Reflexiones sobre la decisión de internamiento en campamentos de la Corte Suprema de Kenia

Los grupos de la sociedad civil han acogido una reciente victoria ante la Corte Suprema de Kenia como un recordatorio del importante papel que el litigio estratégico puede desempeñar en la aplicación y promoción de los derechos de los refugiados

Risk factors for bit-related lesions in Finnish trotting horses

Background Bit-related lesions in competition horses have been documented, but little evidence exists concerning their potential risk factors. Objectives To explore potential risk factors for oral lesions in Finnish trotters. Study design Cross-sectional study. Methods The rostral part of the mouth of 261 horses (151 Standardbreds, 78 Finnhorses and 32 ponies) was examined after a harness race. Information on bit type, equipment and race performance was collected. Results A multivariable logistic regression model of Standardbreds and Finnhorses showed a higher risk of moderate or severe oral lesion status associated with horses wearing a Crescendo bit (n = 38, OR 3.6, CI 1.4–8.9), a mullen mouth regulator bit (n = 25, OR 9.9, CI 2.2-45) or a straight plastic bit (n = 14, OR 13.7, CI 1.75-110) compared with horses wearing a snaffle trotting bit (n = 98, P = .002). Bar lesions (67 horses) were more common in horses wearing unjointed bits than in horses wearing jointed bits (Fisher's exact test P < .001). Lesions in the buccal area and the inner lip commissures were not associated with bit type. Using a tongue-tie or an overcheck, galloping, placement in the top three or money earned in the race were not associated with lesion risk. Main limitations The sample size for certain bit types was insufficient for statistical analysis. Conclusions Moderate and severe oral lesion status was more common in horses wearing a Crescendo bit, a mullen mouth regulator bit or a straight plastic bit than in horses wearing a single-jointed snaffle trotting bit. However, lesions were observed regardless of bit type. Further studies on rein tension, the interaction between bit type and rein tension and prevention of mouth lesions in trotters are warranted.Peer reviewe

Structural magnetic resonance imaging in amyotrophic lateral sclerosis: cortical morphometry, diffusion properties and lesion detection as potential biomarkers for the state and progression of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the motor system of the central nervous system. The aim of this thesis is to evaluate the potential of structural magnetic resonance imaging (MRI) biomarkers of the brain grey matter (GM) and white matter (WM) for the state and progression of ALS. The thesis has been conducted on behalf of a treatment program on a named patient basis at the University Hospital of Regensburg. 31 patients with written informed consent are compared to a control sample of 34 age-matched healthy participants. Routine MRI scans have been conducted approximately every 3 months and include T1-weighted imaging, diffusion weighted imaging (DWI), and fluid-attenuated inversion recovery (FLAIR) sequences at 1.5 Tesla. The subprojects of the thesis investigate precentral and postcentral cortical thinning (study 1), spread of alterations of fractional anisotropy (FA) across different WM types (study 2), and FLAIR lesion detection (study 3) in the same ALS cohort. Candidate MRI biomarkers are associated with neurophysiological and clinical biomarkers. Statistical analysis includes both cross-sectional and longitudinal analyses. Special focus is set on the individual patient. Cortical thinning is more pronounced in the precentral cortex than in the postcentral cortex. Combinatory biomarker use reveals evident differences in temporal dynamics of cortical thickness, clinical and neurophysiological biomarkers over time. Reduction of FA is consistently detected in the corticospinal tract (CST) and extra motor WM and most pronounced in the brainstem. Spread of FA alterations resembles both dying-forward and dying-back disease propagation and is not linked to patients’ clinical or demographic characteristics. WM lesions as detected by FLAIR hyperintensity are more frequent in ALS patients than in controls, most pronounced in the CST, and associated with an inferior survival. Together, the findings of this thesis suggest that MRI biomarkers may contribute to the diagnosis, prognosis and understanding of ALS disease and disease courses on an individual scope

