123 resultados para Recognition ethics


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Genetic relatedness of the mound-building ant Formica pratensis was determined by means of microsatellite DNA polymorphism, and its impact on nestmate recognition was tested in a population in Southern Sweden (Oeland). Recognition between nests was measured by testing aggression levels between single pairs of workers. The genetic distances of nests (Nei's genetic distance) and the spatial distance of nests were correlated and both showed a strong relation to the aggression behavior. Multiple regression analysis revealed a stronger impact of genetic relatedness rather than spatial distances on aggression behavior. Neighbouring nests were more closely related than distant nests, which may reflect budding as a possible spreading mechanism. The genetic distance data showed that nestmate recognition was strongly genetically influenced in F. pratensis.

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Dendritic cells (DCs) are essential antigen-presenting cells for the induction of immunity against pathogens. However, HIV-1 spread is strongly enhanced in clusters of DCs and CD4(+) T cells. Uninfected DCs capture HIV-1 and mediate viral transfer to bystander CD4(+) T cells through a process termed trans-infection. Initial studies identified the C-type lectin DC-SIGN as the HIV-1 binding factor on DCs, which interacts with the viral envelope glycoproteins. Upon DC maturation, however, DC-SIGN is down-regulated, while HIV-1 capture and trans-infection is strongly enhanced via a glycoprotein-independent capture pathway that recognizes sialyllactose-containing membrane gangliosides. Here we show that the sialic acid-binding Ig-like lectin 1 (Siglec-1, CD169), which is highly expressed on mature DCs, specifically binds HIV-1 and vesicles carrying sialyllactose. Furthermore, Siglec-1 is essential for trans-infection by mature DCs. These findings identify Siglec-1 as a key factor for HIV-1 spread via infectious DC/T-cell synapses, highlighting a novel mechanism that mediates HIV-1 dissemination in activated tissues.

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EXECUTIVE SUMMARY This PhD research, funded by the Swiss Sciences Foundation, is principally devoted to enhance the recognition, the visualisation and the characterization of geobodies through innovative 3D seismic approaches. A series of case studies from the Australian North West Shelf ensures the development of reproducible integrated 3D workflows and gives new insight into local and regional stratigraphic as well as structural issues. This project was initiated in year 2000 at the Geology and Palaeontology Institute of the University of Lausanne (Switzerland). Several collaborations ensured the improvement of technical approaches as well as the assessment of geological models. - Investigations into the Timor Sea structural style were carried out at the Tectonics Special Research Centre of the University of Western Australia and in collaboration with Woodside Energy in Perth. - Seismic analysis and attributes classification approach were initiated with Schlumberger Oilfield Australia in Perth; assessments and enhancements of the integrated seismic approaches benefited from collaborations with scientists from Schlumberger Stavanger Research (Norway). Adapting and refining from "linear" exploration techniques, a conceptual "helical" 3D seismic approach has been developed. In order to investigate specific geological issues this approach, integrating seismic attributes and visualisation tools, has been refined and adjusted leading to the development of two specific workflows: - A stratigraphic workflow focused on the recognition of geobodies and the characterization of depositional systems. Additionally, it can support the modelling of the subsidence and incidentally the constraint of the hydrocarbon maturity of a given area. - A structural workflow used to quickly and accurately define major and secondary fault systems. The integration of the 3D structural interpretation results ensures the analysis of the fault networks kinematics which can affect hydrocarbon trapping mechanisms. The application of these integrated workflows brings new insight into two complex settings on the Australian North West Shelf and ensures the definition of astonishing stratigraphic and structural outcomes. The stratigraphic workflow ensures the 3D characterization of the Late Palaeozoic glacial depositional system on the Mermaid Nose (Dampier Subbasin, Northern Carnarvon Basin) that presents similarities with the glacial facies along the Neotethys margin up to Oman (chapter 3.1). A subsidence model reveals the Phanerozoic geodynamic evolution of this area (chapter 3.2) and emphasizes two distinct mode of regional extension for the Palaeozoic (Neotethys opening) and Mesozoic (abyssal plains opening). The structural workflow is used for the definition of the structural evolution of the Laminaria High area (Bonaparte Basin). Following a regional structural characterization of the Timor Sea (chapter 4.1), a thorough analysis of the Mesozoic fault architecture reveals a local rotation of the stress field and the development of reverse structures (flower structures) in extensional setting, that form potential hydrocarbon traps (chapter 4.2). The definition of the complex Neogene structural architecture associated with the fault kinematic analysis and a plate flexure model (chapter 4.3) suggest that the Miocene to Pleistocene reactivation phases recorded at the Laminaria High most probably result from the oblique normal reactivation of the underlying Mesozoic fault planes. This episode is associated with the deformation of the subducting Australian plate. Based on these results three papers were published in international journals and two additional publications will be submitted. Additionally this research led to several communications in international conferences. Although the different workflows presented in this research have been primarily developed and used for the analysis of specific stratigraphic and structural geobodies on the Australian North West Shelf, similar integrated 3D seismic approaches will have applications to hydrocarbon exploration and production phases; for instance increasing the recognition of potential source rocks, secondary migration pathways, additional traps or reservoir breaching mechanisms. The new elements brought by this research further highlight that 3D seismic data contains a tremendous amount of hidden geological information waiting to be revealed and that will undoubtedly bring new insight into depositional systems, structural evolution and geohistory of the areas reputed being explored and constrained and other yet to be constrained. The further development of 3D texture attributes highlighting specific features of the seismic signal, the integration of quantitative analysis for stratigraphic and structural processes, the automation of the interpretation workflow as well as the formal definition of "seismo-morphologic" characteristics of a wide range of geobodies from various environments would represent challenging examples of continuation of this present research. The 21st century will most probably represent a transition period between fossil and other alternative energies. The next generation of seismic interpreters prospecting for hydrocarbon will undoubtedly face new challenges mostly due to the shortage of obvious and easy targets. They will probably have to keep on integrating techniques and geological processes in order to further capitalise the seismic data for new potentials definition. Imagination and creativity will most certainly be among the most important quality required from such geoscientists.

