Clinical presentation, allergens, and management of wheat allergy

IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.

Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase

Superoxide-mediated clastogenesis is characteristic for various chronic inflammatory diseases with autoimmune reactions and probably plays a role in radiation-induced clastogenesis and in the congenital breakage syndromes. It is consistently prevented by exogenous superoxide dismutase (SOD), but not by heat-inactivated SOD, indicating that the anticlastogenic effect is related to the catalytic function of the enzyme. Increased superoxide production by activated monocytes/macrophages is followed by release of more long-lived metabolites, so-called clastogenic factors, which contain lipid peroxidation products, unusual nucleotides of inosine, and cytokines such as tumor necrosis factor α. Since these components are not only clastogenic, but can stimulate further superoxide production by monocytes and neutrophils, the genotoxic effects are self-sustaining. It is shown here that anticlastogenic effects of exogenous SOD are preserved despite extensive washing of the cells and removal of all extracellular SOD. Using flow cytometry and confocal laser microscopy, rapid adherence of the fluorescently labeled enzyme to the cell surface could be observed with slow uptake into the cell during the following hours. The degree of labeling was concentration and time dependent. It was most important for monocytes, compared with lymphocytes, neutrophils, and fibroblasts. The cytochrome c assay showed significantly diminished O2− production by monocytes, pretreated with SOD and washed thereafter. The preferential and rapid binding of SOD to monocytes may be of importance not only for the superoxide-mediated genotoxic effects, described above, but also from a therapeutic standpoint. It can explain the observation that beneficial effects of injected SOD lasted for weeks and months despite rapid clearance of the enzyme from the blood stream according to pharmacodynamic studies.

Hydrophobic sequence minimization of the α-lactalbumin molten globule

The molten globule, a widespread protein-folding intermediate, can attain a native-like backbone topology, even in the apparent absence of rigid side-chain packing. Nonetheless, mutagenesis studies suggest that molten globules are stabilized by some degree of side-chain packing among specific hydrophobic residues. Here we investigate the importance of hydrophobic side-chain diversity in determining the overall fold of the α-lactalbumin molten globule. We have replaced all of the hydrophobic amino acids in the sequence of the helical domain with a representative amino acid, leucine. Remarkably, the minimized molecule forms a molten globule that retains many structural features characteristic of a native α-lactalbumin fold. Thus, nonspecific hydrophobic interactions may be sufficient to determine the global fold of a protein.

Femtosecond dynamics of DNA-mediated electron transfer

Diverse biophysical and biochemical studies have sought to understand electron transfer (ET) in DNA in part because of its importance to DNA damage and its repair. However, the dynamics and mechanisms of the elementary processes of ET in this medium are not fully understood and have been heavily debated. Two fundamental issues are the distance over which charge is transported and the time-scale on which the transport through the π-stack of the DNA base pairs may occur. With femtosecond resolution, we report direct observation in DNA of ultrafast ET, initiated by excitation of tethered ethidium (E), the intercalated electron acceptor (A); the electron donor (D) is 7-deazaguanine (Z), a modified base, placed at different, fixed distances from A. The ultrafast ET between these reactants in DNA has been observed with time constants of 5 ps and 75 ps and was found to be essentially independent of the D–A separation (10–17 Å). However, the ET efficiency does depend on the D–A distance. The 5-ps decay corresponds to direct ET observed from 7-deazaguanine but not guanine to E. From measurements of orientation anisotropies, we conclude that the slower 75-ps process requires the reorientation of E before ET, similar to E/nucleotide complexes in water. These results reveal the nature of ultrafast ET and its mechanism: in DNA, ET cannot be described as in proteins simply by a phenomenological parameter, β. Instead, the involvement of the base pairs controls the time scale and the degree of coherent transport.

Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing human LCAT had 15-fold greater plasma LCAT activity that nontransgenic control rabbits. This degree of overexpression was associated with a 6.7-fold increase in the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3% cholesterol diet, the HDL cholesterol concentrations increased from 24 +/- 1 to 39 +/- 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased from 161 +/- 5 to 200 +/- 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n = 9). Although the baseline non-HDL concentrations of control (4 +/- 3 mg/dl) and transgenic rabbits (18 +/- 4 mg/dl) were similar, the cholesterol-rich diet raised the non-HDL cholesterol concentrations, reflecting the atherogenic very low density, intermediate density, and low density lipoprotein particles observed by gel filtration chromatography. The non-HDL cholesterol rose to 509 +/- 57 mg/dl in controls compared with only 196 +/- 14 mg/dl in the LCAT transgenic rabbits (P < 0.005). The differences in the plasma lipoprotein response to a cholesterol-rich diet observed in the transgenic rabbits paralleled the susceptibility to developing aortic atherosclerosis. Compared with nontransgenic controls, LCAT transgenic rabbits were protected from diet-induced atherosclerosis with significant reductions determined by both quantitative planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P < 0.009). Our results establish the importance of LCAT in the metabolism of both HDL and apolipoprotein B-containing lipoprotein particles with cholesterol feeding and the response to diet-induced atherosclerosis. In addition, these findings identify LCAT as a new target for therapy to prevent atherosclerosis.

Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.

Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture.

The N-terminal region (A/B) of rat thyroid hormone receptors alpha 1, beta 1, but not beta 2 contains a strong thyroid hormone-dependent transactivation function.

In this study we have investigated the role of the N-terminal region of thyroid hormone receptors (TRs) in thyroid hormone (TH)-dependent transactivation of a thymidine kinase promoter containing TH response elements composed either of a direct repeat or an inverted palindrome. Comparison of rat TR beta 1 with TR beta 2 provides an excellent model since they share identical sequences except for their N termini. Our results show that TR beta 2 is an inefficient TH-dependent transcriptional activator. The degree of transactivation corresponds to that observed for the mutant TR delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2. Thus, TH-dependent activation appears to be associated with two separate domains. The more important region, however, is embedded in the N-terminal domain. Furthermore, the transactivating property of TR alpha 1 was also localized to the N-terminal domain between amino acids 19 and 30. Using a coimmunoprecipitation assay, we show that the differential interaction of the N terminus of TR beta 1 and TR beta 2 with transcription factor IIB correlates with the TR beta 1 activation function. Hence, our results underscore the importance of the N-terminal region of TRs in TH-dependent transactivation and suggest that a transactivating signal is transmitted to the general transcriptional machinery via a direct interaction of the receptor N-terminal region with transcription factor IIB.

Avaliação de eficiência das cooperativas de crédito no Brasil: um estudo com base na intermediação financeira e na prestação de serviços

As cooperativas de crédito são instituições financeiras que têm como finalidade principal a prestação de serviços bancários e de intermediação financeira voltando-se para a geração de benefícios ao cooperado, através de benefícios econômicos encontrados sob a forma cooperativada. Considerando o objetivo destas organizações, o presente trabalho teve por objetivo avaliar a eficiência das mesmas considerando duas vertentes: 1) a atividade de intermediação financeira; e 2) a atividade de prestação de serviços bancários, a partir de variáveis contábeis. A técnica utilizada para a avaliação da eficiência foi a Análise Envoltória de Dados e foram analisados os determinantes da eficiência por meio de regressões do tipo Tobit. A amostra é composta por 315 cooperativas singulares listadas na base de dados do Banco Central do Brasil e foram utilizados os dados dos balancetes anuais e semestrais (soma dos semestres para as contas de resultado de cada ano) apresentados para período de 2007 a 2014. Os resultados indicaram baixa eficiência das cooperativas na prestação de serviços bancários, com 73% da amostra apresentando ineficiência ao longo de todos os anos do período em análise. Na atividade de intermediação financeira 20 cooperativas foram eficientes ao longo do período completo, com as demais apresentando graus de ineficiência abaixo de 16% em todos os anos. Quanto aos determinantes da eficiência, verificou-se como principais fatores na atividade de intermediação financeira a Imobilização, a Insolvência, o Descasamento Passivo e as Despesas Administrativas, enquanto na atividade de prestação de serviços os principais determinantes foram a Captação por Floating e as Despesas Administrativas. Os resultados da eficiência na intermediação financeira indicaram baixos graus de ineficiência, enquanto os altos graus de ineficiência na prestação de serviços bancários alertaram para a pouca importância dada ao fornecimentos destes serviços e para a importância de se utilizar dois modelos distintos para a avaliação da eficiência em cooperativas de crédito, dado o comportamento desvinculado entre as duas atividades avaliadas.

