gebhart/patrepeval huggingface dataset:
DIFFERENTIAL EXPRESSION OF SNORNAS IN CHONDROGENIC DIFFERENTIATION (2018)

Chondrogenic differentiation and cartilage homeostasis requires a high cellular translational capacity to meet the demands for cartilaginous extracellular matrix production. Box C/D and H/ACA snoRNAs guide post-transcriptional 2′-O ribose methylation and pseudouridylation of specific ribosomal RNA (rRNA) nucleotides, respectively. How specific rRNA modifications influence rRNA function is poorly documented, but modifications are thought to tune rRNA folding and interaction with ribosomal proteins, which is critical for ribosome function. We hypothesise that chondrocyte translational capacity is supported by snoRNA-mediated post-transcriptional fine-tuning of rRNAs. ATDC5 progenitor cells were differentiated into the chondrogenic lineage, resembling mature and mineralising chondrocytes after 7 or 14 days, respectively. UBF-1 (rRNA transcription factor), fibrillarin (box C/D methyltransferase) and dyskerin (box H/ACA pseudouridylase) expression displayed highest fold induction at day 5/6 in differentiation....
Mixed Initiative Interactive Edge Detection (2003)

We present an out-of-core mesh decimation algorithm that is able to handle input and output meshes of arbitrary size. The algorithm reads the input from a data stream in a single pass and writes the output to another stream while using only a fixed-sized in-core buffer. By applying randomized multiple choice optimization, we are able to use incremental mesh decimation based on edge collapses and the quadric error metric. The quality of our results is comparable to state-of-the-art high-quality mesh decimation schemes (which are slower than our algorithm) and the decimation performance matches the performance of the most efficient out-of-core techniques (which generate meshes of inferior quality).
Characterization of the Drosophila Sphingosine Kinases and Requirement for Sk2 in Normal Reproductive Function (2004)

Sphingosine kinase is a highly conserved enzyme that catalyzes the synthesis of sphingosine 1-phosphate and reduces cellular levels of sphingosine and ceramide. Although ceramide is pro-apoptotic and sphingosine is generally growth-inhibitory, sphingosine 1-phosphate signaling promotes cell proliferation, survival, and migration. Sphingosine kinase is thus in a strategic position to regulate important cell fate decisions which may contribute to normal animal development. To facilitate studies examining the potential role of sphingosine kinase and long chain base metabolism in Drosophila development, we characterized two putative Drosophila sphingosine kinase genes, Sk1 and Sk2. Both genes functionally and biochemically complement a yeast sphingosine kinase mutant, express predominantly cytosolic activities, and are capable of phosphorylating a range of endogenous and non-endogenous sphingoid base substrates. The two genes demonstrate overlapping but distinct temporal and spatial expression patterns in the Drosophila embryo, and timing of expression is consistent with observed changes in long chain base levels throughout development. A null Sk2 transposon insertion mutant demonstrated elevated long chain base levels, impaired flight performance, and diminished ovulation. This is the first reported mutation of a sphingosine kinase in an animal model; the associated phenotypes indicate that Sk1 and Sk2 are not redundant in biological function and that sphingosine kinase is essential for diverse physiological functions in this organism.
3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders (2017)

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.
Supplemental Figure 2. Kaplan Meier analysis of survival among MCPyV+ and MCPyV- patients according to the density, composition and distribution of the inflammatory infiltrate. from Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma (2023)

&lt;p&gt;Survival according to CD3 density/mm2 at the periphery (left), center (middle), and hotspot (right) in MCPyV+ MCCs (Top row) versus MCPyV- MCCs (Second row). Survival according to CD8 density/mm2 at the periphery (left), center (middle), and hotspot (right) in MCPyV+ MCCs. (Third Row) versus MCPyV- MCCs (Bottom row). Legend: Patients with cell densities above the median indicated with a dashed line and patients with cell density below the median indicated with a solid line.&lt;/p&gt;
Activation of adenosine receptor A2a by gut symbionts promotes immune tolerance (2021)

