Comparative analysis of the corps en cerise in several species of Laurencia (Ceramiales, Rhodophyta) from the Atlantic Ocean

Different species of Laurencia have proven to be a rich source of natural products yielding interesting bioactive halogenated secondary metabolites, such as terpenoids and acetogenins. It is shown that such compounds are accumulated in the spherical, reniform to claviform refractive inclusions called corps en cerise (CC), which are intensively osmiophilic and located mainly in the cortical cells of the thalli and also in trichoblast cells. Up to now, it was believed that CC were present only in these two kinds of cells. Recently, however, a species of Laurencia, L. marilzae, with CC in all cells of the thallus, i.e., cortical, medullary, including the pericentral and axial cells, as well as in the trichoblasts, was described from the Canary Islands, and subsequently also reported to Brazil and Mexico. Within the Laurencia complex, only Laurencia species produce CC. Since the species of Laurencia are targets of interest for the prospection of bioactive substances due to their potential antibacterial, antifungal, anticholinesterasic, antileishmanial, cytotoxic, and antioxidant activities, the present paper carries out a comparative analysis of the corps en cerise in several species of Laurencia from the Atlantic Ocean to obtain basic information that can support natural product bioprospection projects. Our results show that the number and size of the CC are constant within a species, independent of the geographical distribution, corroborating their use for taxonomical purposes to differentiate groups of species that present a lower number from those that have a higher number. In this regard, there was a tendency for the number of CC to be higher in some species of Laurencia from the Canary Islands. The presence of CC can also be used to distinguish species in which these organelles are present in all cells of the thallus from those in which CC are restricted to the cortical cells. Among the species analyzed, L. viridis displayed the most varied secondary metabolites composition, such as sesquiterpenes, diterpenes, triterpenes, all of which showed potent antiviral, cytotoxic, and antitumoral activities, including protein phosphatase type 2A (PP2A) inhibitory effects.

Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis

BACKGROUND: The retention of patients in antiretroviral therapy (ART) programmes is an important issue in resource-limited settings. Loss to follow up can be substantial, but it is unclear what the outcomes are in patients who are lost to programmes. METHODS AND FINDINGS: We searched the PubMed, EMBASE, Latin American and Caribbean Health Sciences Literature (LILACS), Indian Medlars Centre (IndMed) and African Index Medicus (AIM) databases and the abstracts of three conferences for studies that traced patients lost to follow up to ascertain their vital status. Main outcomes were the proportion of patients traced, the proportion found to be alive and the proportion that had died. Where available, we also examined the reasons why some patients could not be traced, why patients found to be alive did not return to the clinic, and the causes of death. We combined mortality data from several studies using random-effects meta-analysis. Seventeen studies were eligible. All were from sub-Saharan Africa, except one study from India, and none were conducted in children. A total of 6420 patients (range 44 to 1343 patients) were included. Patients were traced using telephone calls, home visits and through social networks. Overall the vital status of 4021 patients could be ascertained (63%, range across studies: 45% to 86%); 1602 patients had died. The combined mortality was 40% (95% confidence interval 33%-48%), with substantial heterogeneity between studies (P<0.0001). Mortality in African programmes ranged from 12% to 87% of patients lost to follow-up. Mortality was inversely associated with the rate of loss to follow up in the programme: it declined from around 60% to 20% as the percentage of patients lost to the programme increased from 5% to 50%. Among patients not found, telephone numbers and addresses were frequently incorrect or missing. Common reasons for not returning to the clinic were transfer to another programme, financial problems and improving or deteriorating health. Causes of death were available for 47 deaths: 29 (62%) died of an AIDS defining illness. CONCLUSIONS: In ART programmes in resource-limited settings a substantial minority of adults lost to follow up cannot be traced, and among those traced 20% to 60% had died. Our findings have implications both for patient care and the monitoring and evaluation of programmes.

Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: relevance to capillary occlusion in diabetic retinopathy

The exact mechanism for capillary occlusion in diabetic retinopathy is still unclear, but increased leukocyte-endothelial cell adhesion has been implicated. We examined the possibility that posttranslational modification of surface O-glycans by increased activity of core 2 transferase (UDP-Glc:Galbeta1-3GalNAcalphaRbeta-N-acetylglucoaminyltr ansferase) is responsible for increased adhesion of leukocytes to vascular endothelium in diabetes. The mean activity of core 2 transferase in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients was higher compared with age-matched control subjects (1,638 +/- 91 [n = 42] vs. 249 +/- 35 pmol x h(-1) x mg(-1) protein [n = 24], P = 0.00013; 1,459 +/- 194 [n = 58] vs. 334 +/- 86 [n = 11], P = 0.01). As a group, diabetic patients with retinopathy had significantly higher mean activity of core 2 transferase compared with individuals with no retinopathy. There was a significant association between enzyme activity and severity of retinopathy in type 1 and type 2 diabetic patients. There was a strong correlation between activity of core 2 transferase and extent of leukocyte adhesion to cultured retinal capillary endothelial cells for diabetic patients but not for age-matched control subjects. Results from transfection experiments using human myelocytic cell line (U937) demonstrated a direct relationship between increased activity of core 2 transferase and increased binding to cultured endothelial cells. There was no relationship between activity of core 2 transferase and HbA(1c) (P = 0.8314), serum advanced glycation end product levels (P = 0.4159), age of the patient (P = 0.7896), and duration of diabetes (P = 0.3307). On the basis that branched O-glycans formed by the action of core 2 transferase participate in leukocyte adhesion, the present data suggest the involvement of this enzyme in increased leukocyte-endothelial cell adhesion and the pathogenesis of capillary occlusion in diabetic retinopathy.

Understanding E-Bike Users' Behaviour, Motives, and Barriers to the Use - An Empirical Study with high Potential for Mobility Management

A representative study among e-bike owners and tenants in Switzerland (n = 1652) provides a deeper understanding of e-bike users characteristics, motives, values, usage behavior, and barriers to the use. In a micro simulation the implications of the findings for the energy demand and CO2 emissions are estimated.

The benefits and pitfalls of language change – The case of gender-fair language use

Gender-fair language (GFL) is a symmetric linguistic treatment of women and men. To create GFL two principle strategies can be deployed. Neutralization means that gender-unmarked forms (police officer) are used to substitute the male-biased (policeman). Feminization, implies that feminine forms of nouns are used systematically to make female referents visible. The results of a comprehensive European research program provide evidence in support of a non-discrimination policy in language, yet identify the potential setbacks preventing linguistic reforms to be effective. In general, studies indicate positive effects of GFL. In an applied context, for example women feel more motivated to apply for the position if a job advertisement is formulated in a GFL. However, negative effects of reformed usage were also reported specifically when GFL is novel. For example, a woman referred to as a chairperson was evaluated lower in occupational status than a woman referred to as a chairman.

Investigating the potential of reported cattle mortality data in Switzerland for syndromic surveillance

Systems for the identification and registration of cattle have gradually been receiving attention for use in syndromic surveillance, a relatively recent approach for the early detection of infectious disease outbreaks. Real or near real-time monitoring of deaths or stillbirths reported to these systems offer an opportunity to detect temporal or spatial clusters of increased mortality that could be caused by an infectious disease epidemic. In Switzerland, such data are recorded in the "Tierverkehrsdatenbank" (TVD). To investigate the potential of the Swiss TVD for syndromic surveillance, 3 years of data (2009-2011) were assessed in terms of data quality, including timeliness of reporting and completeness of geographic data. Two time-series consisting of reported on-farm deaths and stillbirths were retrospectively analysed to define and quantify the temporal patterns that result from non-health related factors. Geographic data were almost always present in the TVD data; often at different spatial scales. On-farm deaths were reported to the database by farmers in a timely fashion; stillbirths were less timely. Timeliness and geographic coverage are two important features of disease surveillance systems, highlighting the suitability of the TVD for use in a syndromic surveillance system. Both time series exhibited different temporal patterns that were associated with non-health related factors. To avoid false positive signals, these patterns need to be removed from the data or accounted for in some way before applying aberration detection algorithms in real-time. Evaluating mortality data reported to systems for the identification and registration of cattle is of value for comparing national data systems and as a first step towards a European-wide early detection system for emerging and re-emerging cattle diseases.

