Chemical sensors and biosensors in liquid environment based on microcantilevers with amplified quality factors

Póster presentado al 1st Senspol Workshop: SENSPOL European Thematic Network (EC Environmental and Climate Programma) Sensing Technologies for Contaminated Sites and Groundwater celebrado en Alcala de Henares (Madrid-España) en 2001.Peer reviewe

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Globally aligned photomosaic of the Lucky Strike hydrothermal vent field (Mid-Atlantic Ridge, 37°18.5′N) : release of georeferenced data, mosaic construction, and viewing software

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q12009, doi:10.1029/2008GC002204.We present a georeferenced photomosaic of the Lucky Strike hydrothermal vent field (Mid-Atlantic Ridge, 37°18′N). The photomosaic was generated from digital photographs acquired using the ARGO II seafloor imaging system during the 1996 LUSTRE cruise, which surveyed a ∼1 km2 zone and provided a coverage of ∼20% of the seafloor. The photomosaic has a pixel resolution of 15 mm and encloses the areas with known active hydrothermal venting. The final mosaic is generated after an optimization that includes the automatic detection of the same benthic features across different images (feature-matching), followed by a global alignment of images based on the vehicle navigation. We also provide software to construct mosaics from large sets of images for which georeferencing information exists (location, attitude, and altitude per image), to visualize them, and to extract data. Georeferencing information can be provided by the raw navigation data (collected during the survey) or result from the optimization obtained from image matching. Mosaics based solely on navigation can be readily generated by any user but the optimization and global alignment of the mosaic requires a case-by-case approach for which no universally software is available. The Lucky Strike photomosaics (optimized and navigated-only) are publicly available through the Marine Geoscience Data System (MGDS, http://www.marine-geo.org). The mosaic-generating and viewing software is available through the Computer Vision and Robotics Group Web page at the University of Girona (http://eia.udg.es/∼rafa/mosaicviewer.html).This work has been supported by the EU Marie Curie RTNs MOMARNet (OD, RG, JE, LN, JF, NG) and FREESUBNet (RG, NG, XC), the Spanish Ministry of Science and Innovation (grant CTM2007–64751; RG, JE), CNRS and ANR (grant ANR NT05–3_42212, JE), ICREA (LN), and by the Generalitat de Catalunya (JE, RG). JF has been funded by MICINN under FPI grant BES-2006-12733 and NG has been supported by MICINN under the ‘‘Ramon y Cajal’’ program

Lost in translation: Returning germline genetic results in genome-scale cancer research

Background: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. Methods: We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predisposition to PC or medium-high penetrance genes with well-defined cancer associated syndromes or phenotypes. Variants from candidate genes were annotated and classified according to international guidelines. Variants were considered actionable if clinical utility was established, with regard to prevention, diagnosis, prognostication and/or therapy. Results: A total of 48,904 germline variants were identified, with 2356 unique variants undergoing annotation and in silico classification. Twenty cases were deemed actionable and were returned via previously described RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of our cohort experienced clinical benefit from RoR. Conclusion: Returning research results within the context of large-scale genomics research is a labour-intensive, highly variable, complex operation. Results that warrant action are not infrequent, but the prevalence of those who experience a clinical difference as a result of returning individual results is currently low

Will opposites attract? Similarities and differences in students' perceptions of the stereotype profiles of other health and social care professional groups

The extent to which health and social care (HSC) students hold stereotypical views of other HSC professional groups is of great potential importance to team working in health care. This paper explores students' perceptions of different HSC professional groups at the beginning of their university programmes. Findings are presented from an analysis of baseline data collected as part of the New Generation Project longitudinal cohort study which is assessing the impact of interprofessional education over time on a range of variables including stereotyping. Questionnaires were administered to a cohort of over 1200 students from 10 different HSC professional groups entering their first year of university. Stereotypes were measured using a tool adapted from Barnes et al. (2000) designed to elicit stereotype ratings on a range of nine characteristics. The findings confirm that students arrive at university with an established and consistent set of stereotypes about other health and social care professional groups. Stereotypical profiles were compiled for each professional group indicating the distinctive characteristics of the groups as well as the similarities and differences between groups. Midwives, social workers and nurses were rated most highly on interpersonal skills and on being a team player whilst doctors were rated most highly on academic ability. Doctors, midwives and social workers were perceived as having the strongest leadership role, whilst doctors were also rated most highly on decision making. All professions were rated highly on confidence and professional competence and, with the exception of social workers, on practical skills. A comparison of profiles for each professional group reveals that, for example, pharmacists and doctors were perceived as having very similar characteristics as were social workers, midwives and nurses. However, the profiles of nurses and doctors were perceived to be very different. The implications of these similarities and differences are discussed in terms of their potential impact on interprofessional interactions, role boundaries and team working