Abstract The gut microbiota is critical to immune homeostasis, but our understanding of the underlying molecular mechanisms is very limited. Here, we demonstrate a division of labor among members of the eight-membered “model microbiome” altered Schaedler flora in promoting distinct immunophenotypes. We report that Parabacteroides goldsteinii ASF519 induces immune tolerance by promoting interleukin (IL)-10 production in a variety of myeloid-derived immune cells. The IL-10 induction is dependent on the activation of adenosine receptor A2a by microbial enzymes of the methionine cycle. ASF519 colonization in mice increased the level of adenosine in ceca and induced IL-10 secreting dendritic cells in colonic lamina propria. These immunophenotypes were pharmacologically reversed by A2a blockage. In mouse models of human autoimmune diseases, ASF519 supplementation significantly ameliorated insulitis in type 1 diabetes and collagen-induced arthritis. This study unveils a novel paradigm of gut microbiota-adenosine receptor interactions in immune tolerance and potentially provides a new therapeutic strategy for immune disorders.
Deterministic Dicke-state preparation with continuous measurement and control (2004)

We characterize the long-time projective behavior of the stochastic master equation describing a continuous, collective spin measurement of an atomic ensemble both analytically and numerically. By adding state-based feedback, we show that it is possible to prepare highly entangled Dicke states deterministically.
Short and Scalable Synthesis of Plant‐Based Cholesterol in GMP Grade (2023)

Abstract A plant‐based straightforward and short four‐step synthesis of cholesterol starting from commercially available diosgenin is reported. This offers a large‐scale production of highly needed GMP‐grade cholesterol, which is part of the lipid cocktail for the assembly of effective mRNA‐based vaccines against the COVID‐19 pandemic. These lipids are formulated into the delivery system of the mRNA fragments by forming Lipid Nano Particles (LNP) that introduce the mRNA into the cells. Cholesterol plays a crucial role because it stabilizes LNP and facilitates endosome escape of the mRNA into the cytosol.
Probing the Influence of Single-Site Mutations in the Central Cross-β Region of Amyloid β (1–40) Peptides (2021)

Amyloid β (Aβ) is a peptide known to form amyloid fibrils in the brain of patients suffering from Alzheimer's disease. A complete mechanistic understanding how Aβ peptides form neurotoxic assemblies and how they kill neurons has not yet been achieved. Previous analysis of various Aβ<sub>40</sub> mutants could reveal the significant importance of the hydrophobic contact between the residues Phe<sub>19</sub> and Leu<sub>34</sub> for cell toxicity. For some mutations at Phe<sub>19</sub>, toxicity was completely abolished. In the current study, we assessed if perturbations introduced by mutations in the direct proximity of the Phe<sub>19</sub>/Leu<sub>34</sub> contact would have similar relevance for the fibrillation kinetics, structure, dynamics and toxicity of the Aβ assemblies. To this end, we rationally modified positions Phe<sub>20</sub> or Gly<sub>33</sub>. A small library of Aβ<sub>40</sub> peptides with Phe<sub>20</sub> mutated to Lys, Tyr or the non-proteinogenic cyclohexylalanine (Cha) or Gly<sub>33</sub> mutated to Ala was synthesized. We used electron microscopy, circular dichroism, X-ray diffraction, solid-state NMR spectroscopy, ThT fluorescence and MTT cell toxicity assays to comprehensively investigate the physicochemical properties of the Aβ fibrils formed by the modified peptides as well as toxicity to a neuronal cell line. Single mutations of either Phe<sub>20</sub> or Gly<sub>33</sub> led to relatively drastic alterations in the Aβ fibrillation kinetics but left the global, as well as the local structure, of the fibrils largely unchanged. Furthermore, the introduced perturbations caused a severe decrease or loss of cell toxicity compared to wildtype Aβ<sub>40</sub>. We suggest that perturbations at position Phe<sub>20</sub> and Gly<sub>33</sub> affect the fibrillation pathway of Aβ<sub>40</sub> and, thereby, influence the especially toxic oligomeric species manifesting so that the region around the Phe<sub>19</sub>/Leu<sub>34</sub> hydrophobic contact provides a promising site for the design of small molecules interfering with the Aβ fibrillation pathway.
Role of Na+ and Ca2+ Channels in the Preoptic LH Surge Generating Mechanism in Proestrous Rats (2003)