Migration of C1 to C8 volatile organic compounds in sediments at DSDP Hole 75-530A

The distribution of C1 to C8 hydrocarbons in sediment samples from DSDP Leg 75, Hole 530A, indicates that significant amounts of methane and ethane have migrated from organic-rich to organic-lean shales in close proximity. Most compounds larger than ethane are not migrating out of black shales, where they occur in high concentrations. These results lead to a general model for assessing migration. In addition, three shale types are identified on the basis of organic carbon and pyrolysis products and patterns.

Energetic performance of landfill and digester biogas in a domestic cooker

The energetic performance of landfill biogas (LB) and biodigester biogas (BB) from municipal waste was examined in consumption tests. These tests were performed in situ at a gas generation plant associated with a landfill facility in Madrid (Spain) and following the standard UNE-EN 30-2-1 (1999). The jets of a domestic cooker commonly used for natural gas (NG) or liquefied petroleum gas (LPG) were modified to operate with the biogases produced at the facility. The working pressures best suited to the tested gases, i.e., to avoid flashback and flame lift, and to ensure the stability and correct functioning of the flame during combustion, were determined by trial and error. Both biogases returned optimum energetic performance for the transfer of heat to water in a metallic recipient (as required by the above standard) at a supply pressure of 10 mbar. Domestic cookers are normally supplied with NG at a pressure of 20 mbar, at which pressure the energetic performance of G20 reference gas was higher than that of both biogases (52.84% compared to 38.06% and 49.77% respectively). Data concerning these issues involving also unexplored feedstock are required for the correct conversions of domestic cookers in order to avoid risks of serious personal injuries or property damages.

Characterisation of the operation & maintenance phase in PV rural electrification programmes