Avoiding Extinction: An Evaluation of Short-Term Recovery Recommendations for the Endangered Rio Grande Silvery Minnow

The endangered Rio Grande silvery minnow (Hybognathus amarus; RGSM) is nearing extinction and requires immediate recovery actions. In a draft report to the Middle Rio Grande Program, a Program Advisory Panel (PAP) recommended 34 short-term recovery measures to be implemented within the next five years, and 21 long-term recovery actions. However, these recommendations need further analysis to determine if and how the actions could be implemented. This project evaluated short-term recommendations provided by the PAP to identify the most effective and rank the relative importance of the actions. These recommendations were divided into 7 recovery categories: population augmentation (5 recommendations); hydrologic regimen (4 recommendations); physical habitat (3 recommendations); biological component of habitat (2 recommendations); population monitoring (6 recommendations); monitoring, analysis, and modeling (12 recommendations); and information and planning (2 recommendations). Each recommendation was evaluated for its potential to produce anticipated recovery progress for the RGSM based on assessments of the degree of feasibility, cost effectiveness, and associated potential consequences if fully implemented. In addition, other alternatives in a range of options were also considered where applicable. In each case, recommendations were evaluated from on-site visits, interviews with researchers and resource managers, and literature review. Based on the research findings, three major groupings of the recovery categories were identified: natural aspects of recovery, program aspects of recovery, and emergency measures. At least one recovery category within each major grouping was considered important by the respondents, which indicates that each grouping is of high importance in relation to the situation at hand. However, actions within each grouping have varying priorities given constraints on available resources, time, and budget. An integrated approach that accounts for the complexity of the river system and the species itself was considered the best approach to avoid extinction while ensuring long-term sustainability. Results of these analyses were provided directly to the PAP for their review, and it is anticipated that project results could advance implementation of the most appropriate immediate recovery actions needed to prevent extinction of the RGSM.

La biodiversidad marina en la Región de Murcia

Actualmente se ha detectado la existencia de un gradiente de biodiversidad, marcado por el eje Nor-Oeste/Sur-Este y justificado por variables ambientales claves como la latitud, salinidad, temperatura, circulación de las masas de agua, etc. La conjunción de estas variables hacen del litoral de Murcia una de las zonas de mayor biodiversidad del Mediterráneo, mar ya de por sí caracterizado por una alta biodiversidad. Una de las singularidades paisajísticas del litoral murciano son los cañones submarinos cercanos a la línea de costa, propuestos en la Cumbre Mundial de Desarrollo Sostenible de Johannesburgo (2002) como hábitats únicos de gran importancia ecológica. La disposición geográfica del litoral murciano lo convierte en una pantalla que frena el agua procedente del Atlántico y que pasa por Gibraltar, configurando un espacio marino en el que convergen especies mediterráneas y atlánticas, tanto a nivel pelágico como nerítico. La Región de Murcia muestra una gran cantidad de hábitats marinos contenidos en la Lista Patrón de Hábitats Marinos presentes en España, pero si existe un hábitat emblemático en el medio marino mediterráneo y, por ende, en el litoral de la Región de Murcia, es el generado por las praderas de Posidonia oceanica (Posidonietum oceanicae). Otro importantísimo valor natural regional es la laguna salada del Mar Menor, hábitat prioritario de la Directiva Hábitats, que alberga importantes poblaciones de caballito de mar, langostinos y otras especies de interés, además de ser un importante lugar de paso e invernada de aves acuáticas, limícolas y marinas.

