Pragmatic Epistemic Justification and F. Gonseth"s Idoneism

What is knowledge ? How can knowledge be distinguished from simple opinion or belief ? Are we able to insure ourselves against error ? This is the kind of questions that Socrates asks the young Theaitetes. During the dialogue, several successive definitions are proposed, the last one being that knowledge is true belief followed by its justification

Identification and biological validation of HPV16 E6/E7-derived T cell target epitopes and their use for performance assessment of MHC class I binding predictors

Persistent infection with high-risk types of human papillomavirus (HPV) can cause several malignancies, in particular oropharyngeal and anogenital cancers. HPV16 has been identified as the most prevalent high-risk type, being related to 60% of cervical cancers, 75% of oropharyngeal cancers, 71% of anal cancers and the majority of precancerous lesions. As standard of care treatment is invasive, and harbors risks and side effects, there is a need for new approaches. For rationally designing a therapeutic vaccine against HPV-induced malignancies, it is essential to identify suitable target epitopes, which are presented on the surface of an HPV-transformed cell and induce immune responses that eventually mediate target cell death. The HPV16 oncoproteins E6 and E7 represent ideal targets for immunotherapy as they mediate the transforming potential of the virus and are constitutively expressed in all malignant cells. In order to define HPV16 target epitopes, in this thesis several algorithms were used to predict potential HPV16 E6- and E7-derived binders of human leukocyte antigen (HLA) class I in silico. Predicted peptides were synthesized and HLA binding capacity was validated in competition-based cellular binding assays. To ensure broad population coverage, predictions and validations were performed for seven frequent HLA alleles: A*01:01, A*02:01, A*03:01, A*11:01, A*24:02, B*07:02 and B*15:01. Including peptides derived from HPV16 E6/E7 variants containing amino acid changes, 271 peptides were experimentally assessed and 69 binders were identified. Combined with previous results, the total HPV16 E6/E7 dataset comprised 779 peptide-HLA measurements. The HPV16 E6/E7 dataset was used to evaluate the performance of employed predictors. No single algorithm was outperforming other methods, but different predictors were found to be best for different settings, depending on investigated HLA type and peptide length. As applying commonly used decision threshold yielded only low sensitivity, criteria for optimal decision thresholds were defined and optimal thresholds were calculated for individual predictors, HLA-types and peptide lengths. Comparing threshold-dependent performance of predictors showed that using criteria-based thresholds allowed more sensitive prediction of HLA-binding peptides without a strong negative influence on prediction accuracy. To identify T cell epitopes among the HPV16 E6- and E7-derived HLA ligands, their capacity to induce immune responses was investigated. To this end, peripheral blood mononuclear cells of healthy donors were HLA-typed and stimulated with respective peptides to generate epitope-specific T cell lines. By assessing interferon-γ-secretion of these T cells, 31 immunogenic peptides were identified. Further characterizing the functionality of epitopes in cytotoxicity assays, five of ten immunogenic HLA-A*02:01-peptides mediated specific killing of HPV16+ target cells by CD8+ T cells. In conclusion, several immunogenic HPV16 E6-and E7-derived epitopes were identified, which are the basis for rational design of a therapeutic HPV vaccine. Additionally, this thesis provides an evaluation of peptide–HLA class-I binding prediction method and recommendations to increase prediction sensitivity to extend the number of potential epitopes as targets for immunotherapy

Concentration and Size Distributions of Nanoparticle Emissions during Low Temperature Combustion using Fuels for Advanced Combustion Engines (FACE)