Psychometric properties of Greek versions of the Modified Corah Dental Anxiety Scale (MDAS) and the Dental Fear Survey (DFS)

Background: A growing body of literature describes the performance of dental fear questionnaires in various countries. We describe the psychometric properties of Greek versions of the Modified Dental Anxiety Scale (MDAS) and the Dental Fear Survey (DFS) in adult Greek patients. Methods: Greek versions of the MDAS and DFS were administered to two samples of adult dental patients. In the first sample, 195 patients attending one of three private practice dental offices in a large city in Greece completed the questionnaires in the waiting room before dental treatment. After treatment, their dentists (who did not know how the patients had answered the questionnaire) rated their anxiety during dental treatment. In the second sample, 41 patients attending a Greek university dental school clinic completed the questionnaire twice at two separate visits, in order to provide test-retest data. Cronbach's alpha was used to compute the internal consistencies, while Spearman's rho was used to compute the testretest reliabilities. Construct validity was assessed by correlating the responses to the MDAS and DFS by Spearman's rho. Spearman's rho was also used to examine the criterion validities, by comparing the questionnaire responses with the dentists' ratings of anxiety. Results: The internal consistencies for the MDAS were 0.90 and 0.92 in the two samples; for the DFS, the internal consistencies were 0.96 in both samples. The test-retest reliabilities were 0.94 for the MDAS and 0.95 for the DFS. The correlation between the two questionnaires was 0.89. The patients' responses to both questionnaires were significantly related to the dentists' ratings of their anxiety during dental treatment (both p values less than 0.001). Conclusion: The results indicate that the Greek versions of the MDAS and DFS have good internal consistencies and test-retest reliabilities, as well as good construct and criterion validities. The psychometric properties of the Greek versions of these questionnaires appear to be similar to those previously reported in other countries.This research was supported by NIH/NIDCR grant T32DE07132

United States contributions to the Second International Indian Ocean Expedition (US IIOE-2)

From the Preface: The purpose of this document is to motivate and coordinate U.S. participation in the Second International Indian Ocean Expedition (IIOE-2) by outlining a core set of research priorities that will accelerate our understanding of geologic, oceanic, and atmospheric processes and their interactions in the Indian Ocean. These research priorities have been developed by the U.S. IIOE-2 Steering Committee based on the outcomes of an interdisciplinary Indian Ocean science workshop held at the Scripps Institution of Oceanography on September 11-13, 2017. The workshop was attended by 70 scientists with expertise spanning climate, atmospheric sciences, and multiple sub-disciplines of oceanography. Workshop participants were largely drawn from U.S. academic institutions and government agencies, with a few experts invited from India, China, and France to provide a broader perspective on international programs and activities and opportunities for collaboration. These research priorities also build upon the previously developed International IIOE-2 Science Plan and Implementation Strategy. Outcomes from the workshop are condensed into five scientific themes: Upwelling, inter-ocean exchanges, monsoon dynamics, inter-basin contrasts, marine geology and the deep ocean. Each theme is identified with priority questions that the U.S. research community would like to address and the measurements that need to be made in the Indian Ocean to address them.We thank the following organizations and programs for financial contributions, support and endorsement: the U.S. National Oceanic and Atmospheric Administration; the U.S. Ocean Carbon and Biogeochemistry program funded by the National Science Foundation and the National Aeronautics and Space Administration; the NASA Physical Oceanography Program; Scripps Institution of Oceanography; and the Indo-US Science and Technology Forum