We studied whether Na+ and Ca2+ channels are involved in the neural mechanism responsible for the surge of gonadotropin-releasing hormone (GnRH) in proestrous rats. In experiment 1, female rats in proestrus were i.p. injected at 1345 h with pentobarbital sodium (35 mg/kg) to block spontaneous surge of LH and electrical stimulation was applied between 1400 and 1600 h to the preoptic area (POA) together with POA injection of 0.5 microl saline containing the Na+ channel blocker tetrodotoxin (TTX) at a concentration of 1 microM, 2 microM, or 5 microM. Since 5 microM TTX completely blocked the increase in serum LH concentrations evoked by the POA stimulation, we used this concentration in experiment 2 to observe the TTX effect on the spontaneous LH surge. In experiment 2, bilateral injections of 1.5 microl of 5 microM TTX at 1430 h in the POA in proestrous rats postponed the peak time and reduced the peak level of the LH surge. In experiment 3, bilateral injections of 1.5 microl of 5 microM L-type Ca2+ channel blocker nifedipine at 1430 h in the POA completely blocked the LH surge. Since the cell bodies of GnRH neurons are primarily concentrated in the POA in rats, these results suggest that both voltage-sensitive Na+ channels and Ca2+ channels contribute to the generation of action potentials at GnRH cell bodies for the surge release of GnRH.
Towards a Stronger Simulation Support for Engine Control Design: a Methodological Point of View (2007)

Thanks to a specific crank angle degree modelling approach and to an accurate simu-lator calibration, it is nowadays possible to build a complete simulator which allows the control engineer to access to numerous engine variables, especially non measurable values, and to perform tests over a wide range of operating conditions. Hosted in a dedicated platform, the engine simulator can support the control system design at each stage of the development cycle. Its use starts with the local dynamics understanding of the engine behaviour and ends with the real time control pre-calibration.
Reconnaissance de signaux sismiques d'avalanches par fusion de données estimées dans les domaines temps, temps-fréquence et polarisation (1996)

L'estimation de l'activite avalancheuse naturelle d'une portion de massif repose actuellement sur l'observation visuelle. Pour s'affranchir des contraintes de visibilite qui lui sont liees, une solution est de detecter les ondes sismiques produites par les avalanches au cours de leur chute. Cependant, 90 pour cent des signaux enregistres ne sont pas des avalanches et doivent etre elimines. Nous proposons une approche pluridisciplinaire de ce probleme de reconnaissance. Dans le domaine temps, le module du signal est utilise comme un premier critere de reconnaissance. Dans le domaine temps-frequence, la methode hybride arcap fournit une representation temps-frequence du signal avec une bonne reduction d'information. Dans le domaine de polarisation, nous proposons d'utiliser le filtre de capon pour ameliorer le rapport signal a bruit des signaux avant d'estimer un critere de linearite. Cela permet d'estimer la repartition dans le plan temps-frequence des mouvements lineaires contenus dans le signal. Le filtre de capon est etudie en detail et compare a un filtre de fourier. Les resultats de l'analyse sont reduits a environ 25 descripteurs qui, combines a l'aide d'une base de regles, permettent l'identification des signaux. Les regles sont inspirees principalement par des considerations sur les phenomenes physiques generateurs d'ondes sismiques et sur les lois de propagation. Un test sur un ensemble de signaux identifies permet d'evaluer le taux de reussite de notre systeme a environ 90 pour cent. Un prototype autonome est propose ; il sera installe sur site pour l'hiver 96/97. Une comparaison entre l'information fournie par notre systeme et d'autres donnees relatives a l'activite avalancheuse confirme l'interet de notre systeme pour des applications concretes
Spiking Deep Neural Networks: Engineered and Biological Approaches to Object Recognition (2018)