Workshops in “Construction of Structures I”: A new teaching methodology in the Building Engineering Degree

Both the current economic situation in the construction sector and the continuous normative changes in the building area imply the use of new methodologies to enhance students’ competences in the degree of Building Engineer. The aim of this paper is to present, analyse and discuss the development of constructive workshops as a new teaching methodology used in the subject of Construction of Structures I at the University of Alicante to complement the constructive and technical knowledge acquired by our students and to enhance their communicative and representation skills essential for their professional practice in the future. The used methodology is based on the development of three-dimensional construction details (in groups of 3 or 4 students) to be shown in two A1-pannels exposed in the corridors of the Polytechnic School. Thus, students’ work approaches constructive problems in a global way by discussing simultaneously with teachers and other groups about the most suitable solution on each case. This contribution has multiperspective results and improves criticism of students in different areas, encouraging new learning strategies and active participation. What is more, on-line information and web applications have been used to prepare and organize this kind of workshops, allowing students to use new technologies as a complementary learning methodology. In conclusion, the use of these new workshops in the Degree of Building Engineer stimulates an interactive class versus a traditional lecture where the participative groups´ attitude and the development of oral presentations dissolve the traditional boundaries regarding public communication skills of the students in the Degree.

Building from building waste: The development of an instrument to determine the circularity of materials from the existing building stock in order to maximise high quality reuse

On a global level the population growth and increase of the middle class lead to a growing demand on material resources. The built environment has an enormous impact on this scarcity. In addition, a surplus of construction and demolition waste is a common problem. The construction industry claims to recycle 95% of this waste but this is in fact mainly downcycling. Towards the circular economy, the quality of reuse becomes of increasing importance. Buildings are material warehouses that can contribute to this high quality reuse. However, several aspects to achieve this are unknown and a need for more insight into the potential for high quality reuse of building materials exists. Therefore an instrument has been developed that determines the circularity of construction waste in order to maximise high quality reuse. The instrument is based on three principles: ‘product and material flows in the end of life phase’, ‘future value of secondary materials and products’ and ‘the success of repetition in a new life cycle’. These principles are further divided into a number of criteria to which values and weighting factors are assigned. A degree of circularity can then be determined as a percentage. A case study for a typical 70s building is carried out. For concrete, the circularity is increased from 25% to 50% by mapping out the potential for high quality reuse. During the development of the instrument it was clarified that some criteria are difficult to measure. Accurate and reliable data are limited and assumptions had to be made. To increase the reliability of the instrument, experts have reviewed the instrument several times. In the long-term, the instrument can be used as a tool for quantitative research to reduce the amount of construction and demolition waste and contribute to the reduction of raw material scarcity.

European Criminal Law and General Principles of Union Law. Research Papers in Law, 5/2005

From the Introduction. The European Court of Justice, partly followed in this by the European legislator, has regulated Community law and policy through a set of general principles of law. For the Community legal order in the first pillar, general legal principles have developed from functional policy areas such as the internal market, the customs union, the monetary union, the common agricultural policy, the European competition policy, etc., which are of great importance for the quality and legitimacy of Community law. The principles in question are not so much general legal principles of an institutional character, such as the priority of Community law, direct effect or Community loyalty, but rather principles of law which shape the fundamental rights and basic rights of the citizen. I refer to the principle of legality, of nulla poena, the inviolability of the home, the nemo tenetur principle, due process, the rights of the defence, etc. Many of these legal principles have been elevated to primary Community law status by the European Court of Justice, often as a result of preliminary questions. Nevertheless, a considerable number of them have also been elaborated in the context of contentious proceedings before the Court of Justice, such as in the framework of European competition law and European public servants law.

