Dissecting TCR-MHC/peptide complex interactions with A2/peptide multimers incorporating tumor antigen peptide variants: crucial role of interaction kinetics on functional outcomes.

Soluble peptide/MHC-class-I (pMHC) multimers have recently emerged as unique reagents for the study of specific interactions between the pMHC complex and the TCR. Here, we assessed the relative binding efficiency of a panel of multimers incorporating single-alanine-substituted variants of the tumor-antigen-derived peptide MAGE-A10(254-262) to specific CTL clones displaying different functional avidity. For each individual clone, the efficiency of binding of multimers incorporating MAGE-A10 peptide variants was, in most cases, in good although not linear correlation with the avidity of recognition of the corresponding variant. In addition, we observed two types of discrepancies between efficiency of recognition and multimer binding. First, for some peptide variants, efficient multimer binding was detected in the absence of measurable effector functions. Some of these peptide variants displayed antagonist activity. Second, when comparing different clones we found clear discrepancies between the dose of peptide required to obtain half-maximal lysis in CTL assays and the binding efficiency of the corresponding multimers. These discrepancies, however, were resolved when the differential stability of the TCR/pMHC complexes was determined. For individual clones, decreased recognition correlated with increased TCR/pMHC off-rate. TCR/pMHC complexes formed by antagonist ligands displayed off-rates faster than those of TCR/pMHC complexes formed with weak agonists. In addition, when comparing different clones, the efficiency of multimer staining correlated better with relative multimer off-rates than with half-maximal lysis values. Altogether, the data presented here reconcile and extend our previous results on the impact of the kinetics of interaction of TCR with pMHC complexes on multimer binding and underline the crucial role of TCR/pMHC off-rates for the functional outcome of such interactions.

Multicast algorithms evaluation using an adaptative routing in ATM networks

This paper proposes a multicast implementation based on adaptive routing with anticipated calculation. Three different cost measures for a point-to-multipoint connection: bandwidth cost, connection establishment cost and switching cost can be considered. The application of the method based on pre-evaluated routing tables makes possible the reduction of bandwidth cost and connection establishment cost individually

Remediation of a marine shore tailings deposit and the importance of water-rock interaction on element cycling in the coastal aquifer

We present the study of the geochemical processes associated with the first successful remediation of a marine shore tailings deposit in a coastal desert environment (Bahia de Ite, in the Atacama Desert of Peru). The remediation approach implemented a wetland on top of the oxidized tailings. The site is characterized by a high hydrauliz gradient produced by agricultural irrigation on upstream gravel terraces that pushed river water (similar to 500 mg/L SO(4)) toward the sea and through the tailings deposit. The geochemical and isotopic (delta(2)H(water) and delta(18)O(water), delta(34)S(sulfate) , delta(18)O(sulfate)) approach applied here revealed that evaporite horizons (anhydrite and halite) in the gravel terraces are the source of increased concentrations of SO(4), Cl, and Na up to similar to 1500 mg/L in the springs at the base of the gravel terraces. Deeper groundwater interacting with underlying marine sequences increased the concentrations of SO(4), Cl, and Na up to 6000 mg/L and increased the alkalinity up to 923 mg/L CaCO(3) eq. in the coastal aquifer. These waters infiltrated into the tailings deposit at the shelf-tailings interface. Nonremediated tailings had a low-pH oxidation zone (pH 1-4) with significant accumulations of efflorescent salts (10-20 cm thick) at the surface because of upward capillary transport of metal cations in the arid climate. Remediated tailings were characterized by neutral pH and reducing conditions (pH similar to 7, Eh similar to 100 mV). As a result, most bivalent metals such as Cu, Zn, and Ni had very low concentrations (around 0.01 mg/L or below detection limit) because of reduction and sorption processes. In contrast, these reducing conditions increased the mobility of iron from two sources in this system: (1) The originally Fe(III)-rich oxidation zone, where Fe(II) was reduced during the remediation process and formed an Fe(II) plume, and (2) reductive dissolution of Fe(III) oxides present in the original shelf lithology formed an Fe-Mn plume at 10-m depth. These two Fe-rich plumes were pushed toward the shoreline where more oxidizing and higher pH conditions triggered the precipitation of Fe(HI)hydroxide coatings on silicates. These coatings acted as a filter for the arsenic, which naturally infiltrated with the river water (similar to 500 mu g/L As natural background) into the tailings deposit.

Disentangling the attention network test: behavioral, event related potentials, and neural source analyses.

