This suggests that substantial shear heating, and possibly partial melting, occurs during intermediate‐depth earthquake failure. Our observations support thermal shear runaway as the mechanism for intermediate‐depth earthquakes, which would help explain differences in their behavior compared to shallow earthquakes.
Realistic initiation and dynamics of the Madden‐Julian Oscillation in a coarse resolution aquaplanet GCM
Authors: Ajayamohan R. S. , Khouider Boualem , Majda Andrew J.
Published: November 2013

The main mechanisms for the initiation and propagation of the Madden‐Julian Oscillation (MJO) are still widely debated. The capacity of operational global climate models (GCMs) to correctly simulate the MJO is hindered by the inadequacy of the underlying cumulus parameterizations. Here we show that a coarse resolution GCM, coupled to a simple multicloud model parameterization mimicking the observed dynamics and physical structure of organized tropical convection, simulates the MJO in an idealized setting of an aquaplanet without ocean dynamics. We impose a fixed nonhomogeneous sea‐surface temperature replicating the Indian Ocean/Western Pacific warm pool. This results in a succession of MJOs with realistic phase speed, amplitude, and physical structure. Each MJO event is initiated at a somewhat random location over the warm pool and dies sometimes near the eastern boundary of the warm pool and sometimes at a random location way beyond the warm pool. Also occasionally the MJO events stall at the center of maximum heating. This is reminiscent of the fact that in nature some MJOs stall over the maritime continent while others reach the central Pacific Ocean and beyond. The initiation mechanism in the model is believed to be a combination of persistent intermittent convective events interacting with observed large‐scale flow patterns and internal tropical dynamics. The large‐scale flow patterns are associated with planetary‐scale dry Kelvin waves that are triggered by preceding MJO events and circle the globe, while congestus cloud decks on the flanks of the warm pool are believed to force Rossby gyres which then funnel moisture toward the equatorial region.
Estimating tropical cyclone precipitation risk in Texas
Authors: Zhu Laiyin , Quiring Steven M. , Emanuel Kerry A.
Published: November 2013

This paper uses a new rainfall algorithm to simulate the long‐term tropical cyclone precipitation (TCP) climatology in Texas based on synthetic tropical cyclones generated from National Center for Atmospheric Research/National Centers for Environmental Prediction reanalysis data from 1980 to 2010. The synthetic TCP climatology shows good agreement with the available observations with respect to TCP return periods, especially for daily and event TCP. Areas within 200 km of the coast have higher TCP risk with two hot spots located near Houston and Corpus Christi. Based on this technique, there are locations in Texas where a TCP event > 1000 mm has a return period of 500 years and a TCP event > 1400 mm has a return period of 1000 years. There is a high degree of spatial heterogeneity in TCP risk in central Texas due to the topography.
Long‐term observations of the quasi two‐day wave by Hawaii MF radar
Authors: Gu Sheng‐Yang , Li Tao , Dou Xiankang , Wang Ning‐Ning , Riggin Dennis , Fritts David
Published: November 2013

A mesospheric horizontal wind data set measured during 1991–2006 by the medium frequency (MF) radar at Kauai, Hawaii (22°N, 160°W) is analyzed to examine the long‐term variability of the quasi two‐day wave (QTDW). The QTDW over Hawaii is amplified twice a year, with the January and July events most likely being the representation of zonal wave numbers 3 and 4 modes, respectively. The amplitudes of the January monthly mean QTDW in both meridional and zonal winds and the July monthly mean QTDW in meridional component are nearly in phase with the solar cycle but with the solar maxima leading the QTDW maxima by 1 or 2 years. However, the July monthly mean QTDW in zonal wind is more antiphase with the solar cycle. Enhanced QTDW oscillations are evident in both wind components in January 1998, which is likely related to the strong El Niño event during the winter of 1997/1998. The enhanced gravity wave activity and the increased barotropic/baroclinic/inertial instability related to the strengthened stratosphere summer easterly jet might provide additional forcing to amplify the QTDW. Moreover, the enhanced migrating diurnal tide during warm El Niño‐Southern Oscillation events could also contribute to the abnormally strong QTDW by increasing the refractive index and thus the growth rate of the QTDW. Additional enhancement of the QTDW with a short period of ~43 h is observed during the major sudden stratospheric warming in January 2006.
Deep water renewal in Lake Baikal: A model for long‐term analyses
Authors: Piccolroaz Sebastiano , Toffolon Marco
Published: November 2013

