Showing papers by "University of Alcalá published in 2012"

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

Abstract: Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m 2 on day 1 plus docetaxel (75 mg/m 2 on day 1) or gemcitabine (1250 mg/m 2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m 2 or AUC 5 with gemcitabine 1000 mg/m 2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

U-Series Dating of Paleolithic Art in 11 Caves in Spain

Abstract: Paleolithic cave art is an exceptional archive of early human symbolic behavior, but because obtaining reliable dates has been difficult, its chronology is still poorly understood after more than a century of study. We present uranium-series disequilibrium dates of calcite deposits overlying or underlying art found in 11 caves, including the United Nations Educational, Scientific, and Cultural Organization (UNESCO) World Heritage sites of Altamira, El Castillo, and Tito Bustillo, Spain. The results demonstrate that the tradition of decorating caves extends back at least to the Early Aurignacian period, with minimum ages of 40.8 thousand years for a red disk, 37.3 thousand years for a hand stencil, and 35.6 thousand years for a claviform-like symbol. These minimum ages reveal either that cave art was a part of the cultural repertoire of the first anatomically modern humans in Europe or that perhaps Neandertals also engaged in painting caves.

Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society

Abstract: Background Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age. Methods We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of hirsutism. Results The prevalence of hirsutism is ~10% in most populations, with the important exception of Far-East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention. Conclusions Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint.

A DNA methylation fingerprint of 1628 human samples

Abstract: Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number of human samples and pathological conditions. Herein, we present a compromise between an extremely comprehensive study of a human sample population with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1628 human samples in which we interrogated 1505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG-island hypermethylation and a loss of CpG methylation in non-CpG-island promoters. Although transformed cells are those in which DNA methylation disruption is more obvious, we observed that other common human diseases, such as neurological and autoimmune disorders, had their own distinct DNA methylation profiles. Most importantly, we provide proof of principle that the DNA methylation fingerprints obtained might be useful for translational purposes by showing that we are able to identify the tumor type origin of cancers of unknown primary origin (CUPs). Thus, the DNA methylation patterns identified across the largest spectrum of samples, tissues, and diseases reported to date constitute a baseline for developing higher-resolution DNA methylation maps and provide important clues concerning the contribution of CpG methylation to tissue identity and its changes in the most prevalent human diseases.

Superhydrophobic alkanethiol-coated microsubmarines for effective removal of oil.

Abstract: We demonstrate the use of artificial nanomachines for effective interaction, capture, transport, and removal of oil droplets. The simple nanomachine-enabled oil collection method is based on modifying microtube engines with a superhydrophobic layer able to adsorb oil by means of its strong adhesion to a long chain of self-assembled monolayers (SAMs) of alkanethiols created on the rough gold outer surface of the device. The resultant SAM-coated Au/Ni/PEDOT/Pt microsubmarine displays continuous interaction with large oil droplets and is capable of loading and transporting multiple small oil droplets. The influence of the alkanethiol chain length, polarity, and head functional group and hence of the surface hydrophobicity upon the oil–nanomotor interaction and the propulsion is examined. No such oil–motor interactions were observed in control experiments involving both unmodified microengines and microengines coated with SAM layers containing a polar terminal group. These results demonstrate that such SAM-Au...

REMS: The Environmental Sensor Suite for the Mars Science Laboratory Rover

Abstract: The Rover Environmental Monitoring Station (REMS) will investigate environmental factors directly tied to current habitability at the Martian surface during the Mars Science Laboratory (MSL) mission. Three major habitability factors are addressed by REMS: the thermal environment, ultraviolet irradiation, and water cycling. The thermal environment is determined by a mixture of processes, chief amongst these being the meteorological. Accordingly, the REMS sensors have been designed to record air and ground temperatures, pressure, relative humidity, wind speed in the horizontal and vertical directions, as well as ultraviolet radiation in different bands. These sensors are distributed over the rover in four places: two booms located on the MSL Remote Sensing Mast, the ultraviolet sensor on the rover deck, and the pressure sensor inside the rover body. Typical daily REMS observations will collect 180 minutes of data from all sensors simultaneously (arranged in 5 minute hourly samples plus 60 additional minutes taken at times to be decided during the course of the mission). REMS will add significantly to the environmental record collected by prior missions through the range of simultaneous observations including water vapor; the ability to take measurements routinely through the night; the intended minimum of one Martian year of observations; and the first measurement of surface UV irradiation. In this paper, we describe the scientific potential of REMS measurements and describe in detail the sensors that constitute REMS and the calibration procedures.