Modern machine learning models are beginning to rival human performance on some realistic object recognition tasks, but we still lack a full understanding of how the human brain solves this same problem. This thesis combines knowledge from machine learning and computational neuroscience to create models of human object recognition that are increasingly realistic both in their treatment of low-level neural mechanisms and in their reproduction of high-level human behaviour.&#13;\n&#13;\nFirst, I present extensions to the Neural Engineering Framework to make its preferred type of model---the “fixed-encoding” network---more accurate for object recognition tasks. These extensions include better distributions---such as Gabor filters---for the encoding weights, and better loss functions---namely weighted squared loss, softmax loss, and hinge loss---to solve for decoding weights.&#13;\n&#13;\nSecond, I introduce increased biological realism into deep convolutional neural networks trained with backpropagation, by training them to run using spiking leaky integrate-and-fire (LIF) neurons. These models have been successful in machine learning, and I am able to convert them to spiking networks while retaining similar levels of performance. I present a novel method to smooth the LIF rate response function in order to avoid the common problems associated with differentiating spiking neurons in general and LIF neurons in particular. I also derive a number of novel characterizations of spiking variability, and use these to train spiking networks to be more robust to this variability.&#13;\n&#13;\nFinally, to address the problems with implementing backpropagation in a biological system, I train spiking deep neural networks using the more biological Feedback Alignment algorithm. I examine this algorithm in depth, including many variations on the core algorithm, methods to train using non-differentiable spiking neurons, and some of the limitations of the algorithm. Using these findings, I construct a spiking model that learns online in a biologically realistic manner.&#13;\n&#13;\nThe models developed in this thesis help to explain both how spiking neurons in the brain work together to allow us to recognize complex objects, and how the brain may learn this behaviour. Their spiking nature allows them to be implemented on highly efficient neuromorphic hardware, opening the door to object recognition on energy-limited devices such as cell phones and mobile robots.
ComparativeN‐glycoproteomic analysis of Tibetan and lowland chicken fertilized eggs: Implications on proteins biofunction and species evolution (2021)

The characterization and functionality of protein glycosylation among different related species are of common interest. Herein, non-standard quantification and N-glycosylation enrichment technology combined with ultra-high liquid chromatography-tandem mass spectrometry were used to establish detailed N-glycoproteomics of fertilized eggs, and quantitatively compared between Tibetan and lowland chicken. A total of 396N-glycosites from 143 glycoproteins were found. Specifically, compared with lowland chicken egg white, 32N-glycosites of 22 glycoproteins were up-regulated and 57N-glycosites of 25 glycoproteins were down-regulated in Tibetan chicken egg white. Also, 137N-glycosites in 72 glycoproteins showed much higher-degree glycosylation and 36N-glycosites in 15 glycoproteins displayed lower-degree glycosylation in Tibetan chicken egg yolk than those in lowland chicken egg yolk. Through bioinformatic analysis, these varied glycoproteins were highly associated with antifreeze activity, hypoxia adaptation, coagulation cascade, and binding/immunity activities, which may be related to plateau hypoxia and cold stress. PRACTICAL APPLICATIONS: These findings provide a new insight on the role of biological egg N-glycoproteins related to environmental adaptation and evolution, which may be further applied in improving egg processing and human health, by developing biomolecules for food and medical industry.
Virtual Quantification of Metabolites by Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry: Predicting Ionization Efficiency Without Chemical Standards (2009)

