Ludwig-Maximilians-Universität München
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Profit and loss decomposition in continuous time and approximations
Get PDFFinancial institutions and insurance companies that analyse the evolution and sources of profits and losses often look at risk factors only at discrete reporting dates, ignoring the detailed paths. Continuous-time decompositions avoid this weakness and also make decompositions consistent across different reporting grids. We construct a large class of continuous-time decompositions from a rearranged version of Itô’s formula, and uniquely identify a preferred decomposition from the axioms of exactness, symmetry and normalisation. This unique decomposition turns out to be a stochastic limit of recursive Shapley values, but it suffers from a curse of dimensionality as the number of risk factors increases. We develop an approximation that breaks this curse when the risk factors almost surely have no simultaneous jumps
Algorithmic dissection of optic flow memory in larval zebrafish
Get PDFThe visual stabilization behavior in the larval zebrafish reflects the history of optic flow experienced in the recent past. This integrative process has gained traction in recent years as a simplified, tractable model of working memory and decision-making. Yet its algorithmic bases are poorly understood. In this study, we first demonstrate that only externally generated, but not self-generated, optic flow contributes to future history-dependent stabilization behaviors. This observation suggests that the hysteresis in the stabilization behavior reflects a sensory low-pass filtering process rather than the self-location memory achieved through path integration. Second, through reverse correlation and delay-based paradigms, we reveal multiple timescales involved in the integration of optic flow. With the help of quantitative modeling, we show that the fish becomes more forgetful about the past optic flow in a more dynamic visual environment. Next, with whole-brain, light-sheet calcium imaging, we find optic-flow-selective neurons that exhibit signatures of motor efference copies in various brain regions, mirroring the behavioral findings. Lastly, with two-photon calcium imaging, we show that inferior olive neurons integrate forward and backward flow separately, giving clues about how the multiple timescales of optic flow integration are implemented. Overall, the results here refine our algorithmic and functional understanding of the history dependence of the visual stabilization behaviors in the larval zebrafish, paving the way for deciphering its circuit implementations
Identification and validation of a tear fluid-derived protein biomarker signature in patients with amyotrophic lateral sclerosis
Get PDFThe diagnosis of Amyotrophic Lateral Sclerosis (ALS) remains challenging, particularly in early stages, where characteristic symptoms may be subtle and nonspecific. The development of disease-specific and clinically validated biomarkers is crucial to optimize diagnosis. Here, we explored tear fluid (TF) as a promising ALS biomarker source, given its accessibility, anatomical proximity to the brainstem as an important site of neurodegeneration, and proven discriminative power in other neurodegenerative diseases. Using a discovery approach, we profiled protein abundance in TF of ALS patients (n = 49) and controls (n = 54) via data-independent acquisition mass spectrometry. Biostatistical analysis and machine learning identified differential protein abundance and pathways in ALS, leading to a protein signature. These proteins were validated by Western blot in an independent cohort (ALS n = 51; controls n = 52), and their discriminatory performance was assessed in-silico employing machine learning. 876 proteins were consistently detected in TF, with 106 differentially abundant in ALS. A six-protein signature, including CRYM, PFKL, CAPZA2, ALDH16A1, SERPINC1, and HP, exhibited discriminatory potential. We replicated significant differences of SERPINC1 and HP levels between ALS and controls across the cohorts, and their combination yielded the best in-silico performance. Overall, this investigation of TF proteomics in ALS and controls revealed dysregulated proteins and pathways, highlighting inflammation as a key disease feature, strengthening the potential of TF as a source for biomarker discovery
“The DESCRIBE-ALS-FTD study: a prospective multicenter observational study of the ALS-FTD spectrum”
Get PDFIdentification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study
Get PDFIntroduction
The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need.
Methods
A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature.
Perspective
The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease
"Allacher Porzellan" - Produktionsbedingungen und Produkte eines SS-Betriebs im Spiegel des 21.Jahrhunderts
Get PDFAnfang Januar 1936 beteiligte sich Heinrich Himmler, für die Öffentlichkeit noch nicht ersichtlich, an der Gründung der Porzellanmanufaktur Allach-München, die seither die SS-Sigrune als Markenzeichen führte. Bereits ein Jahr später wurde die Porzellanproduktion in das Dachauer Werk auf dem SS-Gelände in unmittelbarer Nähe zum dortigen Konzentrationslager verlagert, während am Allacher Standort weiterhin Keramik hergestellt wurde.
Vor dem Hintergrund des kriegsbedingten Arbeitskräftemangels wurden ab 1939/40 erstmals Häftlinge des Konzentrationslagers Dachau in der Porzellanproduktion eingesetzt. Trotz der im Vergleich zu anderen im Konzentrationslagersystem verordneten Arbeitskommandos weniger tödlicher Arbeitsbedingungen waren die Häftlinge auch hier stetiger Unterdrückung, Disziplinierungsmaßnahmen und Gefahren wie Krankheit ausgesetzt.
Die SS-Porzellanmanufaktur Allach sollte als Prestigeprojekt der SS und als Medium zur Verbreitung nationalsozialistischer Ideologie fungieren. Neben harmlos anmutenden Tierfiguren, welche als Massenprodukte produziert wurden und der breiten Bevölkerung als Schmuck für das eigene Heim dienen sollten, galten Objekte wie der „SS-Fahnenträger“ als unverkäuflich und waren allein zu Himmlers Verfügung bestimmt.