Measurement of the proton-air cross section at √s=57 TeV with the Pierre Auger Observatory.

Abstract: We report a measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57 TeV. This is derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory: systematic uncertainties are studied in detail. Analyzing the tail of the distribution of the shower maxima, a proton-air cross section of [505 +/- 22(stat)(-36)(+28)(syst)] mb is found.

Emerging perspectives in the restoration of biodiversity-based ecosystem services

Abstract: Given the large-scale anthropogenic alteration of natural habitats, ecological restoration is emerging as one of the most important disciplines in environmental science. Once habitats are physically restored, an important goal of restoration is to recover the ecosystem services provided by the diversity of species and their interactions (e.g., seed dispersal, pollination, pest control, and invasion resistance). However, current understanding of the ecological processes underlying this recovery is often incomplete and poorly integrated across different ecosystems. Here, we highlight recent conceptual findings in biodiversity–ecosystem functioning, food-web theory, and metacommunity theory that are relevant to restoration. We also identify knowledge gaps that will contribute to moving restoration from a site- and situation-specific discipline to a more globally applicable science.

Restoration of Biodiversity and Ecosystem Services on Agricultural Land

Abstract: Cultivation and cropping are major causes of destruction and degradation of natural ecosystems throughout the world. We face the challenge of maintaining provisioning services while conserving or enhancing other ecosystem services and biodiversity in agricultural landscapes. There is a range of possibilities within two types of intervention, namely “land sharing” and “land separation”; the former advocates the enhancement of the farmed environment, but the latter a separation between land designated for farming versus conservation. Land sharing may involve biodiversity-based agricultural practices, learning from traditional farming, changing from conventional to organic agriculture and from “simple” crops and pastures to agro-forestry systems, and restoring or creating specific elements to benefit wildlife and particular services without decreasing agricultural production. Land separation in the farmland context involves restoring or creating non-farmland habitat at the expense of field-level agricultural production—for example, woodland on arable land. Restoration by land sharing has the potential to enhance agricultural production, other ecosystem services and biodiversity at both the field and landscape scale; however, restoration by land separation would provide these benefits only at the landscape scale. Although recent debate has contrasted these approaches, we suggest they should be used in combination to maximize benefits. Furthermore, we suggest “woodland islets”, an intermediate approach between land abandonment and farmland afforestation, for ecological restoration in extensive agricultural landscapes. This approach allows reconciliation of farmland production, conservation of values linked to cultural landscapes, enhancement of biodiversity, and provision of a range of ecosystem services. Beyond academic research, restoration projects within agricultural landscapes are essential if we want to halt environmental degradation and biodiversity loss.

Developmental changes in mesophyll diffusion conductance and photosynthetic capacity under different light and water availabilities in Populus tremula: how structure constrains function.

Abstract: Finite mesophyll diffusion conductance (gm) significantly constrains net assimilation rate (An), but gm variations and variation sources in response to environmental stresses during leaf development are imperfectly known. The combined effects of light and water limitations on gm and diffusion limitations of photosynthesis were studied in saplings of Populus tremula L. An one-dimensional diffusion model was used to gain insight into the importance of key anatomical traits in determining gm. Leaf development was associated with increases in dry mass per unit area, thickness, density, exposed mesophyll (Smes/S) and chloroplast (Sc/S) to leaf area ratio, internal air space (fias), cell wall thickness and chloroplast dimensions. Development of Smes/S and Sc/S was delayed under low light. Reduction in light availability was associated with lower Sc/S, but with larger fias and chloroplast thickness. Water stress reduced Sc/S and increased cell wall thickness under high light. In all treatments, gm and An increased and CO2 drawdown because of gm, Ci–Cc, decreased with increasing leaf age. Low light and drought resulted in reduced gm and An and increased Ci–Cc. These results emphasize the importance of gm and its components in determining An variations during leaf development and in response to stress.