BACKGROUND The study of the attentional system remains a challenge for current neuroscience. The "Attention Network Test" (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. RESULTS This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. CONCLUSIONS The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects.

Metabolomic insights into the intricate gut microbial-host interaction in the development of obesity and type 2 diabetes.

Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial-host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial-host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders.

Networks in Argentine agriculture: a multiple-case study approach

Argentina is among the four largest producers of soybeans, sunflower, corn, and wheat, among other agricultural products. Institutional and policy changes during the 1990s fostered the development of Argentine agriculture and the introduction of innovative process and product technologies (no-till, agrochemicals, GMO, GPS) and new investments in modern, large-scale sunflower and soybean processing plants. In addition to technological changes, a "quiet revolution" occurred in the way agricultural production was carried out and organized: from self-production or ownership agriculture to a contract-based agriculture. The objective of this paper is to explore and describe the emergence of networks in the Argentine crop production sector. The paper presents and describes four cases that currently represent about 50% of total grain and oilseed production in Argentina: "informal hybrid form", "agricultural trust fund", "investor-oriented corporate structure", and "network of networks". In all cases, hybrid forms involve a group of actors linked by common objectives, mainly to gain scale, share resources, and improve the profitability of the business. Informal contracts seem to be the most common way of organizing the agriculture process, but using short-term contracts and sequential interfirm collaboration. Networks of networks involve long-term relationships and social development, and reciprocal interfirm collaboration. Agricultural trust fund and investor-oriented corporate structures have combined interfirm collaboration and medium-term relationships. These organizational forms are highly flexible and show a great capacity to adapt to challenges; they are competitive because they enjoy aligned incentives, flexibility, and adaptability.

Resource management research in Passive Optical Networks (PON)

Next Generation Access Networks (NGAN) are the new step forward to deliver broadband services and to facilitate the integration of different technologies. It is plausible to assume that, from a technological standpoint, the Future Internet will be composed of long-range high-speed optical networks; a number of wireless networks at the edge; and, in between, several access technologies, among which, the Passive Optical Networks (xPON) are very likely to succeed, due to their simplicity, low-cost, and increased bandwidth. Among the different PON technologies, the Ethernet-PON (EPON) is the most promising alternative to satisfy operator and user needs, due to its cost, flexibility and interoperability with other technologies. One of the most interesting challenges in such technologies relates to the scheduling and allocation of resources in the upstream (shared) channel. The aim of this research project is to study and evaluate current contributions and propose new efficient solutions to address the resource allocation issues in Next Generation EPON (NG-EPON). Key issues in this context are future end-user needs, integrated quality of service (QoS) support and optimized service provisioning for real time and elastic flows. This project will unveil research opportunities, issue recommendations and propose novel mechanisms associated with the convergence within heterogeneous access networks and will thus serve as a basis for long-term research projects in this direction. The project has served as a platform for the generation of new concepts and solutions that were published in national and international conferences, scientific journals and also in book chapter. We expect some more research publications in addition to the ones mentioned to be generated in a few months.

Análisis de contenidos de páginas web sobre servicios de control de plagas en salud pública

Introduction: Our goal was to know the web contents and examine the technical information pest control services available to users through their webpages. Method: A total of 70 webpages from biocides services in the province of Málaga (Spain) were analyzed. We used 15 evaluation indicators grouped into 5 parameters relating to data of the service provider; information’s reliability and services; accuracy of content and writing style; technical resources and interaction with the users. As test instruments were used sectoral legislation, official records of products and deliveries, standards and technical guides. Results: Companies showed a remarkable degree of awareness with the implementation and use of new technologies. Aspects negative that they can have an impact on the confidence of users, relating to the reliability of the information and deficiencies associated with the description of the services portfolio and credentials of the companies were identified. The integration and use of collaborative platforms 2.0 was poorly developed and squandered. Discussion: It is possible to improve the trust of users intervening in those aspects that affect the reliability of the information provided on the web.

Drivers of human resource management competences development in Brazilian multinational subsidiaries: a multilevel research

This article aims to verify the factors associated with the development of human resource management (HRM) competences in foreign subsidiaries of Brazilian multinationals. These competences are essential in that they allow foreign units to adopt HRM practices that are consistent with the countries or markets in which they operate. A multilevel research was conducted, involving headquarters and subsidiaries of major Brazilian companies; the empirical analysis employed hierarchical linear modelling. Despite the recurrent debate on global standardisation versus local adaptation, it was identified that the integration of international HRM policies (addressing simultaneously global guidelines and local response) may stimulate competences development. In addition, interaction in external networks in the host country may enhance the development of HRM competences in the subsidiaries. However, specific cultural factors of the company may inhibit development activity in units abroad.