Die wirtschaftlichen Interessen der SS sowie deren systematische Durchdringung des KZ-Systems sind in der Forschung grundsätzlich gut belegt. Auch die Allacher Porzellanmanufaktur wurde bereits im Kontext verwaltungstechnischer und ökonomischer Strukturen untersucht. Eine systematische Auseinandersetzung mit dem Einsatz von KZ-Häftlingszwangsarbeit im Unternehmen unter Berücksichtigung der Opferperspektive blieb jedoch bislang aus.
Die vorliegende Arbeit untersucht unter dem Titel „Allacher Porzellan“ – Produktionsbedingungen und Produkte eines SS-Betriebs im Spiegel des 21. Jahrhunderts den Einsatz von Häftlingszwangsarbeitern in der SS-Porzellanmanufaktur Allach, die ideologische Dimension der Objekte sowie den heutigen musealen und erinnerungskulturellen Umgang mit diesen Artefakten. Im Fokus stehen Fragen der historischen Kontextualisierung, der Verantwortung musealer Institutionen und Sammlungen sowie der Rolle der Erinnerungsarbeit im Umgang mit NS-belasteten Objekten
SMAS: Structural MRI-based AD Score using Bayesian supervised VAE
Get PDFThis study introduces the Structural MRI-based Alzheimer’s Disease Score (SMAS), a novel index intended to quantify Alzheimer’s Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). The SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DELCODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=−0.83; ADNI: r=−0.62), age (DELCODE: r=0.50; ADNI: r=0.28), hippocampal volume (DELCODE: r=−0.44; ADNI: r=−0.66), and total gray matter volume (DELCODE: r=−0.42; ADNI: r=−0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies indicated that SMAS may be useful for the early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over 36 months, the SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. The relevance map analysis revealed significant morphological changes in key AD-related brain regions, including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex, highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression
Pedigree Painter (pepa): a tool for the visualization of genetic inheritance in chromosomal context
No full textMotivation:
Data visualization is increasingly important in genomics, enabling researchers to uncover inheritance and recombination patterns across generations. While most existing tools focus on ancestry prediction, they lack functionality for analyzing known ancestries in controlled settings, such as determining parental contributions to offspring genomes. To address this gap, I developed pepa, a lightweight, deterministic, modular tool that visualizes and quantifies genomic inheritance, designed for beginner and advanced users.
Results:
pepa is a program for processing VCF files, assigning ancestries to homozygous SNPs, and clustering them into biologically meaningful regions. It generates human-readable comparison tables and visualizes inheritance patterns with chromosome paintings through R. Tested on fission yeast, pepa revealed non-uniform recombination patterns, with chromosomes largely inherited from one parent and seemingly random recombination. Quantitative analyses showed differences in parental contributions at the nucleotide and gene levels, with some offspring inheriting similar percentages from parents. However, the painted chromosomes revealed that even offspring with similar percentages from one parent rarely inherit the same genomic region, highlighting the importance of this tool in drawing biologically meaningful insights. pepa provides an accessible and powerful solution for analyzing genomic inheritance, bridging experimental and computational biology. Its modular design and minimal dependencies allow adaptation to diverse organisms, facilitating intuitive visualization and quantitative insights into recombination dynamics
Exploring water (in)securities in a water-abundant setting: hydrosocial dynamics and local strategies in Central-South Chile
No full textChile is experiencing complex hydrosocial crises, exacerbated by a prolonged period of drought. In the context of water scarcity and related resource conflicts, not only limited availability, but also questions of access to water play a crucial role. While most studies have focused on water insecurities in the semi-arid and arid regions of the country, less attention has been paid to southern Chile. However, the construction of hydropower plants in Indigenous territories has put a strain on relations between the state, the Mapuche populations and hydroelectric companies, and affected water availability in this part of the country.
Drawing on concepts of water security and environmental governance, we investigate water insecurities in seemingly water-abundant areas, using examples from the Los Rios region in Central-South Chile. Through qualitative social research methods including interviews and ethnographic observations conducted between 2019 and 2023, we found that problems of access to water surface within the green scenery affect population groups unequally. Based on the empirical case study, we argue that specific cultural, social and economic contexts influence decision-making processes regarding access to resources. Multiple factors limit or grant access to water, including financial issues, disputes within local communities and social networks, as well as the emergence of new economic activities, particularly tourism. In addition, a lack of coordination between governmental agencies at horizontal and vertical levels affects water governance. Therefore, our results are of socio-political relevance for possible reforms to water legislation and for the discourse on environmental justice and adaptive water governance
Volatile loss during heating of lunar mare simulants and related compositions
No full textDue to the scarcity of returned lunar regolith samples, simulants are currently widely used for testing and validation of technologies destined for resource extraction and manipulation on the Moon's surface. Deductions about thermal processing parameters (such as temperature ranges associated with sintering and melting) and material properties rely on a close fidelity of the terrestrially-sourced simulant materials. To evaluate the degassing behaviour of lunar regolith simulants during heating and thereby inform the validity of comparisons to the behaviour expected of actual lunar regolith, we compare profiles via simultaneous differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and evolved gas analysis (EGA) across a range of designated mare simulants, freshly recovered volcanic samples, and synthesised lunar-like glasses. Simulants generally exhibit higher mass loss (related to volatile release at sub-solidus temperatures) than fresh volcanic material, though overlap is observed with one simulant (JSC-1A). Of the fresh sources, Etna ash most closely limits the anticipated water loss difference to original lunar soils to within one order of magnitude. Results from complementary neutron powder diffraction (NPD) indicate that a lowering of the melting onset due to volatile fluxing persists ca. 200–300 °C beyond the major degassing range in samples of several grams. The possibility to reduce the simulant fidelity gap through critical source selection and their inherent limitations are discussed, and refined pre-treatment recommendations are made