UAV Attitude Estimation Using Unscented Kalman Filter and TRIAD

Abstract: A main problem in autonomous vehicles in general, and in unmanned aerial vehicles (UAVs) in particular, is the determination of the attitude angles. A novel method to estimate these angles using off-the-shelf components is presented. This paper introduces an attitude heading reference system (AHRS) based on the unscented Kalman filter (UKF) using the three-axis attitude determination (TRIAD) algorithm as the observation model. The performance of the method is assessed through simulations and compared to an AHRS based on the extended Kalman filter (EKF). The paper presents field experiment results using a real fixed-wing UAV. The results show good real-time performance with low computational cost in a microcontroller.

The role of health extension workers in improving utilization of maternal health services in rural areas in Ethiopia: a cross sectional study

Abstract: Community health workers are widely used to provide care for a broad range of health issues. Since 2003 the government of Ethiopia has been deploying specially trained new cadres of community based health workers named health extension workers (HEWs). This initiative has been called the health extension program. Very few studies have investigated the role of these community health workers in improving utilization of maternal health services. A cross sectional survey of 725 randomly selected women with under-five children from three districts in Northern Ethiopia. We investigated women’s utilization of family planning, antenatal care, birth assistance, postnatal care, HIV testing and use of iodized salt and compared our results to findings of a previous national survey from 2005. In addition, we investigated the association between several variables and utilization of maternal health services using logistic regression analysis. HEWs have contributed substantially to the improvement in women’s utilization of family planning, antenatal care and HIV testing. However, their contribution to the improvement in health facility delivery, postnatal check up and use of iodized salt seems insignificant. Women who were literate (OR, 1.85), listened to the radio (OR, 1.45), had income generating activities (OR, 1.43) and had been working towards graduation or graduated as model family (OR, 2.13) were more likely to demonstrate good utilization of maternal health services. A model family is by definition a family which has fulfilled all the packages of the HEP. The HEWs seem to have substantial contribution in several aspects of utilization of maternal health services but their insignificant contribution in improving health facility delivery and skilled birth attendance remains an important problem. More effort is needed to improve the effectiveness of HEWs in these regards. For example, strengthening HEWs’ support for pregnant women for birth planning and preparedness and referral from HEWs to midwives at health centers should be strengthened. In addition, women’s participation in income generating activities, access to radio and education could be targets for future interventions.

Shaping, organizing, and rethinking service innovation: a multidimensional framework

Abstract: Purpose – The purpose of this paper is to review key research contributions that may be useful for rethinking service innovation. Service innovation is not a monolithic construct; therefore, the opportunities for further research are multidimensional and interdisciplinary.Design/methodology/approach – A summary analysis of extant literature identifies valuable contributions and fundamental methodological issues from various perspectives. The proposed directions for future research entail where to innovate, how to innovate, and what to innovate in services.Findings – The analysis and discussion lead to a multidimensional framework of service innovation, with a particular emphasis on organizational and customer cocreation perspectives.Practical implications – This article contains guidelines and real‐world examples to help practitioners and policy makers develop service innovation strategies through the consideration of different levels, organizations, and perspectives.Originality/value – This article offer...

Herschel/PACS spectroscopy of NGC 4418 and Arp 220: H2O, H218O, OH, 18OH, O I, HCN, and NH3

Abstract: Full range Herschel/PACS spectroscopy of the (ultra)luminous infrared galaxies NGC 4418 and Arp 220, observed as part of the SHINING key programme, reveals high excitation in H2O, OH, HCN, and NH3. In NGC 4418, absorption lines were detected with Elower > 800 K (H2O), 600 K (OH), 1075 K (HCN), and 600 K (NH3), while in Arp 220 the excitation is somewhat lower. While outflow signatures in moderate excitation lines are seen in Arp 220 as have been seen in previous studies, in NGC 4418 the lines tracing its outer regions are redshifted relative to the nucleus, suggesting an inflow with u M 12 Myr −1 . Both galaxies have compact and warm (Tdust 100 K) nuclear continuum components, together with a more extended and colder component that is much more prominent and massive in Arp 220. A chemical dichotomy is found in both sources: on the one hand, the nuclear regions have high H2O abundances, ∼10 −5 , and high HCN/H2 Oa nd HCN/NH3 column density ratios of 0.1−0.4 and 2−5, respectively, indicating a chemistry typical of evolved hot cores where grain mantle evaporation has occurred. On the other hand, the high OH abundance, with OH/H2O ratios of ∼0.5, indicates the effects of X-rays and/or cosmic rays. The nuclear media have high surface brightnesses (10 13 L� /kpc 2 ) and are estimated to be very thick (NH 10 25 cm −2 ). While NGC 4418 shows weak absorption in H 18 Oa nd 18 OH, with a 16 O-to- 18 O ratio of 250−500, the relatively strong absorption of the rare isotopologues in Arp 220 indicates 18 O enhancement, with 16 O-to- 18 Oo f 70−130. Further away from the nuclear regions, the H2O abundance decreases to 10 −7 and the OH/H2O ratio is reversed relative to the nuclear region to 2.5−10. Despite the different scales and morphologies of NGC 4418, Arp 220, and Mrk 231, preliminary evidence is found for an evolutionary sequence from infall, hot-core like chemistry, and solar oxygen isotope ratio to high velocity outflow, disruption of the hot core chemistry and cumulative high mass stellar processing of 18 O.