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The arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the currently known sequences of arenavirus GPCs revealed the presence of a highly conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side in Old World and clade C New World arenaviruses but not in New World viruses of clades A and B or cellular substrates of SKI-1/S1P. Using a combination of molecular modeling and structure-function analysis, we found that residueY285 of SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular recognition of the aromatic "signature residue" at P7 in the GPC of Old World Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI-1/S1P is crucial for the efficient processing of peptides derived from Old World and clade C New World arenavirus GPCs but not of those from clade A and B New World arenavirus GPCs. The data suggest that during coevolution with their mammalian hosts, GPCs of Old World and clade C New World viruses expanded the molecular contacts with SKI-1/S1P beyond the classical four-amino-acid recognition sequences and currently occupy an extended binding pocket.

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OBJECTIVES: To identify factors associated with discrepant outcome reporting in randomized drug trials. STUDY DESIGN AND SETTING: Cohort study of protocols submitted to a Swiss ethics committee 1988-1998: 227 protocols and amendments were compared with 333 matching articles published during 1990-2008. Discrepant reporting was defined as addition, omission, or reclassification of outcomes. RESULTS: Overall, 870 of 2,966 unique outcomes were reported discrepantly (29.3%). Among protocol-defined primary outcomes, 6.9% were not reported (19 of 274), whereas 10.4% of reported outcomes (30 of 288) were not defined in the protocol. Corresponding percentages for secondary outcomes were 19.0% (284 of 1,495) and 14.1% (334 of 2,375). Discrepant reporting was more likely if P values were <0.05 compared with P ≥ 0.05 [adjusted odds ratio (aOR): 1.38; 95% confidence interval (CI): 1.07, 1.78], more likely for efficacy compared with harm outcomes (aOR: 2.99; 95% CI: 2.08, 4.30) and more likely for composite than for single outcomes (aOR: 1.48; 95% CI: 1.00, 2.20). Cardiology (aOR: 2.34; 95% CI: 1.44, 3.79) and infectious diseases (aOR: 1.77; 95% CI: 1.01, 3.13) had more discrepancies compared with all specialties combined. CONCLUSION: Discrepant reporting was associated with statistical significance of results, type of outcome, and specialty area. Trial protocols should be made freely available, and the publications should describe and justify any changes made to protocol-defined outcomes.