An Analysis of the Capitalisation of CAP Payments into Land Rental Rates in Ireland. Factor Markets Working Document No. 68, August 2013

EDITED VERSION SOON TO BE PUBLISHED In this paper the effect of decoupling on the capitalisation of agricultural subsidies into agricultural rents in Ireland are analysed using a dynamic rental equations estimated with a two step system GMM estimator that accounts for expectation error and endogenous regressors. The findings illustrate the importance of institutional details in determining the extent to which subsidies are capitalised. In the period prior to decoupling Pillar 1 subsidies were highly capitalised into Irish agricultural rents in both the short and the long run. Depending on the farm system considered between 58 to 80 cents per euro of subsidies were capitalised into agricultural rents. In the post decoupling period the rate at which Pillar 1 subsidies are capitalised into Irish agricultural rents is found to have declined. This change is likely due to short term character of the Irish agricultural land rental market, where 11 month rental periods predominate, and the freedom that the 2003 reform of the CAP offered farmers to consolidate entitlements established on rented land. The generally very short term nature of Irish agricultural rental contracts offered farmers an opportunity to consolidate entitlements that is unlikely to have arisen in other Member States with agricultural land rental markets characterised by long term contracts. The results in both the pre and post decoupling periods highlight the high degree of inertia of agricultural rents in Ireland, and the importance of accounting for dynamics when investigating the capitalisation of agricultural subsidies into land rents. The high degree of inertia in rents means that the impact of previously capitalised agricultural policy persists through time.

Mesure de la performance dans les organisations de réadaptation en déficience physique

La présente thèse vise à évaluer le degré d’implantation et d’utilisation de systèmes de mesure de la performance (SMP) par les décideurs des organisations de réadaptation et à comprendre les facteurs contextuels ayant influencé leur implantation. Pour ce faire, une étude de cas multiples a été réalisée comprenant deux sources de données: des entrevues individuelles avec des cadres supérieurs des organisations de réadaptation du Québec et des documents organisationnels. Le cadre conceptuel Consolidated Framework for Implementation Research a été utilisé pour guider la collecte et l’analyse des données. Une analyse intra-cas ainsi qu’une analyse inter-cas ont été réalisées. Nos résultats montrent que le niveau de préparation organisationnelle à l’implantation d’un SMP était élevé et que les SMP ont été implantés avec succès et utilisés de plusieurs façons. Les organisations les ont utilisés de façon passive (comme outil d’information), de façon ciblée (pour tenter d’améliorer des domaines sous-performants) et de façon politique (comme outil de négociation auprès des autorités gouvernementales). Cette utilisation diversifiée des SMP est suscitée par l’interaction complexe de facteurs provenant du contexte interne propre à chaque organisation, des caractéristiques du SMP, du processus d’implantation appliqué et du contexte externe dans lequel évoluent ces organisations. Au niveau du contexte interne, l’engagement continu et le leadership de la haute direction ont été décisifs dans l’implantation du SMP de par leur influence sur l’identification du besoin d’un SMP, l’engagement des utilisateurs visés dans le projet, la priorité organisationnelle accordée au SMP ainsi que les ressources octroyées à son implantation, la qualité des communications et le climat d’apprentissage organisationnel. Toutefois, même si certains de ces facteurs, comme les ressources octroyées à l’implantation, la priorité organisationnelle du SMP et le climat d’apprentissage se sont révélés être des barrières à l’implantation, ultimement, ces barrières n’étaient pas suffisamment importantes pour entraver l’utilisation du SMP. Cette étude a également confirmé l’importance des caractéristiques du SMP, particulièrement la perception de qualité et d’utilité de l’information. Cependant, à elles seules, ces caractéristiques sont insuffisantes pour assurer le succès d’implantation. Cette analyse d’implantation a également révélé que, même si le processus d’implantation ne suit pas des étapes formelles, un plan de développement du SMP, la participation et l’engagement des décideurs ainsi que la désignation d’un responsable de projet ont tous facilité son implantation. Cependant, l’absence d’évaluation et de réflexion collective sur le processus d’implantation a limité le potentiel d’apprentissage organisationnel, un prérequis à l’amélioration de la performance. Quant au contexte externe, le soutien d’un organisme externe s’est avéré un facilitateur indispensable pour favoriser l’implantation de SMP par les organisations de réadaptation malgré l’absence de politiques et incitatifs gouvernementaux à cet effet. Cette étude contribue à accroître les connaissances sur les facteurs contextuels ainsi que sur leurs interactions dans l’utilisation d’innovations tels les SMP et confirme l’importance d’aborder l’analyse de l’implantation avec une perspective systémique.