A bibliometric study

Abstract: El objetivo del presente estudio es analizar la participacion de los paises iberoamericanos en la literatura cientifica internacional, su evolucion, la colaboracion con terceros paises e instituciones y -muy especialmente- el papel de Espana en el panorama cientifico iberoamericano. Los datos muestran un claro liderazgo de Brasil, que durante el periodo analizado participo en el 45% de los articulos publicados (a partir de 2007, su participacion supera el 50%). La institucion iberoamericana con mayor numero de publicaciones es la Universidad de Sao Paulo. Como era de esperarse, el pais no iberoamericano que mas aparece como co-firmante es los Estados Unidos, que esta presente en el 13% de las publicaciones. Espana mantiene el segundo puesto, seguida de Francia y el Reino Unido. Las instituciones de terceros paises con mayor participacion numerica en las publicaciones de paises iberoamericanos son la Universidad de California y el Consejo Superior de Investigaciones Cientificas de Espana, en ese orden. Es importante destacar el hecho de que algunas de las publicaciones con mayor numero de citas y co-firmadas por autores iberoamericanos han sido lideradas por cientificos espanoles. Palabras clave: Iberoamerica, publicaciones cientificas, evolucion, colaboracion This article aims to analyse the participation of Ibero-American (Spanish and Portuguese speaking) countries in the international scientific literature, as well as its evolution, its collaboration with non Ibero-American scientists and institutions, with an emphasis on the role of Spain in the Ibero-America scientific scenario. During the period of time that was considered, Brazil has participated in 45% of the total Ibero-American publications, with a continuous increasing growth: since 2007 this participation raised to above 50%. The most productive institution is the University of Sao Paulo. As expected, scientists from the United States are the most commonly found as co-authors in publications with Ibero-American authors (13%), followed by those from Spain, France and the United Kingdom. Similarly, the non-Ibero-American organization with the highest presence is the University of California, followed by the Spanish Consejo Superior de Investigaciones Cientificas. It is also remarkable that some of the most cited publications of IberoAmerican co-authors have scientists from Spain as corresponding authors.

Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice

Abstract: Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5flox/flox mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases.

Predictable changes in aboveground allometry of trees along gradients of temperature, aridity and competition

Abstract: Aim Trees are often observed to get shorter and more narrowly crowned in dry regions and at high elevations. We explore how this pattern is driven by two opposing factors: competition for light makes it advantageous to extend branches to their biomechanical limit, whereas under cold or arid conditions it is advantageous to have shorter branches, thereby reducing the length of the hydraulic transport system and embolism risk. Using data from 700,000 trees of 26 species, we quantify how environmental conditions influence the scaling of height and crown diameter (CD) with stem diameter (d.b.h.). We compare our predictions with those of metabolic scaling theory (MST), which suggests that allometry is invariant of environment. Location 48,000 inventory plots that systematically sample mainland Spain, a region in which climate varies strongly. Methods We fit d.b.h.–height and d.b.h.–CD functions using Bayesian methods, allowing comparison of within- and across-species trends in allometry along gradients of temperature, precipitation, drought and competition for light (i.e. the basal area of taller trees). Results The competitive environment had a strong influence on aboveground allometry, but all trees were far shorter than predicted by biomechanical models, suggesting that factors other than biomechanics are important. Species that dominate in arid and cold habitats were much shorter (for a given diameter) than those from benign conditions; but within-species heights did not vary strongly across climatic gradients. Main conclusions Our results do not support the MST prediction that d.b.h.–height and d.b.h.–CD allometries are invariant, or that biomechanical constraints determine height allometry. Rather, we highlight the role of hydraulic limitations in this region. The fact that intra-specific adjustment in d.b.h.–CD – height allometry along environmental gradients was far weaker than across-species changes may indicate genetic constraints on allometry which might contribute to niche differentiation among species.