The phenomenon of deep water renewal in the South Basin of Lake Baikal is investigated by means of a simplified one‐dimensional model. The downwelling process, whereby large volumes of superficial, cold, and oxygenated water periodically sink to the lake bottom (
) due to thermobaric instability, is simulated by means of three main submodules: a reaction‐diffusion equation for temperature and other tracers, and two Lagrangian algorithms, the first for the vertical stabilization of unstable density regions (including thermobaric effects) and the second handling the downwelling mechanism. A self‐consistent procedure for the dynamical reconstruction of the diapycnal diffusivity profile is included to account for the effect of the variability of external conditions. The model has been developed aimed at providing a detailed description of deep‐ventilation and a quantification of its consequences at the basin scale; the core algorithms have been designed suitably to perform long‐term simulations (hundreds of years) and to deal with a limited amount of information about boundary conditions, which are expressed in terms of wind forcing and surface water temperature. The main parameters have been calibrated using measured profiles of temperature and chlorofluorocarbons (CFC‐12) concentration over a 40 year historical period. A long‐term simulation (one millennium), in which the current meteorological conditions have been kept statistically unchanged, has been used to determine the asymptotic dynamics. The results are consistent with previous measurements and estimates, suggesting that the model is suitable to qualitatively and quantitatively simulate deep water renewal in deep, temperate lakes, capturing the relative contribution and interaction of the different processes involved.
Seasonal and interannual variation in the cross‐equatorial meridional currents observed in the eastern Indian Ocean
Authors: Horii T. , Mizuno K. , Nagura M. , Miyama T. , Ando K.
Published: November 2013

Observations from moored subsurface acoustic Doppler current profilers (ADCPs) have revealed the structure of cross‐equatorial meridional currents in the eastern equatorial Indian Ocean. Using observational data longer than 8 years, we present observations of the seasonal and interannual variation in the cross‐equatorial currents in the 2000s. In line with earlier observations and numerical simulations, there were significant subsurface currents that displayed seasonal variation. The annual mean condition was dominated by currents during the boreal summer monsoon in which the Ekman transports are southward on both sides of the equator. The vertical structure of the mean meridional current displayed evidence of a shallow “equatorial roll,” consisting of northward surface flow and southward subsurface flow above the base of the isothermal mixed layer. The seasonal variation in upper 120 m meridional transport can be explained by wind‐driven cross‐equatorial Ekman/Sverdrup transport. Interannual variability was higher in the winter monsoon period than in the summer monsoon. The interannual variation could be related to the Pacific El Niño/Southern Oscillation (ENSO). ENSO‐induced variation in the southeasterly trade wind could modulate meridional Sverdrup transport. Implications of these observational results for meridional heat transport are discussed.
Oscillation modes of humidity over the Amazon basin derived from GPS RO profiles
Authors: Hierro R. , Llamedo P. , de la Torre A. , Alexander P.
Published: November 2013

The Global Positioning System radio occultation (GPS RO) technique provides vertical profiles of refractivity from which water vapor can be derived. It is possible to reproduce global, synoptic, and regional climatological patterns. From Formosa Satellite 3/Constellation Observing System for Meteorology Ionosphere and Climate mission data (2006–2013), the variability of the moistest region of Southern Hemisphere as the Amazon basin is analyzed. Applying different spatial and temporal filters, oscillation modes of the integrated specific humidity (Q) are found. A slight decreasing trend in Q is found during the studied period. Zonal variability of this variable averaged in time between Amazon basin latitudes presents a main mode of oscillation of a wavelength of one quarter of the Earth (T4). A secondary mode of wavelength at around T6 wavelength is also found after high‐pass filtering the original signal. In turn, temporal variability averaged over Amazon basin latitudes shows a wavelength at around 12 months, while secondary modes of 6 months are found.
Nonclinical Safety Assessment of Biologics, Including Vaccines
Authors: Hu Liangbiao George , Clarke David W.
Published: November 2013