Due to tightening emission legislations, both within the US and Europe, including concerns regarding greenhouse gases, next-generation combustion strategies for internal combustion (IC) diesel engines that simultaneously reduce exhaust emissions while improving thermal efficiency have drawn increasing attention during recent years. In-cylinder combustion temperature plays a critical role in the formation of pollutants as well as in thermal efficiency of the propulsion system. One way to minimize both soot and NOx emissions, is to limit the in-cylinder temperature during the combustion process by means of high levels of dilution via exhaust gas recirculation (EGR) combined with flexible fuel injection strategies. However, fuel chemistry plays a significant role in the ignition delay; hence, influencing the overall combustion characteristics and the resulting emissions. The Advanced Vehicles, Fuels, and Lubricants (AVFL) committee of the Coordinating Research Council (CRC) specified and formulated a matrix of nine test fuels for advanced combustion engines (FACE) based on the variation of three properties: cetane number, aromatic content, and 90 percent distillation temperature.;The primary objective of this study was to study the effects of various FACE diesel fuels on the nanoparticle formation during low temperature combustion processes. An experimental study was performed at West Virginia University\u27s Engine and Emission Research Laboratory (EERL) to determine the FACE property effects on the low temperature combustion (LTC) process in a turbo-charged GM 1.9L light-duty compression ignition engine under steady-state operating conditions (2100rpm/3.5bar BMEP). A comprehensive test matrix was developed including intake oxygen (O2), as a surrogate for EGR fractions, and rail-pressure parameter variations during single injection timing settings. Furthermore, the influence of varying injection timing and fuel fraction during split injection strategy onto nanoparticles was investigated as well.;Diluted exhaust gas emissions extracted from the CVS tunnel were measured continuously using a Horiba MEXA-7200D gaseous emissions analyzer and included total hydrocarbons (THC), carbon monoxide (CO) as well as carbon dioxide (CO 2) and oxides of nitrogen (NOx). NOx and O 2 concentrations were measured in the raw exhaust and intake manifold using Horiba MEXA-720 NOx analyzers, respectively.;Furthermore, the AVL Micro Soot Sensor, consisting of a measuring unit and an exhaust conditioning unit, was used to measure the soot concentration in the raw exhaust based on the photoacoustic measurement method.;Nanoparticle concentration and size distributions were determined using the Exhaust Emissions Particle Sizer (EEPS(TM)) spectrometer from TSI Inc. (model 3090) as well as the Differential Mobility Spectrometer (DMS) from Cambustion (model DMS500). Continuous exhaust gas samples were extracted from the CVS tunnel (dilution ratio DR ≈ 10) and routed through a double stage dilution system using ejector type dilutors. The first stage was maintained at 140°C (DR ≈ 6) in order to suppress condensation and particle nucleation phenomena, while the second stage utilized dilution air at ambient temperatures (∼25°C, DR ≈ 11).;Particle number concentration increased with a simultaneous increase in particle diameter for both single and split injection strategies in case of FACE diesel fuels with increasing CN for the low NOx, low soot and highest BTE tests. Advancing the start of injection timing led to a decrease in particle number concentration, but a simultaneous increase in nanoparticle emissions was observed for low CN fuels