Con 1.300 millones de personas en el mundo sin acceso a la electricidad (la mayoría en entornos rurales de países empobrecidos), la energía solar fotovoltaica constituye una solución viable técnica y económicamente para electrificar las zonas más remotas del planeta donde las redes eléctricas convencionales no llegan. Casi todos los países en el mundo han desarrollado algún tipo de programa de electrificación fotovoltaica rural durante los últimos 40 años, principalmente los países más pobres, donde a través de diferentes modelos de financiación, se han instalado millones de sistemas solares domiciliarios (pequeños sistemas fotovoltaicos para uso doméstico). Durante este largo período, se han ido superando muchas barreras, como la mejora de la calidad de los sistemas fotovoltaicos, la reducción de costes, la optimización del diseño y del dimensionado de los sistemas, la disponibilidad financiera para implantar programas de electrificación rural, etc. Gracias a esto, la electrificación rural descentralizada ha experimentado recientemente un salto de escala caracterizada por la implantación de grandes programas con miles de sistemas solares domiciliarios e integrando largos períodos de mantenimiento. Muchos de estos grandes programas se están llevando a cabo con limitado éxito, ya que generalmente parten de supuestos e hipótesis poco contrastadas con la realidad, comprometiendo así un retorno económico que permita el desarrollo de esta actividad a largo plazo. En este escenario surge un nuevo reto: el de cómo garantizar la sostenibilidad de los grandes programas de electrificación rural fotovoltaica. Se argumenta que la principal causa de esta falta de rentabilidad es el imprevisto alto coste de la fase de operación y mantenimiento. Cuestiones clave tales como la estructura de costes de operación y mantenimiento o la fiabilidad de los componentes del sistema fotovoltaico no están bien caracterizados hoy en día. Esta situación limita la capacidad de diseñar estructuras de mantenimiento capaces de asegurar la sostenibilidad y la rentabilidad del servicio de operación y mantenimiento en estos programas. Esta tesis doctoral tiene como objetivo responder a estas cuestiones. Se ha realizado varios estudios sobre la base de un gran programa de electrificación rural fotovoltaica real llevado a cabo en Marruecos con más de 13.000 sistemas solares domiciliarios instalados. Sobre la base de este programa se ha hecho una evaluación en profundidad de la fiabilidad de los sistemas solares a partir de los datos de mantenimiento recogidos durante 5 años con más de 80.000 inputs. Los resultados han permitido establecer las funciones de fiabilidad de los equipos tal y como se comportan en condiciones reales de operación, las tasas de fallos y los tiempos medios hasta el fallo para los principales componentes del sistema, siendo este el primer caso de divulgación de resultados de este tipo en el campo de la electrificación rural fotovoltaica. Los dos principales componentes del sistema solar domiciliario, la batería y el módulo fotovoltaico, han sido analizados en campo a través de una muestra de 41 sistemas trabajando en condiciones reales pertenecientes al programa solar marroquí. Por un lado se ha estudiado la degradación de la capacidad de las baterías y por otro la degradación de potencia de los módulos fotovoltaicos. En el caso de las baterías, los resultados nos han permitido caracterizar la curva de degradación en capacidad llegando a obtener una propuesta de nueva definición del umbral de vida útil de las baterías en electrificación rural. También sobre la base del programa solar de Marruecos se ha llevado a cabo un estudio de caracterización de los costes reales de operación y mantenimiento a partir de la base de datos de contabilidad del programa registrados durante 5 años. Los resultados del estudio han permitido definir cuáles son costes que más incidencia tienen en el coste global. Se han obtenido los costes unitarios por sistema instalado y se han calculado los montantes de las cuotas de mantenimiento de los usuarios para garantizar la rentabilidad de la operación y mantenimiento. Finalmente, se propone un modelo de optimización matemática para diseñar estructuras de mantenimiento basado en los resultados de los estudios anteriores. La herramienta, elaborada mediante programación lineal entera mixta, se ha aplicado al programa marroquí con el fin de validar el modelo propuesto. ABSTRACT With 1,300 million people worldwide deprived of access to electricity (mostly in rural environments), photovoltaic solar energy has proven to be a cost‐effective solution and the only hope for electrifying the most remote inhabitants of the planet, where conventional electric grids do not reach because they are unaffordable. Almost all countries in the world have had some kind of rural photovoltaic electrification programme during the past 40 years, mainly the poorer countries, where through different organizational models, millions of solar home systems (small photovoltaic systems for domestic use) have been installed. During this long period, many barriers have been overcome, such as quality enhancement, cost reduction, the optimization of designing and sizing, financial availability, etc. Thanks to this, decentralized rural electrification has recently experienced a change of scale characterized by new programmes with thousands of solar home systems and long maintenance periods. Many of these large programmes are being developed with limited success, as they have generally been based on assumptions that do not correspond to reality, compromising the economic return that allows long term activity. In this scenario a new challenge emerges, which approaches the sustainability of large programmes. It is argued that the main cause of unprofitability is the unexpected high cost of the operation and maintenance of the solar systems. In fact, the lack of a paradigm in decentralized rural services has led to many private companies to carry out decentralized electrification programmes blindly. Issues such as the operation and maintenance cost structure or the reliability of the solar home system components have still not been characterized. This situation does not allow optimized maintenance structure to be designed to assure the sustainability and profitability of the operation and maintenance service. This PhD thesis aims to respond to these needs. Several studies have been carried out based on a real and large photovoltaic rural electrification programme carried out in Morocco with more than 13,000 solar home systems. An in‐depth reliability assessment has been made from a 5‐year maintenance database with more than 80,000 maintenance inputs. The results have allowed us to establish the real reliability functions, the failure rate and the main time to failure of the main components of the system, reporting these findings for the first time in the field of rural electrification. Both in‐field experiments on the capacity degradation of batteries and power degradation of photovoltaic modules have been carried out. During the experiments both samples of batteries and modules were operating under real conditions integrated into the solar home systems of the Moroccan programme. In the case of the batteries, the results have enabled us to obtain a proposal of definition of death of batteries in rural electrification. A cost assessment of the Moroccan experience based on a 5‐year accounting database has been carried out to characterize the cost structure of the programme. The results have allowed the major costs of the photovoltaic electrification to be defined. The overall cost ratio per installed system has been calculated together with the necessary fees that users would have to pay to make the operation and maintenance affordable. Finally, a mathematical optimization model has been proposed to design maintenance structures based on the previous study results. The tool has been applied to the Moroccan programme with the aim of validating the model.

Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice.

Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD- 1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments.

Catalogue of additions to the manuscripts /

Mode of access: Internet.

Genetic analysis of resistance to root-lesion nematode (Pratylenchus thornei) in wheat

The inheritance of resistance to root-lesion nematode was investigated in five synthetic hexaploid wheat lines and two bread wheat lines using a half-diallel design of F-1 and F-2 crosses. The combining ability of resistance genes in the synthetic hexaploid wheat lines was compared with the performance of the bread wheat line 'GS50a', the source of resistance to Pratylenchus thornei used in Australian wheat breeding programmes. Replicated glasshouse trials identified P. thornei resistance as polygenic and additive in gene action. General combining ability (GCA) of the parents was more important than specific combining ability (SCA) effects in the inheritance of P. thornei resistance in both F-1 and F-2 populations. The synthetic hexaploid wheat line 'CPI133872' was identified as the best general combiner, however, all five synthetic hexaploid wheat lines possessed better GCA than 'GS50a'. The synthetic hexaploid wheat lines contain novel sources of P. thornei resistance that will provide alternative and more effective sources of resistance to be utilized in wheat breeding programmes.

Types of Addresses and Levels of use in the TCP/IP Protocol Stack

The publication comments on certain moments of the method of teaching the types of addresses and their use in the TCP/IP protocol stack.

Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

The contribution of higher education to economic *development in a globalized environment

Amidst concerns about achieving high levels of technology to remain competitive in the global market without compromising economic development, national economies are experiencing a high demand for human capital. As higher education is assumed to be the main source of human capital, this analysis focused on a more specific and less explored area of the generally accepted idea that higher education contributes to economic growth. The purpose of this study, therefore, was to find whether higher education also contributes to economic development, and whether that contribution is more substantial in a globalized context. ^ Consequently, a multiple linear regression analysis was conducted to support with statistical significance the answer to the research question: Does higher education contributes to economic development in the context of globalization? The information analyzed was obtained from historical data of 91 selected countries, and the period of time of the study was 10 years (1990–2000). Some variables, however, were lagged back 5, 10 or 15 years along a 15-year timeframe (1975–1990). The resulting comparative static model was based on the Cobb-Douglas production function and the Solow model to specify economic growth as a function of physical capital, labor, technology, and productivity. Then, formal education, economic development, and globalization were added to the equation. ^ The findings of this study supported the assumption that the independent contribution of the changes in higher education completion and globalization to changes in economic growth is more substantial than the contribution of their interaction. The results also suggested that changes in higher and secondary education completion contribute much more to changes in economic growth in less developed countries than in their more developed counterparts. ^ As a conclusion, based on the results of this study, I proposed the implementation of public policy in less developed countries to promote and expand adequate secondary and higher education systems with the purpose of helping in the achievement of economic development. I also recommended further research efforts on this topic to emphasize the contribution of education to the economy, mainly in less developed countries. ^