182 research outputs found
Bayesian methods for addressing long-standing problems in associative learning: The case of PREE
No full textThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Joaquin Moris was funded with a Juan de la Cierva Postdoctoral grant. This research was supported by grants PSI2013-43516-R and PSI2016-78818-R of the Spanish Ministry of Economy and Competitiveness, and grant IT955-16 of the Basque Government
Defining the translatome of HIV-1 to identify novel conserved T-cell antigens
No full textLes récentes avancées dans les méthodes de détection ont remis en question la définition traditionnelle du génome codant en révélant que des milliers de cadres ouverts de lecture non canoniques, tels que les cadres de lecture alternatifs (ARFs), sont capables de coder des polypeptides. Bien que les ARFs aient été identifiés dans plusieurs génomes viraux grâce à la technique du ribosome profiling, tels que ceux du HCMV, KSV et SARS-CoV-2, aucune démonstration n'avait pas été faite sur le génome du VIH-1. En utilisant le ribosome profiling, nous avons identifié 98 ARFs du VIH-1 répartis sur l'ensemble du génome, avec une forte conservation parmi les isolats des clades B et C du VIH-1. Notre étude a révélé qu'au moins 42 ARFs codent des polypeptides viraux, ce qui est attesté par la détection de réponses T spécifiques de 46 peptides dérivés d'ARFs chez les donneurs sous traitement ou contrôlant naturellement l'infection.Parallèlement, nous avons identifié dans des cellules primaires infectées un ligand de HLA-A*0201 dérivé d'un ARF identifié. Les réponses T spécifiques des peptides dérivés d'ARFs étaient majoritairement médiées par des cellules T CD4+ polyfonctionnelles sécrétant au moins 3 cytokines simultanément. Notre étude met en évidence l'immense capacité de codage du VIH-1 et l'intérêt d'étudier la traduction des régions génomiques non canoniques dans les maladies infectieuses. Notre découverte élargit la liste des polypeptides viraux conservés qui pourraient être des cibles potentielles pour les stratégies de vaccination.Recent advances in detection methods challenged the coding definition revealing that thousands of non-canonical open reading frames, including alternative reading frames (ARFs), encode polypeptides. ARFs have been detected in several viral genomes using ribosome profiling such as HCMV, KSV, and SARS-CoV-2 but no demonstration has been made on HIV-1 genome. By utilizing ribosome profiling, we uncovered 98 HIV ARFs that are distributed throughout the genome, and highly conserved among HIV clades B and C isolates. Our analysis revealed that at least 42 ARFs encode viral polypeptides, as demonstrated by T-cell responses targeting 46 ARF-derived peptides in donors under treatment or naturally controlling the infection.At the same time, we identified a ligand of HLA-A*0201 derived from an identified ARF on primary infected cells. The ARF-specific T-cell responses were mediated by polyfunctional CD4+ T-cells secreting at least 3 cytokines simultaneously. Our study highlights the immense translation landscape of HIV genome and the interest to study hidden alternative translated genomic regions in infectious diseases. Our discovery expands the list of conserved viral polypeptides that might be potential targets for vaccination strategies
Clinical Actionability of the Genomic Landscape of Metastatic Castration Resistant Prostate Cancer
No full textThe development of targeted therapies increases treatment options for metastatic castration resistant prostate cancer (mCRPC) patients. There is a need for strong predictive and prognostic signatures to guide physicians in treating mCRPC patients. In this review we unravel the possible actionability in the AR pathway, PI3K AKT signaling, and DNA repair pathways. Additionally, we make recommendations on biomarker trial design, and the clinical use of this new type of data.sponsorship: This research received no external funding. This research was supported by the 'Jozef De Wever' fund for prostate cancer prevention of the KU Leuven, Leuven, Belgium. ('Jozef De Wever' fund for prostate cancer prevention of the KU Leuven, Leuven, Belgium)status: Publishe
Prostate cancer: The influence of steroid metabolism on CYP17A1 inhibitor activity
No full textGaleterone is a steroid 17‑α‑hydroxylase/17,20 lyase and androgen receptor antagonist intended for patients with prostate cancer. Similar to abiraterone, galeterone has a steroid scaffold structure and mimics natural ligands; thus, these agents are metabolized by the same enzymes that synthesize or degrade naturally occurring steroids, which can result in attenuated efficacy.status: Publishe
Teachers must reclaim their authority in age of AI
No full textThis article reflects on the evolving challenges faced by educators in the age of generative artificial intelligence (AI). Drawing from semester-long observations, the author highlights how AI has altered students’ approaches to academic tasks, often resulting in overreliance, weakened critical engagement, and blurred authorship. While acknowledging AI’s benefits in efficiency and idea generation, the article argues that its integration into education requires thoughtful ethical frameworks and a renewed emphasis on Natural Intelligence (NI)—critical reasoning, moral discernment, and spiritual consciousness. The author contends that teachers must reclaim their authoritative role as mentors and moral guides, ensuring that human wisdom anchors learning processes amid rapid technological change. Ultimately, the article calls for collaborative efforts among educators, curriculum designers, and policymakers to develop balanced, responsible, and human-centred pedagogical practices in an AI-driven world
Tumor Volume and Clinical Failure in High‐Risk Prostate Cancer Patients Treated With Radical Prostatectomy
No full textTo identify the most significant cut-off of tumor volume (TV) for prediction of clinical failure (CF) among high-risk prostate cancer (hPCa) patients.status: Publishe
Effect of viscosity on the cetane number of a diesel fuel
No full textThe object of this paper is to determine or rather experimentally establish the effect of a change in viscosity of a given diesel oil in regard to the ignition quality (cetane rating) of the oil.