A major obstacle in metabolomics remains the identification and quantification of a large fraction of unknown metabolites in complex biological samples when purified standards are unavailable. Herein we introduce a multivariate strategy for de novo quantification of cationic/zwitterionic metabolites using capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) based on fundamental molecular, thermodynamic, and electrokinetic properties of an ion. Multivariate calibration was used to derive a quantitative relationship between the measured relative response factor (RRF) of polar metabolites with respect to four physicochemical properties associated with ion evaporation in ESI-MS, namely, molecular volume (MV), octanol-water distribution coefficient (log D), absolute mobility (mu(o)), and effective charge (z(eff)). Our studies revealed that a limited set of intrinsic solute properties can be used to predict the RRF of various classes of metabolites (e.g., amino acids, amines, peptides, acylcarnitines, nucleosides, etc.) with reasonable accuracy and robustness provided that an appropriate training set is validated and ion responses are normalized to an internal standard(s). The applicability of the multivariate model to quantify micromolar levels of metabolites spiked in red blood cell (RBC) lysates was also examined by CE-ESI-MS without significant matrix effects caused by involatile salts and/or major co-ion interferences. This work demonstrates the feasibility for virtual quantification of low-abundance metabolites and their isomers in real-world samples using physicochemical properties estimated by computer modeling, while providing deeper insight into the wide disparity of solute responses in ESI-MS. New strategies for predicting ionization efficiency in silico allow for rapid and semiquantitative analysis of newly discovered biomarkers and/or drug metabolites in metabolomics research when chemical standards do not exist.
Misconceptions of Mexican Teachers in The Solution of Simple Pendulum (2013)

Solving the position of a simple pendulum at any time is apparently one of the most simple and basic problems to solve -in high school and college physics courses. However, because of this apparent simplicity, teachers and physics texts often assume that the solution is immediate -without pausing to reflect on the problem formulation or verifying that the solution obtained is indeed correct. This process causes conceptual errors to be carried out with them -students and even worse teachers. This paper presents some of the misconceptions found in teachers solving simple pendulum problems, moreover it presents proposals made in the texts, which generate the creation of such misconceptions in both teachers and students, and finally, it presents the proposal of a solution to correct this problem.
New properties of the Radon transform of the cross Wigner/ambiguity distribution function (1999)

In this correspondence, we prove that the Radon transform of the cross Wigner distribution function is a separable multiplication of fractional Fourier transforms of these functions. Thus, the 2-D cross ambiguity function is a surface of fractional correlation for 1-D signals, each associated with the angle of observation over the surface.
An azido-bridged [FeII4] grid-like molecule showing spin crossover behaviour (2021)

The supramolecular self-assembly synthetic strategy provides a valid tool to obtain polynuclear Fe(II) complexes having effective communication between the metal centres and distinct spin crossover behaviour. Despite the great success in constructing various magnetic molecules, progress has not been made in SCO complexes based on azido bridges. In this article, the coordination-driven supramolecular assembly based on 3,6-substituted pyridazine and azide is presented to afford two Fe(II) grid-like complexes: [(L)<sub>4</sub>FeII4(N<sub>3</sub>)<sub>4</sub>][BPh<sub>4</sub>]<sub>4</sub>·sol (1, L = 3,6-bis(3,5-dimethyl-1<i>H</i>-pyrazol-1-yl)pyridazine and 2, L = 3,6-di(pyridin-2-yl)pyridazine). The substitution of pyridinyl groups in 2 instead of pyrazolyl ones in 1 led to the only example exhibiting spin-crossover behaviour (<i>T</i><sub>1/2</sub> = 230 K) among the azido-bridged complexes. In addition, a temperature-dependent photoluminescence study of 2 demonstrates a visible synergetic effect between the SCO event and the luminescence.
Controlled Release Technology Suppresses the Progression of Disseminated Pancreatic Cancer Cells (2005)

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