3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria

T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DR beta 1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of V beta 12 and V beta 6 TCR gene families in 67% of HLA-DR beta 1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DR beta 1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

Controlling regional monopolies in the natural gas industry: the role of transport capacity

This paper analyzes some optimal fiscal, pricing, and capacity investment policies for controlling regional monopoly power in the natural gas industry. By letting the set of control instruments available to the social planner vary, we provide a characterization of the technological and demand conditions under which “excess” capacity in the transport network arises in response to the loss of the two other control instruments, namely, transfers and pricing. Hence, the analysis yields some insights on an economy’s incentives to invest in infrastructures for the purpose of integrating geographically isolated markets.

Investment in transport capacity and regulation of regional monopolies in natural gas commodity markets

This paper develops a model of the regulator-regulated firm relationship in a regional natural gas commodity market which can be linked to a competitive market by a pipeline. We characterize normative policies under which the regulator, in addition to setting the level of the capacity of the pipeline, regulates the price of gas, under asymmetric information on the firm’s technology, and may (or may not) operate (two-way) transfers between consumers and the firm. We then focus on capacity and investigate how its level responds to the regulator’s taking account of the firm’s incentive compatibility constraints. The analysis yields some insights on the role that transport capacity investments may play as an instrument to improve the efficiency of geographically isolated markets.

Privatization in Colombia: a plant performance analysis

El artículo describe el programa de privatización en el sector real de la economía Colombiana durante los años noventa y ubica esta política en un contexto de desregulación de mercados y promoción de la inversión privada en la oferta de infraestructura publica y servicios públicos domiciliarios. El articulo evalúa el programa de privatización en los sectores manufacturero y de generación de energía eléctrica. Se hacen mediciones ex - post y análisis econométrico del desempeño de las firmas privatizadas. En el sector manufacturero la muestra analizada esta compuesta por 30 firmas manufactureras de gran tamaño, donde el Instituto de Fomento Industrial era socio fundador. Los principales resultados sugieren que estas firmas mantuvieron un comportamiento pro - cíclico relativo a su principal competidor privado y desestimaron planes drásticos de reestructuración operativa. Para el grupo de firmas de generación de energía el articulo estudia el impacto de la reforma regulatoria en el proceso de entrada al mercado, estructura de propiedad, competencia de mercado y eficiencia productiva. La medición de eficiencia productiva usa la técnica de Data Envelope Análisis para 33 plantas que representan el 85% de la capacidad instalada en la generación térmica de energía eléctrica. La muestra esta compuesta por plantas que estaban en funcionamiento antes de la reforma y las entrantes que comenzaron su operación comercial después de la reforma. Los resultados sugieren que los niveles de evidencia en la generación térmica a mejorado después de la reforma y que la política regulatoria ha tenido un efecto positivo en la eficiencia productiva.

The relationship between diffuse spectral reflectance of the soil and its cation exchange capacity is scale-dependent

Diffuse reflectance spectroscopy (DRS) is increasingly being used to predict numerous soil physical, chemical and biochemical properties. However, soil properties and processes vary at different scales and, as a result, relationships between soil properties often depend on scale. In this paper we report on how the relationship between one such property, cation exchange capacity (CEC), and the DRS of the soil depends on spatial scale. We show this by means of a nested analysis of covariance of soils sampled on a balanced nested design in a 16 km × 16 km area in eastern England. We used principal components analysis on the DRS to obtain a reduced number of variables while retaining key variation. The first principal component accounted for 99.8% of the total variance, the second for 0.14%. Nested analysis of the variation in the CEC and the two principal components showed that the substantial variance components are at the > 2000-m scale. This is probably the result of differences in soil composition due to parent material. We then developed a model to predict CEC from the DRS and used partial least squares (PLS) regression do to so. Leave-one-out cross-validation results suggested a reasonable predictive capability (R2 = 0.71 and RMSE = 0.048 molc kg− 1). However, the results from the independent validation were not as good, with R2 = 0.27, RMSE = 0.056 molc kg− 1 and an overall correlation of 0.52. This would indicate that DRS may not be useful for predictions of CEC. When we applied the analysis of covariance between predicted and observed we found significant scale-dependent correlations at scales of 50 and 500 m (0.82 and 0.73 respectively). DRS measurements can therefore be useful to predict CEC if predictions are required, for example, at the field scale (50 m). This study illustrates that the relationship between DRS and soil properties is scale-dependent and that this scale dependency has important consequences for prediction of soil properties from DRS data