Increase in size and nitrogen concentration enhances seedling survival in Mediterranean plantations. Insights from an ecophysiological conceptual model of plant survival

Abstract: Reduction in size and tissue nutrient concentration is widely considered to increase seedling drought resistance in dry and oligotrophic plantation sites. However, much evidence indicates that increase in size and tissue nutrient concentration improves seedling survival in Mediterranean forest plantations. This suggests that the ecophysiological processes and functional attributes relevant for early seedling survival in Mediterranean climate must be reconsidered. We propose a ecophysiological conceptual model for seedling survival in Mediterranean-climate plantations to provide a physiological explanation of the frequent positive relationship between outplanting performance and seedling size and nutrient concentration. The model considers the physiological processes outlined in the plantation establishment model of Burdett (Can J For Res 20:415–427, 1990), but incorporates other physiological processes that drive seedling survival, such as N remobilization, carbohydrate storage and plant hydraulics. The model considers that seedling survival in Mediterranean climates is linked to high growth capacity during the wet season. The model is for container plants and is based on three main principles, (1) Mediterranean climates are not dry the entire year but usually have two seasons of contrasting water availability; (2) summer drought is the main cause of seedling mortality; in this context, deep and large roots is a key trait for avoiding lethal water stress; (3) attainment of large root systems in the dry season is promoted when seedlings have high growth during the wet season. High growth is achieved when seedlings can divert large amount of resources to support new root and shoot growth. Functional traits that confer high photosynthesis, nutrient remobilization capacity, and non-structural carbohydrate storage promote high growth. Increases in seedling size and nutrient concentration strongly affect these physiological processes. Traits that confer high drought resistance are of low value during the wet season because hinder growth capacity. We provide specific evidence to support the model and finally we discuss its implications and the factors that may alter the frequent increase in performance with increase in seedling size and tissue nutrient concentration.

Assisting the Visually Impaired: Obstacle Detection and Warning System by Acoustic Feedback

Abstract: The aim of this article is focused on the design of an obstacle detection system for assisting visually impaired people. A dense disparity map is computed from the images of a stereo camera carried by the user. By using the dense disparity map, potential obstacles can be detected in 3D in indoor and outdoor scenarios. A ground plane estimation algorithm based on RANSAC plus filtering techniques allows the robust detection of the ground in every frame. A polar grid representation is proposed to account for the potential obstacles in the scene. The design is completed with acoustic feedback to assist visually impaired users while approaching obstacles. Beep sounds with different frequencies and repetitions inform the user about the presence of obstacles. Audio bone conducting technology is employed to play these sounds without interrupting the visually impaired user from hearing other important sounds from its local environment. A user study participated by four visually impaired volunteers supports the proposed system.

Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.

Abstract: BACKGROUND AND PURPOSE The sigma-1 (σ(1) ) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ(1) receptor ligands used as pharmacological tools are unclear and the demonstration that σ(1) receptor antagonists have efficacy in reversing central sensitization-related pain sensitivity is still missing. EXPERIMENTAL APPROACH The pharmacological properties of a novel σ(1) receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ(1) receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ(1) receptor occupancy were measured to substantiate behavioural data. KEY RESULTS Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of σ(1) receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve-injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ(1) receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. CONCLUSIONS AND IMPLICATIONS These findings contribute to evidence identifying the σ(1) receptor as a modulator of activity-induced spinal sensitization and pain hypersensitivity, and suggest σ(1) receptor antagonists as potential novel treatments for neuropathic pain.

Mir-33 regulates cell proliferation and cell cycle progression.