Identification of key amino acids of the mouse mammary tumor virus superantigen involved in the specific interaction with T-cell receptor V(beta) domains.

Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class II by the variable region of the beta chain (V(beta)) of the T-cell receptor. The C-terminal 30 to 40 amino acids of the superantigen of different MMTVs display high sequence variability that correlates with the recognition of particular T-cell receptor V(beta) chains. Interestingly, MMTV(SIM) and mtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor V(beta) specificities. To determine the importance of these few differences for specific V(beta) interaction, we studied superantigen responses in mice to chimeric and mutant MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We show that only a few changes (two to six residues) within the C terminus are necessary to modify superantigen recognition by specific V(beta)s. Thus, the introduction of the MMTV(SIM) residues 314-315 into the mtv-8 superantigen greatly decreased its V(beta)12 reactivity without gain of MMTV(SIM)-specific function. The introduction of MMTV(SIM)-specific residues 289 to 295, however, induced a recognition pattern that was a mixture of MMTV(SIM)- and mtv-8-specific V(beta) reactivities: both weak MMTV(SIM)-specific V(beta)4 and full mtv-8-specific V(beta)11 recognition were observed while V(beta)12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8 superantigen established normal MMTV(SIM)-specific V(beta)4 reactivity and completely abolished mtv-8-specific V(beta)5, -11, and -12 interactions. These new functional superantigens with mixed V(beta) recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor V(beta) domain within the 30 C-terminal residues of the viral superantigen.

Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Uncorrelatedness in growing networks with preferential survival of nodes

The emergence of uncorrelated growing networks is proved when nodes are removed either uniformly or under the preferential survival rule recently observed in the World Wide Web evolution. To this aim, the rate equation for the joint probability of degrees is derived, and stationary symmetrical solutions are obtained, by passing to the continuum limit. When a uniformly random removal of extant nodes and linear preferential attachment of new nodes are at work, we prove that the only stationary solution corresponds to uncorrelated networks for any removal rate r ∈ (0,1). In the more general case of preferential survival of nodes, uncorrelated solutions are also obtained. These results generalize the uncorrelatedness displayed by the (undirected) Barab´asi-Albert network model to models with uniformly random and selective (against low degrees) removal of nodes

A simulation-based algorithm for solving the resource-assignment problem in satellite telecommunication networks

This paper proposes an heuristic for the scheduling of capacity requests and the periodic assignment of radio resources in geostationary (GEO) satellite networks with star topology, using the Demand Assigned Multiple Access (DAMA) protocol in the link layer, and Multi-Frequency Time Division Multiple Access (MF-TDMA) and Adaptive Coding and Modulation (ACM) in the physical layer.

Comparison of early cortical networks in efficient and inefficient visual search: an event-related potential study.

Functional magnetic resonance imaging studies have indicated that efficient feature search (FS) and inefficient conjunction search (CS) activate partially distinct frontoparietal cortical networks. However, it remains a matter of debate whether the differences in these networks reflect differences in the early processing during FS and CS. In addition, the relationship between the differences in the networks and spatial shifts of attention also remains unknown. We examined these issues by applying a spatio-temporal analysis method to high-resolution visual event-related potentials (ERPs) and investigated how spatio-temporal activation patterns differ for FS and CS tasks. Within the first 450 msec after stimulus onset, scalp potential distributions (ERP maps) revealed 7 different electric field configurations for each search task. Configuration changes occurred simultaneously in the two tasks, suggesting that contributing processes were not significantly delayed in one task compared to the other. Despite this high spatial and temporal correlation, two ERP maps (120-190 and 250-300 msec) differed between the FS and CS. Lateralized distributions were observed only in the ERP map at 250-300 msec for the FS. This distribution corresponds to that previously described as the N2pc component (a negativity in the time range of the N2 complex over posterior electrodes of the hemisphere contralateral to the target hemifield), which has been associated with the focusing of attention onto potential target items in the search display. Thus, our results indicate that the cortical networks involved in feature and conjunction searching partially differ as early as 120 msec after stimulus onset and that the differences between the networks employed during the early stages of FS and CS are not necessarily caused by spatial attention shifts.