Simulating current global river runoff with a global hydrological model: model revisions, validation, and sensitivity analysis

Global hydrological models (GHMs) model the land surface hydrologic dynamics of continental-scale river basins. Here we describe one such GHM, the Macro-scale - Probability-Distributed Moisture model.09 (Mac-PDM.09). The model has undergone a number of revisions since it was last applied in the hydrological literature. This paper serves to provide a detailed description of the latest version of the model. The main revisions include the following: (1) the ability for the model to be run for n repetitions, which provides more robust estimates of extreme hydrological behaviour, (2) the ability of the model to use a gridded field of coefficient of variation (CV) of daily rainfall for the stochastic disaggregation of monthly precipitation to daily precipitation, and (3) the model can now be forced with daily input climate data as well as monthly input climate data. We demonstrate the effects that each of these three revisions has on simulated runoff relative to before the revisions were applied. Importantly, we show that when Mac-PDM.09 is forced with monthly input data, it results in a negative runoff bias relative to when daily forcings are applied, for regions of the globe where the day-to-day variability in relative humidity is high. The runoff bias can be up to - 80% for a small selection of catchments but the absolute magnitude of the bias may be small. As such, we recommend future applications of Mac-PDM.09 that use monthly climate forcings acknowledge the bias as a limitation of the model. The performance of Mac-PDM.09 is evaluated by validating simulated runoff against observed runoff for 50 catchments. We also present a sensitivity analysis that demonstrates that simulated runoff is considerably more sensitive to method of PE calculation than to perturbations in soil moisture and field capacity parameters.

Temperature-responsive properties and drug solubilization capacity of amphiphilic copolymers based on N-vinylpyrrolidone and vinyl propyl ether

A series of amphiphilic copolymers were synthesized by free-radical copolymerization of N-vinylpyrrolidone (NVP) with vinyl propyl ether (VPE), and the structure of the copolymers was characterized by elemental analysis and gel permeation chromatography. The reactivity of VPE in copolymerization was found to be significantly lower than the reactivity of NVP, which resulted in a decrease of copolymers’ yields and molecular weights with higher content of VPE in the feed mixture. An investigation of the behavior of the copolymers in aqueous solutions at different temperatures by dynamic light scattering revealed the presence of lower critical solution temperature, which depending on the content of VPE ranged within 23−38 °C. Aqueous solutions of these copolymers were studied by fluorescent spectroscopy with pyrene as a polarity probe to reveal the formation of hydrophobic domains. The copolymers were found to be useful for enhancing the solubility of riboflavin in water.

Proteornics analysis unravels the functional repertoire of coronavirus nonstructural protein 3

Severe acute respiratory syndrome (SARS) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. Proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. A complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. Mass spectrometry and kinase profiling techniques identified nearly 200 incorporated host and viral proteins. We used published interaction data to identify hubs of connectivity with potential significance for virion formation. Surprisingly, the hub with the most potential connections was not the viral M protein but the nonstructurall protein 3 (nsp3), which is one of the novel virion components identified by mass spectrometry. Based on new experimental data and a bioinformatics analysis across the Coronaviridae, we propose a higher-resolution functional domain architecture for nsp3 that determines the interaction capacity of this protein. Using recombinant protein domains expressed in Escherichia coli, we identified two additional RNA-binding domains of nsp3. One of these domains is located within the previously described SARS-unique domain, and there is a nucleic acid chaperone-like domain located immediately downstream of the papain-like proteinase domain. We also identified a novel cysteine-coordinated metal ion-binding domain. Analyses of interdomain interactions and provisional functional annotation of the remaining, so-far-uncharacterized domains are presented. Overall, the ensemble of data surveyed here paint a more complete picture of nsp3 as a conserved component of the viral protein processing machinery, which is intimately associated with viral RNA in its role as a virion component.

From dichotic listening to the irrelevant sound effect: a behavioural and neuroimaging analysis of the processing of unattended speech

The assumption that ignoring irrelevant sound in a serial recall situation is identical to ignoring a non-target channel in dichotic listening is challenged. Dichotic listening is open to moderating effects of working memory capacity (Conway et al., 2001) whereas irrelevant sound effects (ISE) are not (Beaman, 2004). A right ear processing bias is apparent in dichotic listening, whereas the bias is to the left ear in the ISE (Hadlington et al., 2004). Positron emission tomography (PET) imaging data (Scott et al., 2004, submitted) show bilateral activation of the superior temporal gyrus (STG) in the presence of intelligible, but ignored, background speech and right hemisphere activation of the STG in the presence of unintelligible background speech. It is suggested that the right STG may be involved in the ISE and a particularly strong left ear effect might occur because of the contralateral connections in audition. It is further suggested that left STG activity is associated with dichotic listening effects and may be influenced by working memory span capacity. The relationship of this functional and neuroanatomical model to known neural correlates of working memory is considered.