Interferometry in an Atomic Fountain with Ytterbium Bose-Einstein Condensates

We present enabling experimental tools and atom interferometer implementations in a vertical "fountain" geometry with ytterbium Bose-Einstein condensates. To meet the unique challenge of the heavy, non-magnetic atom, we apply a shaped optical potential to balance against gravity following evaporative cooling and demonstrate a double Mach-Zehnder interferometer suitable for applications such as gravity gradient measurements. Furthermore, we also investigate the use of a pulsed optical potential to act as a matter wave lens in the vertical direction during expansion of the Bose-Einstein condensate. This method is shown to be even more effective and results in a reduction of velocity spread (or equivalently an increase in source brightness) of more than a factor of five, which we demonstrate using a two-pulse momentum-space Ramsey interferometer. The vertical geometry implementation of our diffraction beams ensures that the atomic center of mass maintains overlap with the pulsed atom optical elements, thus allowing extension of atom interferometer times beyond what is possible in a horizontal geometry. Our results thus provide useful tools for enhancing the precision of atom interferometry with ultracold ytterbium atoms.Comment: 11 pages, 7 figure

Meet Bob and Offset Your Flight: Optimising Explainer Videos to Promote Voluntary Carbon Offsetting

In Germany, over 60% of people use YouTube as a search engine and watch explainer videos or tutorials at least occasionally. Two studies were conducted to determine how explainer videos can be optimised to promote sustainable minority behaviour such as voluntary carbon offsetting. A typical way to present information in explainer videos is by using exemplars (the “meet Bob” trope), which can change recipients’ judgements of the frequency of events. When an exemplar is included, the frequency of occurrence can be estimated to be higher, even if the actual base-rate information is given. Therefore, study one (N = 482) tested whether an exemplar could enhance the positive effects of a dynamic descriptive social norm appeal (DSNA), prevent the backfire effects of a static minority DSNA, and examine whether there were any differences depending on the narrative perspective. In study one, we conducted a 2 (narrative perspective: first vs. third person) × 2 (DSNA: static vs. dynamic) × 2 (travel destination: Europe vs. overseas; control factor) between-subjects experiment using six self-produced explainer videos about voluntary carbon offsetting (N = 270). The results show that the narrative perspective, different DSNAs, and the destination had no effect on persuasive outcomes. Study two (N = 270) focused on social norm appeals and supplemented minority DSNAs (DSNA: static vs. dynamic vs. absent) with an injunctive social norm appeal (ISNA: present vs. absent). The results show that a majority injunctive social norm appeal can improve attitudes towards voluntary carbon offsetting and perceived effectiveness

Protein folding in living cells and under pressure

Protein folding, the process through which proteins gain their functional structure, can be approached from the perspective of many disciplines. Starting with biology, we can probe how protein structure relates to function and consider how the fold of a protein interacts with the biological environment. From the chemical perspective, we can treat protein folding as a chemical reaction and study the thermodynamics and kinetics of the structural transition. With physics, we can understand the underlying forces that give rise to protein folding and use theory and simulation to describe the protein folding process on an atomic level. This thesis studies protein folding through the lens of all three of these fields with two interdisciplinary methodological themes: one at the interface of chemistry and physics and the other at the interface of biology and chemistry. In section 1, we study in detail the kinetics of fast-folding reactions following pressure-jump perturbation and pair experiment with molecular dynamics simulations. The first chapter is a review of the effects of pressure on the structure of biomolecules as well as a brief literature review of pressure-probed protein folding kinetics. We see that the methodology to study pressure-jumps is generally limited by time-scale—very fast folding is hard to study by pressure—and chapter two presents an overview of a fast pressure-jump instrument that meets this challenge. Although this instrument was developed by the previous generation of graduate students, several significant improvements are summarized in the chapter with a detailed user manual for the instrumentation. Closing up the section, we use the fast pressure-jump instrumentation as well as temperature-jump instrumentation to study the microsecond pressure and temperature-jump refolding kinetics of the engineered WW domain FiP35, a model system for beta sheet folding. With a full complement of molecular dynamics experiments mimicking experimental conditions, we show that simulation and experiment are consistent with a four-state kinetic mechanism and highlight FiP35’s position at the boundary where activated intermediates and downhill folding meet. Section 2 focuses on the interface of biology and chemistry, where we study how the protein folding reaction is impacted by immersion in the crowded intracellular environment and explore whether perturbations to the intracellular folding landscape can be linked to protein function. A review of the forces at play in the intracellular environment and the role that ultra-weak “quinary” interactions play inside living cells is presented in chapter 4, which also includes a review of the most recent literature studying biomolecular dynamics in their native environments. In chapter 5 we study the time-dependence of protein folding inside living cells as probed by live-cell fluorescent microscopy. We find that both the rate of folding and the thermodynamic stability of yeast phosphoglycerate kinase (PGK-FRET) are cell cycle-dependent, a process strictly regulated in time, suggesting that the interplay between the intracellular environment and proteins may impact their function. In chapter 6, a new probe to study protein folding in the cell is explored, namely the GFP/ReAsH Forster resonance energy transfer (FRET) pair. We show that this FRET pair suffers from bleaching artifacts but that directly excited ReAsH is an appealing prospect for studying protein folding in living cells on fast and slow time-scales. Finally, chapter 7 builds on the work presented in chapter 5 and chapter 6 by seeking a protein candidate whose function and in cell folding dynamics are linked. Several constructs of p53, a transcription factor, are explored as potential candidates for answering the question of whether protein activity level indeed can correlate with stability in living cells