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While the influence of HLA-AB and -DRB1 matching on the outcome of bone marrow transplantation (BMT) with unrelated donors is clear, the evaluation of HLA-C has been hampered by its poor serological definition. Because the low resolution of standard HLA-C typing could explain the significant number of positive cytotoxic T lymphocyte precursor frequency (CTLpf) tests found among HLA-AB-subtype, DRB1/B3/B5-subtype matched patient/donor pairs, we have identified by sequencing the incompatibilities recognized by CD8+ CTL clones obtained from such positive CTLpf tests. In most cases the target molecules were HLA-C antigens that had escaped detection by serology (e.g. Cw*1601, 1502 or 0702). Direct recognition of HLA-C by a CTL clone was demonstrated by lysis of the HLA class I-negative 721.221 cell line transfected with Cw*1601 cDNA. Because of the functional importance of Cw polymorphism, a PCR-SSO oligotyping procedure was set up allowing the resolution of 29 Cw alleles. Oligotyping of a panel of 382 individuals (including 101 patients and their 272 potential unrelated donors, 5 related donors and 4 platelet donors) allowed to determine HLA-C and HLA A-B-Cw-DRB1 allelic frequencies, as well as a number of A-Cw, B-Cw, and DRB1-Cw associations. Two new HLA-Cw alleles (Cw*02023 and Cw*0707) were identified by DNA sequencing of PCR-amplified exon 2-intron 2-exon 3 amplicons. Furthermore, we determined the degree of HLA-C compatibility in 287 matched pairs that could be formed from 73 patients and their 184 potential unrelated donors compatible for HLA-AB by serology and for HLA-DRB1/ B3/B5 by oligotyping. Cw mismatches were identified in 42.1% of these pairs, and AB-subtype oligotyping showed that 30% of these Cw-incompatible pairs were also mismatched for A or B-locus subtype. The degree of HLA-C incompatibility was strongly influenced by the linkage with B alleles and by the ABDR haplotypes. Cw alleles linked with B*4403, B*5101, B18, and B62 haplotypes were frequently mismatched. Apparently high resolution DNA typing for HLA-AB does not result in full matching at locus C. Since HLA-C polymorphism is recognized by alloreactive CTLs, such incompatibilities might be as relevant as AB-subtype mismatches in clinical transplantation.

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Since the mid 20th century progress in biomedical science has been punctuated by the emergence of bioethics which has fashioned the moral framework of its application to both research and clinical practice. Can we, however, consider the advent of bioethics as a form of progress marking the advances made in biomedical science with an adequate ethical stamp? The argument put forward in this chapter is based on the observation that, far from being a mark of progess, the development of bioethics runs the risk of favouring, like modern science, a dissolution of the links that unite ethics and medicine, and so of depriving the latter of the humanist dimensions that underlie the responsibilities that fall to it. Faced with this possible pitfall, this contribution proposes to envisage as a figure of moral progress, consubstantial with the development of biomedical science, an ethical approach conceived as a means of social intervention which takes the first steps towards an ethics of responsibility integrating the bioethical perspective within a hermeneutic and deliberative approach. By the yardstick of a prudential approach, it would pay particular attention to the diverse sources of normativity in medical acts. It is suggested that this ethical approach is a source of progress insofar as it constitutes an indispensable attitude of watchfulness, which biomedical science can lean on as it advances, with a view to ensuring that the fundamental link uniting ethics and medicine is maintained.

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This paper examines three specific issues raised by The Ethical Project. First, I discuss the varieties of altruism and spell out the differences between the definitions proposed by Kitcher and the ways altruism is usually conceived in biology, philosophy, psychology, and economics literature. Second, with the example of Kitcher's account, I take a critical look at evolutionary stories of the emergence of human ethical practices. Third, I point to the revolutionary implications of the Darwinian methodology when it is thoughtfully applied to ethics.

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In unicolonial populations of ants, individuals can mix freely within large networks of nests that contain many queens. It has been proposed that the absence of aggression in unicolonial populations stems from a loss of nest mate recognition, but few studies have tested this hypothesis. We investigated patterns of aggression and nest mate recognition in the unicolonial wood ant, Formica paralugubris. Little aggression occurred, even between workers from nests separated by up to 5 km. However, when aggression took place, it was directed toward non-nest mates rather than nest mates. Trophallaxis (exchange of liquid food) occurred very frequently, and surprisingly, workers performed significantly more trophallaxis with non-nest mates than with nest mates (bias 2.4:1). Hence, workers are able to discriminate nest mates from non-nest mates. Higher rates of trophallaxis between non-nest mates may serve to homogenize the colony odor or may be an appeasement mechanism. Trophallaxis rate and aggression level were not correlated with geographical distance and did not differ within and between two populations separated by several kilometers. Hence, these populations do not represent differentiated supercolonies with clear-cut behavioral boundaries. Overall, the data demonstrate that unicoloniality can evolve despite well-developed nest mate recognition. Reduced levels of aggression might have been favored by the low rate of interactions with foreign workers, high cost of erroneously rejecting nest mates, and low cost of accepting foreign workers.