To date the most common forms of biologics in development have been mAb, recombinant proteins, and vaccines. However, numerous new modalities are now being developed. One of these new modalities is bispecific antibodies, which are able to recognize two distinct targets at the same time and might bridge two targets together, which presents an opportunity for therapeutic gains (such as bringing cancer cells within closer proximity to cytotoxic T lymphocytes).When one considers species selection, if both complementarity‐determining regions (CDRs) do not have cross reactivity to the same species, one needs to understand how to appropriately assess the safety if the full pharmacological effect cannot be generated in one species. Therefore, these new biologic modalities offer great promise for the treatment of diseases but also challenges in developing the nonclinical toxicology testing paradigm to ensure the safety of the patients in the clinical trials.
Key Regulatory Guidelines for the Development of Biologics in the United States and Europe
Authors: Kingham Richard , Klasa Gabriela , Carver Krista Hessler
Published: November 2013

The United States and European Union have distinct but overlapping schemes for the regulation of biologics, ranging from the definition of a biologic itself to the technical requirements for approval.In the US, the definition of a biological product was developed over time, and historical context continues to inform its interpretation.In the EU, biologics are largely defined in terms of their active substances and methods of manufacture.Despite these differences, both jurisdictions recognize that biologics warrant special treatment, due to their distinct characteristics, such as their complex structures and susceptibility to variation during manufacturing.In the United States, Congress enacted a separate statute for biologics, whereas, in the EU, the general approval scheme plus certain specific requirements apply to biologics.Nevertheless, US and EU authorities have undertaken harmonization efforts with respect to some technical requirements for biologics applications, and thus, there is significant overlap in requirements imposed by both regions.This chapter provides an overview of the US and EU regulatory schemes, from nonclinical trials, through clinical trials, to approval.It then discusses considerations for global development of biologics, and it ends by discussing special issues for developing vaccines.
Chemical and Genetic Modification
Authors: Farys Monika , Ginn Claire L. , Badescu George O. , Peciak Karolina , Pawlisz Estera M. , Khalili Hanieh , Brocchini Steve J.
Published: November 2013

There are many natural post‐translational modifications of proteins (e.g., glycosylation, ubiquitination, acylation,and amino acid derivatization).Glycosylation is common for therapeutic proteins. Classes of proteins modified by glycosylation include monoclonal antibodies, blood factors, hematopoietic proteins, and cytokines. Excluding monoclonal antibodies, many proteins were, at least when they were first introduced to the clinic, designed to be used as a replacement protein for the corresponding endogenous protein. Maintaining control of the protein structure to be as close as possible to the structure of the endogeneous protein is therefore a key goal. In this review, we focus on (i) optimization of protein pharmacokinetics, (ii) improvement of protein properties to be used as medicines (this primarily includes reduction of immunogenic sequences and improvement of protein stability), (iii) addition of a therapeutic effect, and (iv) use of proteins as diagnostics.
Role and Application of Adjuvants and Delivery Systems in Vaccines
Authors: Gupta Rajesh K.
Published: November 2013

For more than 50 years, several novel adjuvants have been evaluated with human vaccines in preclinical and clinical studies. Before the past two decades, aluminum adjuvants were the only adjuvants used with routine administered human vaccines. During last 20 years, the licensure of a number of vaccines with alternate adjuvants has renewed optimism and enthusiasm in the development of novel adjuvants. And several mechanisms of action for aluminum based adjuvants have been proposed, which is discussed in this chapter. Nevertheless, the role of aluminum‐based adjuvants is still not clear.
Controlled‐Release Systems for Biologics
Authors: Oak Mayura , Mandke Rhishikesh , Layek Buddhadev , Sharma Gitanjali , Singh Jagdish
Published: November 2013

It is evident by the progress in new drug delivery technologies that much attention has been devoted toward the way in which biologics are delivered. As shown in this chapter, present efforts in the field of delivery of biologics have accelerated and widened the possibility of their use with therapeutic agents for treatment of various chronic disorders. From the times when achieving a zero‐order release profile was just an imaginary concept and controlled release technology was known only to a few scientists, it has now been established widely and has gained significant applications in variety of fields ranging from gene therapy to tissue engineering.