The author did not attempt to prove why or find out how much the cetane number was affected. But, merely, tried to experimentally verify the fact that the cetane number of the fuel used underwent a change when its viscosity was decreased by preheating it.
Since his professional interests lie in the field of automotive engineering, several thesis problems were suggested to him by Dr. A. J. Miles, Chairman of the Mechanical Engineering Department, all to be investigated on the C.F.R. gasoline and diesel test engines. Originally “sensitivity” was taken as a thesis problem, for it was a fairly new subject not explored intensively. But later the facilities in the laboratory and the fact that diesel research is still a wide open field led the author to carry his experiments on the C.F.R. diesel testing engine. The author\u27s original idea was to investigate a diesel fuel in regard to a simulation of “sensitivity” as established for the octane numbers of gasolines. He chose, as a first step in doing so, to investigate the relation the fuel viscosity would have on the cetane rating.
Up to 1930 not much research work had been carried out on diesel engines and especially on diesel fuel oils. The following decade, since the tendency toward increasing the speeds of diesel engines had caused them to become more sensitive to fuels and research on the latter had brought out the importance of ignition quality, research work was carried out to standardize a method of test by which diesel fuels could be rated. The importance of ignition quality and viscosity was first recognized by Mr. H. R. Ricardo and attempt in research in this respect was stressed by him --Introduction, pages 1-2
Financial benchmarking
No full textThis bachelor thesis is focused on the financial benchmarking of the company MORIS Design s.r.o. The target is to examine financial situation of the company and to compare the company to the other enterprises in the sector in which it operates. To achieve this, author uses the financial analysis INFA. The first part of this paper is focused on the financial analysis as such in theory. The second part closely examines economic situation of the company MORIS Design s.r.o. and performs its financial benchmarking. Finally, in the third section, there is a conclusion of the financial situation of the company, its strengths and weaknesses and also suggestions that would help it to solve the problems found in the analysis
Rapid Situation Analysis: a hybrid, multi-methods, qualitative, participatory approach to researching tourism development phenomena
No full textThis study develops a hybrid, bottom-up approach to field research, namely Rapid
Situation Analysis, and implements it in Ghana. It draws on elements from two existing
participatory methodological approaches: Rapid Rural Appraisal and Participatory
RuralAppraisal. The approachwas developed to suit the particular needs of investigating
corporate social responsibility practices, sustainable development and poverty reduction
through tourism, a fragmented sector which tends to be ambiguous and unstructured and
lack cohesion (unlike, for example, agriculture or primary health care, both of which
are familiar territory for Rapid Rural Appraisal and Participatory Rural Appraisal). The
Rapid Situation Analysis bottom-up approach to data gathering was underpinned by
supporting methods, including participant and direct observation, in-depth interviews,
stakeholder focus groups and informal conversations. Moreover, the multiple methods
were further enriched by the collection of visual data in the form of moving and still
images. These research findings were fed back to the communities at the centre of the
research
Real-world Evidence on Baseline Characteristics and Treatment in Metastatic Hormone-sensitive Prostate Cancer : Findings from the PIONEER 2.0 Big Data Investigation Group
No full textPIONEER Consortium collaborator list: Laurent Antoni, Charles Auffray, Anssi Auvinen, Chris Bangma, Anders Bjartell, Gabi Bernstein, Angelika Borkowetz, Danny Burke, Michael Bussmann, John Butler, Riccardo Campi, Simona Caputova, Laurence Colette, Louise Fullwood, Ronald Herrera, Thomas Hofmarcher, Marc Holtorf, Denis Horgan, Henkjan Huisman, Tim Hulsen, Andreas Josefsson, Daniel Kotik, Mark Lambrecht, Doron Lancet, Michael Lardas, Ailbhe Lawlor, Stephane Lejeune, Sophia Le Mare, Muriel Licour, Peter Lindgren, Elaine Longden-Chapman, Monika Maass, Maxim Moinat, Lisa Moris, Nicolas Mottet, Teemu Murtola, Kishore Papineni, Sarah Payne, Christian Reich, Kristin Reiche, Maria J. Ribal, Paul Robinson, Monique J. Roobol, Beth Russell, Vasileios Sakalis, Jack Schalken, Sarah Seager, Robert Shepherd, Aino Siltari, Emma Jane Smith, Azadeh Tafreshiha, Kirsi Talala, Teuvo Tammela, Derya Tilki, Patrizia Torremante, Sheela Tripathee, Kees van Bochove, Mieke Van Hemelrijck, Tapio Visakorpi, Marc Dietrich Voss, Jihong Zong, and Nazanin Zounemat Kermani.Peer reviewe
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