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Introduction: Difficult tracheal intubation remains a constant and significant source of morbidity and mortality in anaesthetic practice. Insufficient airway assessment in the preoperative period continues to be a major cause of unanticipated difficult intubation. Although many risk factors have already been identified, preoperative airway evaluation is not always regarded as a standard procedure and the respective weight of each risk factor remains unclear. Moreover the predictive scores available are not sensitive, moderately specific and often operator-dependant. In order to improve the preoperative detection of patients at risk for difficult intubation, we developed a system for automated and objective evaluation of morphologic criteria of the face and neck using video recordings and advanced techniques borrowed from face recognition. Method and results: Frontal video sequences were recorded in 5 healthy volunteers. During the video recording, subjects were requested to perform maximal flexion-extension of the neck and to open wide the mouth with tongue pulled out. A robust and real-time face tracking system was then applied, allowing to automatically identify and map a grid of 55 control points on the face, which were tracked during head motion. These points located important features of the face, such as the eyebrows, the nose, the contours of the eyes and mouth, and the external contours, including the chin. Moreover, based on this face tracking, the orientation of the head could also be estimated at each frame of the video sequence. Thus, we could infer for each frame the pitch angle of the head pose (related to the vertical rotation of the head) and obtain the degree of head extension. Morphological criteria used in the most frequent cited predictive scores were also extracted, such as mouth opening, degree of visibility of the uvula or thyreo-mental distance. Discussion and conclusion: Preliminary results suggest the high feasibility of the technique. The next step will be the application of the same automated and objective evaluation to patients who will undergo tracheal intubation. The difficulties related to intubation will be then correlated to the biometric characteristics of the patients. The objective in mind is to analyze the biometrics data with artificial intelligence algorithms to build a highly sensitive and specific predictive test.

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Using the lens of positive organizational ethics, we theorized that empathy affects decisions in ethical dilemmas that concern the well-being of not only the organization but also other stakeholders. We hypothesized and found that empathetic managers were less likely to comply with requests by an authority figure to cut the wages of their employees than were non-empathetic managers. However, when an authority figure requested to hold wages constant, empathy did not affect wage cut decisions. These findings imply that empathy can serve as a safeguard for ethical decision making in organizations during trying times without generally undermining organizational effectiveness. We conclude by discussing the implications of our research.

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1. Identifying the boundary of a species' niche from observational and environmental data is a common problem in ecology and conservation biology and a variety of techniques have been developed or applied to model niches and predict distributions. Here, we examine the performance of some pattern-recognition methods as ecological niche models (ENMs). Particularly, one-class pattern recognition is a flexible and seldom used methodology for modelling ecological niches and distributions from presence-only data. The development of one-class methods that perform comparably to two-class methods (for presence/absence data) would remove modelling decisions about sampling pseudo-absences or background data points when absence points are unavailable. 2. We studied nine methods for one-class classification and seven methods for two-class classification (five common to both), all primarily used in pattern recognition and therefore not common in species distribution and ecological niche modelling, across a set of 106 mountain plant species for which presence-absence data was available. We assessed accuracy using standard metrics and compared trade-offs in omission and commission errors between classification groups as well as effects of prevalence and spatial autocorrelation on accuracy. 3. One-class models fit to presence-only data were comparable to two-class models fit to presence-absence data when performance was evaluated with a measure weighting omission and commission errors equally. One-class models were superior for reducing omission errors (i.e. yielding higher sensitivity), and two-classes models were superior for reducing commission errors (i.e. yielding higher specificity). For these methods, spatial autocorrelation was only influential when prevalence was low. 4. These results differ from previous efforts to evaluate alternative modelling approaches to build ENM and are particularly noteworthy because data are from exhaustively sampled populations minimizing false absence records. Accurate, transferable models of species' ecological niches and distributions are needed to advance ecological research and are crucial for effective environmental planning and conservation; the pattern-recognition approaches studied here show good potential for future modelling studies. This study also provides an introduction to promising methods for ecological modelling inherited from the pattern-recognition discipline.

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Naturally acquired immune responses against human cancers often include CD8(+) T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1(157-165)-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with alpha-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1(157-165) peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of alphabeta TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.