A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.

Orthogonal on-off BPSK: a convenient signaling scheme for near-far resistant detection in DS/CDMA

This paper proposes a convenient signaling scheme-orthogonal on-off BPSK (O3BPSK)-for near-far (NF) resistant detection in asynchronous direct-sequence code-division multiple-access (DS/CDMA) systems (uplink). The temporally adjacent bits from different users in the received signals are decoupled by using the on-off signaling, and the original data rate is maintained with no increase in transmission rate by adopting an orthogonal structure. The detector at the receiver is a one-shot linear decorrelating detector, which depends upon neither hard decision nor specific channel coding. The application of O3 strategy to the differentially encoded BPSK (D-BPSK) sequences is also presented. Finally, some computer simulations are shown to confirm the theoretical analysis.

Subspace-based blind adaptive multiuser detection for multirate DS/CDMA signals

The existing dual-rate blind linear detectors, which operate at either the low-rate (LR) or the high-rate (HR) mode, are not strictly blind at the HR mode and lack theoretical analysis. This paper proposes the subspace-based LR and HR blind linear detectors, i.e., bad decorrelating detectors (BDD) and blind MMSE detectors (BMMSED), for synchronous DS/CDMA systems. To detect an LR data bit at the HR mode, an effective weighting strategy is proposed. The theoretical analyses on the performance of the proposed detectors are carried out. It has been proved that the bit-error-rate of the LR-BDD is superior to that of the HR-BDD and the near-far resistance of the LR blind linear detectors outperforms that of its HR counterparts. The extension to asynchronous systems is also described. Simulation results show that the adaptive dual-rate BMMSED outperform the corresponding non-blind dual-rate decorrelators proposed by Saquib, Yates and Mandayam (see Wireless Personal Communications, vol. 9, p.197-216, 1998).

A new signaling scheme for one-shot near-far resistant detection in DS/CDMA

This paper proposes a new signaling scheme: orthogonal on-off BPSK (O3BPSK), for near-far resistant detection in the asynchronous DS/CDMA systems (up-link). The temporally adjacent bits from different users in the received signals are decoupled by using the on-off signaling, and the original data rate is maintained with no increase in transmission rate by adopting an orthogonal structure. The detector at the receiver is a one-shot linear decorrelating detector, which depends upon neither hard-decision nor specific channel coding. Some computer simulations are shown to confirm the theoretical analysis.

A study of the antioxidant capacity of oak wood used in wine ageing and the correlation with polyphenol composition

The antioxidant capacity of oak wood used in the ageing of wine was studied by four different methods: measurement of scavenging capacity against a given radical (ABTS, DPPH), oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP). Although, the four methods tested gave comparable results for the antioxidant capacity measured in oak wood extracts, the ORAC method gave results with some differences from the other methods. Non-toasted oak wood samples displayed more antioxidant power than toasted ones due to differences in the polyphenol compositon. A correlation analysis revealed that ellagitannins were the compounds mainly responsible for the antioxidant capacity of oak wood. Some phenolic acids, mainly gallic acid, also showed a significant correlation with antioxidant capacity.

Mediterranean agriculture under climate change: adaptive capacity, adaptation, and ethics

In the coming decades, the Mediterranean region is expected to experience various climate impacts with negative consequences on agricultural systems and which will cause uneven reductions in agricultural production. By and large, the impacts of climate change on Mediterranean agriculture will be heavier for southern areas of the region. This unbalanced distribution of negative impacts underscores the significance and role of ethics in such a context of analysis. Consequently, the aim of this article is to justify and develop an ethical approach to agricultural adaptation in the Mediterranean and to derive the consequent implications for adaptation policy in the region. In particular, we define an index of adaptive capacity for the agricultural systems of the Mediterranean region on whose basis it is possible to group its different sub-regions, and we provide an overview of the suitable adaptation actions and policies for the sub-regions identified. We then vindicate and put forward an ethical approach to agricultural adaptation, highlighting the implications for the Mediterranean region and the limitations of such an ethical framework. Finally, we emphasize the broader potential of ethics for agricultural adaptation policy.