La contrainte en psychiatrie: actualités et perspectives

La contrainte reste encore fréquemment utilisée en psychiatrie et tend à être considérée comme une nécessité, face à un patient en danger ayant perdu sa capacité de discernement. Cet article vise à rapporter et à discuter l'état actuel des connaissances scientifiques sur ce sujet. Les différentes mesures associées à la contrainte participent avec la maladie au stress vécu par les patients et pourraient compromettre leur adhésion aux offres de soins. La contrainte exercée, le statut légal et la contrainte ressentie sont trois dimensions à intégrer dans notre réflexion. Des pressions symboliquement négatives, positives ou légales sont exercées sur les patients et conduisent à s'interroger sur le développement d'alternatives à l'usage de la contrainte. L'introduction des directives anticipées dans des lois cantonales suisses pourrait ouvrir la voie à des modalités de collaboration différentes et mieux acceptées par les patients. [Auteurs]]]> Coercion ; Psychiatry ; Commitment of Mentally Ill ; Physician-Patient Relations oai:serval.unil.ch:BIB_B5BBAA6ED093 2022-05-07T01:25:32Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_B5BBAA6ED093 Significant reproductive skew in the facultatively polygynous ant Pheidole pallidula info:doi:10.1046/j.1365-294X.2003.02036.x info:eu-repo/semantics/altIdentifier/doi/10.1046/j.1365-294X.2003.02036.x info:eu-repo/semantics/altIdentifier/pmid/14653800 Fournier, D. Aron, S. Keller, L. info:eu-repo/semantics/article article 2004-01 Molecular Ecology, vol. 13, no. 1, pp. 203-10 info:eu-repo/semantics/altIdentifier/pissn/0962-1083 <![CDATA[Reproductive skew - the extent to which reproduction is unevenly shared between individuals in a social group - varies greatly between and within animal species. In this study, we investigated how queens share parentage in polygynous (multiple queen) colonies of the Mediterranean ant Pheidole pallidula. We used highly polymorphic microsatellites markers to determine parentage of gynes (new queens), males and workers in P. pallidula field colonies. The comparison of the genotypes of young and adult workers revealed a very low queen turnover (less than 2%). The first main finding of the study of reproductive skew in these colonies was that there was a significant departure from equal contribution of queens to gyne, male and worker production. Reproductive skew was greater for male production than for queen and worker production. There was no relationship between the magnitude of the reproductive skew and the number of reproductive queens per colony, their relatedness and the overall colony productivity, some of the factors predicted to influence the extent of reproductive skew. Finally, our study revealed for the first time a trade-off in the relative contribution of nestmate queens to gyne and worker production. The queens contributing more to gyne production contributed significantly less to worker production

Non-legislated emissions and PN of two passenger cars with gasoline-butanol blends

Increasing the sustainability of individual transportation and replacing a part of fossil energy in traffic by renewable energy carriers are worldwide important objectives. Bioalcohols are generally recognized as one of very useful alternatives. The global share of bioethanol used for transportation is continuously increasing. Butanol, a four-carbon alcohol, is considered in the last years as an interesting alternative fuel, both for diesel and for gasoline application. Its advantages for engine operation are: good miscibility with gasoline and diesel fuels, higher calorific value than ethanol, lower hygroscopicity, lower corrosivity and possibility of replacing aviation fuels. In the present work, the emissions of two gasoline vehicles – with older and with newer technology – were investigated in dynamic-, stationary and cold start operation

Intensive Case Management for Addiction to promote engagement with care of people with severe mental and substance use disorders: an observational study.

Co-occurring severe mental and substance use disorders are associated with physical, psychological and social complications such as homelessness and unemployment. People with severe mental and substance use disorders are difficult to engage with care. The lack of treatment worsens their health and social conditions and increases treatment costs, as emergency department visits arise. Case management has proved to be effective in promoting engagement with care of people with severe mental and substance use disorders. However, this impact seemed mainly related to the case management model. The Intensive Case Management for Addiction (ICMA) aimed to improve engagement with care of people with severe mental and substance use disorders, insufficiently engaged with standard treatment. This innovative multidisciplinary mobile team programme combined Assertive Community Treatment and Critical Time Intervention methodologies. The aim of the study was to observe the impact of ICMA upon service use, treatment adherence and quality of support networks. Participants' psychosocial and mental functioning, and substance use were also assessed throughout the intervention. The study was observational. Eligible participants were all the people entering the programme during the first year of implementation (April 2014-April 2015). Data were collected through structured questionnaires and medical charts. Assessments were conducted at baseline and at 12 months follow-up or at the end of the programme if completed earlier. McNemar-Bowker's Test, General Linear Model repeated-measures analysis of variance and non-parametric Wilcoxon Signed Rank tests were used for the analysis. A total of 30 participants took part in the study. Results showed a significant reduction in the number of participants visiting the general emergency department compared to baseline. A significantly decreased number of psychiatric emergency department visits was also registered. Moreover, at follow-up participants improved significantly their treatment adherence, clinical status, social functioning, and substance intake and frequency of use. These promising results highlight the efficacy of the ICMA. The intervention improved engagement with care and the psychosocial situation of people with severe mental and substance use disorders, with consequent direct impact on their substance misuse