Abstract: Cholesterol metabolism is tightly regulated at the cellular level and is essential for cellular growth. microRNAs (miRNAs), a class of noncoding RNAs, have emerged as critical regulators of gene expression, acting predominantly at posttranscriptional level. Recent work from our group and others has shown that hsa-miR-33a and hsa-miR-33b, miRNAs located within intronic sequences of the Srebp genes, regulate cholesterol and fatty acid metabolism in concert with their host genes. Here, we show that hsa-miR-33 family members modulate the expression of genes involved in cell cycle regulation and cell proliferation. MiR-33 inhibits the expression of the cyclin-dependent kinase 6 (CDK6) and cyclin D1 (CCND1), thereby reducing cell proliferation and cell cycle progression. Overexpression of miR-33 induces a significant G 1 cell cycle arrest in Huh7 and A549 cell lines. Most importantly, inhibition of miR-33 expression using 2'fluoro/methoxyethyl-modified (2'F/MOE-modified) phosphorothioate backbone antisense oligonucleotides improves liver regeneration after partial hepatectomy (PH) in mice, suggesting an important role for miR-33 in regulating hepatocyte proliferation during liver regeneration. Altogether, these results suggest that Srebp/miR-33 locus may cooperate to regulate cell proliferation, cell cycle progression and may also be relevant to human liver regeneration.

From climate change impacts to the development of adaptation strategies: Challenges for agriculture in Europe

Abstract: This study links climate change impacts to the development of adaptation strategies for agriculture in Europe. Climate change is expected to intensify the existing risks, particularly in southern regions, and create new opportunities in some northern areas. These risks and opportunities are characterised and interpreted across European regions by analysing over 300 highly relevant publications that appeared in the last decade. The result is a synthesis of the reasons for concern for European agricultural regions. The need to respond to these risks and opportunities is addressed by evaluating the costs and benefits of a number of technical and policy actions. The results highlight the importance of enhanced water use efficiency as a critical response to climate risks and the need for a more effective extension service. These results aim to assist stakeholders as they take up the adaptation challenge and develop measures to reduce the vulnerability of the sector to climate change.

Next-generation sequencing and syntenic integration of flow-sorted arms of wheat chromosome 4A exposes the chromosome structure and gene content.

Abstract: Wheat is the third most important crop for human nutrition in the world. The availability of high-resolution genetic and physical maps and ultimately a complete genome sequence holds great promise for breeding improved varieties to cope with increasing food demand under the conditions of changing global climate. However, the large size of the bread wheat (Triticum aestivum) genome (approximately 17 Gb/1C) and the triplication of genic sequence resulting from its hexaploid status have impeded genome sequencing of this important crop species. Here we describe the use of mitotic chromosome flow sorting to separately purify and then shotgun-sequence a pair of telocentric chromosomes that together form chromosome 4A (856 Mb/1C) of wheat. The isolation of this much reduced template and the consequent avoidance of the problem of sequence duplication, in conjunction with synteny-based comparisons with other grass genomes, have facilitated construction of an ordered gene map of chromosome 4A, embracing ≥85% of its total gene content, and have enabled precise localization of the various translocation and inversion breakpoints on chromosome 4A that differentiate it from its progenitor chromosome in the A genome diploid donor. The gene map of chromosome 4A, together with the emerging sequences of homoeologous wheat chromosome groups 4, 5 and 7, represent unique resources that will allow us to obtain new insights into the evolutionary dynamics between homoeologous chromosomes and syntenic chromosomal regions.

Antennas for the detection of radio emission pulses from cosmic-ray induced air showers at the Pierre Auger Observatory

Abstract: The Pierre Auger Observatory is exploring the potential of the radio detection technique to study extensive air showers induced by ultra-high energy cosmic rays. The Auger Engineering Radio Array (AERA) addresses both technological and scientific aspects of the radio technique. A first phase of AERA has been operating since September 2010 with detector stations observing radio signals at frequencies between 30 and 80 MHz. In this paper we present comparative studies to identify and optimize the antenna design for the final configuration of AERA consisting of 160 individual radio detector stations. The transient nature of the air shower signal requires a detailed description of the antenna sensor. As the ultra-wideband reception of pulses is not widely discussed in antenna literature, we review the relevant antenna characteristics and enhance theoretical considerations towards the impulse response of antennas including polarization effects and multiple signal reflections. On the basis of the vector effective length we study the transient response characteristics of three candidate antennas in the time domain. Observing the variation of the continuous galactic background intensity we rank the antennas with respect to the noise level added to the galactic signal.