In this study we compare and evaluate different unsupervised clustering algorithms for organofacies discrimination in low maturity dispersed organic matter based on Raman spectroscopic analyses. A ...total of 1363 Raman spectra were collected from a set of 27 organic-rich samples from the Lower Toarcian shale interval of the Paris Basin sub-surface. Rock-Eval pyrolysis data indicate a type II to type III kerogen with a vitrinite reflectance (Ro%) between 0.45% and 0.65%, and Tmax between 415 °C and 438 °C. Organic petrographic observations under transmitted light reveal the presence of organofacies composed by amorphous organic matter, opaque, and translucent phytoclasts. An optical classification of organic particles was performed on about 40–60 fragments per sample and used as the ground truth. Raman spectra were obtained for all the classified fragments and principal component analysis was performed to underline the variability among spectra. Unsupervised clustering was then applied on Raman spectra principal components. Three clustering methods were applied to evaluate their effectiveness in predicting number, shape and density of clusters and a contingency matrix was used to quantify their ability to predict different organofacies. Gaussian Mixture Model (GMM) was found to be the best algorithm for organofacies identification showing an accuracy mostly between 80% and 90%. This work outlines how unsupervised clustering of Raman spectra of dispersed organic matter can reduce the uncertainty in thermal maturity assessment and help the classification of highly heterogeneous organofacies when using large datasets for Earth and planetary sciences studies.
•Raman spectroscopy may characterize dispersed organic matter.•Raman spectra variability in a sample can be studied by principal component analysis.•Unsupervised clustering can be performed on Raman spectra principal components.•Gaussian Mixture Model algorithm allows best organofacies discrimination.
The advent of stem cell-derived retinal organoids has brought forth unprecedented opportunities for developmental and physiological studies, while presenting new therapeutic promise for retinal ...degenerative diseases. From a translational perspective, organoid systems provide exciting new prospects for drug discovery, offering the possibility to perform compound screening in a three-dimensional (3D) human tissue context that resembles the native histoarchitecture and to some extent recapitulates cellular interactions. However, inherent variability issues and a general lack of robust quantitative technologies for analyzing organoids on a large scale pose severe limitations for their use in translational applications. To address this need, we have developed a screening platform that enables accurate quantification of fluorescent reporters in complex human iPSC-derived retinal organoids. This platform incorporates a fluorescence microplate reader that allows
-dimensional detection and fine-tuned wavelength selection. We have established optimal parameters for fluorescent reporter signal detection, devised methods to compensate for organoid size variability, evaluated performance and sensitivity parameters, and validated this technology for functional applications.
We investigated calcites and dolomites precipitated during burial diagenesis of the Upper Triassic (Norian) continental siliciclastics from sub‐surface reservoirs of the northern Paris Basin (Chaunoy ...Formation) that experienced a thermal maximum >100°C during Late Cretaceous times. Relative carbonate precipitation timing was established via petrographic analyses. The diagenetic carbonates were further investigated by fluid inclusion and clumped isotope (Δ47) thermometry. The two thermometric datasets were interpreted by evaluating the possible occurrence of inclusion thermal reequilibration and Δ47 solid‐state reordering, based on the known basin thermal history and the three existing Δ47 reordering models. By considering the fluid inclusion and Δ47 datasets obtained and the various Δ47 reordering models, different carbonate precipitation scenarios, in terms of timing and parent fluid composition (δ18Ofluid), were inferred. These results underline that in samples having experienced thermal maximum >100°C, accuracy and interpretation of fluid inclusion and Δ47 thermometry data (especially on calcite) may be biased by thermal reequilibration and solid‐state reordering. The results converge towards the need of jointly applying fluid inclusion and Δ47 thermometry on the same carbonate phases to evaluate all the possible precipitation scenarios. The most likely carbonate precipitation scenarios, based on Δ47 thermometry data, point at the precipitation of two calcite phases during Early to Late Jurassic times and of one dolomite phase during the Late Cretaceous. The parent fluids possibly were original formation waters of the Chaunoy Fm. that mixed with brines migrating from the East, where time equivalent evaporitic deposits occur. The proposed precipitation model for calcites and dolomites, involving different pulses of brine migration, and the dominance of calcite phases were not recorded by previous studies on the Upper Triassic units. These latter results may be of interest to evaluate the reservoir potential of the Chaunoy Fm. in this underexplored portion of the Paris Basin.