Enabling Open Science in Medicine Through Data Sharing: An Overview and Assessment of Common Approaches from the European Perspective

Open Science involves the sharing of knowledge and data as well as the exchange of research results. This is particularly important in the biomedical field, as it can foster validation studies in response to the replication crisis and improve resource utilisation. Since medical data is particularly privacy sensitive, its processing is subject to strong data protection requirements. Agencies, institutions, and projects in the European Union are still struggling with the establishment of widely accepted mechanisms supporting the sharing of data for Open Science practices. The goal of this paper is to provide an overview of different methods that have been used for this purpose and to discuss their technical properties and legal challenges. Our assessment is based on well-known conceptualizations, such as the Five Safes Framework. The result shows that different approaches provide different trade-offs between the functionalities and the degree of data protection provided, and that there are open legal issues. Current legislative initiatives in the EU, including regulations for the European Health Data Space and the Data Governance Act, have the potential to address some of the resulting uncertainties

'Getting the VIBE’ in biochemistry education

Adapting to the recent changing educational landscape has inevitably widened the knowledge gap within an undergraduate biochemistry cohort, presenting challenges to educators to engage with and enhance understanding in biochemistry.  Students with a tenuous grasp of basic chemistry (and mathematics) concepts struggle to progress.  Visual literacy requires interpreting external representations of molecules into a spatial, 3D conceptual understanding yet competency can be hard to achieve (Linenberger et al, 2015; Hall, 2017; Lohning, 2019).  This study aimed to enhance engagement and understanding by incorporating a series of voluntary workshops harnessing 3D technologies focused on identifying key protein-ligand interactions underpinning drug action. Our ‘VIBE’ (or ‘Virtual reality In Biochemistry Education’) sessions included use of Oculus headsets (VR) allowing students to ‘step inside a protein’, molecular modelling (cheminformatics) and 3D printed proteins. During the session, students completed a workbook prior to being invited to participate in a qualitative feedback survey on their experience, perceived learning and engagement. Qualitative data were analysed thematically while quantitative data comparing students’ preferences and perceptions were represented graphically as percentage of participant pool. 80-100% of participants, between 2020-2023, agreed both VR and 3D modelling improved understanding because of the ability to physically explore structure at the molecular level detail while VR lead improved engagement. Thematic analysis supported enhanced engagement with VR and virtual, 3D modelling platforms. 3D printed proteins were less useful due to print quality limitations. Cost and technical considerations for these sessions were not trivial and are limited to small groups. This valuable feedback will help guide deployment of 3D technologies for future cohorts. REFERENCES Linenberger, K. J., &amp; Bretz, S. L. (2015). Biochemistry students' ideas about how an enzyme interacts with a substrate. Biochemistry and molecular biology education: a bimonthly publication of the International Union of Biochemistry and Molecular Biology, 43(4), 213–222. https://doi.org/10.1002/bmb.20868 Hall, S., Grant, G., Arora, D., Karaksha, A., McFarland, A., Lohning, A., &amp; Anoopkumar-Dukie, S. (2017). A pilot study assessing the value of 3D printed molecular modelling tools for pharmacy student education. Currents in Pharmacy Teaching &amp; Learning, 9(4), 723–728. https://doi.org/10.1016/j.cptl.2017.03.029 Lohning, A. E., Hall, S., &amp; Dukie, S. (2019). Enhancing Understanding in Biochemistry Using 3D Printing and Cheminformatics Technologies: A Student Perspective. Journal of Chemical Education, 96(11), 2497-2502. https://doi.org/10.1021/acs.jchemed.8b0096