Precipitation timing and δ18Ofluid for the studied diagenetic carbonates obtained from different temperature datasets (fluid inclusions, ∆47).
Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the effectiveness of SARI sentinel ...surveillance for total and severe cases incidence estimation. Leveraging data from the COVID-19 pandemic in Chile, we examined 2020-2023 data (a 159-week period) comparing census surveillance results of confirmed cases and hospitalizations, with sentinel surveillance. Our analyses revealed a consistent underestimation of total cases and an overestimation of severe cases of sentinel surveillance. To address these limitations, we introduce a nowcasting model, improving the precision and accuracy of incidence estimates. Furthermore, the integration of genomic surveillance data significantly enhances model predictions. While our findings are primarily focused on COVID-19, they have implications for respiratory virus surveillance and early detection of respiratory epidemics. The nowcasting model offers real-time insights into an outbreak for public health decision-making, using the same surveillance data that is routinely collected. This approach enhances preparedness for emerging respiratory diseases by the development of practical solutions with applications in public health.
The cumulative knowledge of retina development has been instrumental in the generation of retinal organoid systems from pluripotent stem cells; and these three-dimensional organoid models, in turn, ...have provided unprecedented opportunities for retinal research and translational applications, including the ability to model disease in a human setting and to apply these models to the development and validation of therapeutic drugs. In this review article, we examine how retinal organoids can also contribute to our understanding of retinal developmental mechanisms, how this knowledge can be applied to modeling developmental abnormalities, and highlight some of the avenues that remain to be explored.
Abstract
The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the ...daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction. Yet, despite this high prevalence, long-term, effective treatments for these disorders have been largely elusive. Clinical successes in other sensory systems, including hearing and vision, have led to new hope for developments in the treatment of chemosensory disorders. To accelerate cures, we convened the “Identifying Treatments for Taste and Smell Disorders” conference, bringing together basic and translational sensory scientists, health care professionals, and patients to identify gaps in our current understanding of chemosensory dysfunction and next steps in a broad-based research strategy. Their suggestions for high-yield next steps were focused in 3 areas: increasing awareness and research capacity (e.g., patient advocacy), developing and enhancing clinical measures of taste and smell, and supporting new avenues of research into cellular and therapeutic approaches (e.g., developing human chemosensory cell lines, stem cells, and gene therapy approaches). These long-term strategies led to specific suggestions for immediate research priorities that focus on expanding our understanding of specific responses of chemosensory cells and developing valuable assays to identify and document cell development, regeneration, and function. Addressing these high-priority areas should accelerate the development of novel and effective treatments for taste and smell disorders.
Alzheimer's disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of ...phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aβ and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This
model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies.
The embryonic chick occupies a privileged place among animal models used in developmental studies. Its rapid development and accessibility for visualization and experimental manipulation are just ...some of the characteristics that have made it a vertebrate model of choice for more than two millennia. Until a few years ago, the inability to perform genetic manipulations constituted a major drawback of this system. However, the completion of the chicken genome project and the development of techniques to manipulate gene expression have allowed this classic animal model to enter the molecular age. Such techniques, combined with the embryological manipulations that this system is well known for, provide a unique toolkit to study the genetic basis of neural development. A major advantage of these approaches is that they permit targeted gene misexpression with extremely high spatiotemporal resolution and over a large range of developmental stages, allowing functional analysis at a level, speed and ease that is difficult to achieve in other systems. This article provides a general overview of the chick as a developmental model focusing more specifically on its application to the study of eye development. Special emphasis is given to the state of the art of the techniques that have made gene gain- and loss-of-function studies in this model a reality. In addition, we discuss some methodological considerations derived from our own experience that we believe will be beneficial to researchers working with this system.
PDF
