julilili42/papers huggingface dataset:
HIT-IgGs induce a heparin-dependent pro-thrombotic phenotype in a novel endothelialized microfluidic disease model
2024-02-01

Introduction Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin. Heparin/PF4/IgG complexes have been reported to activate platelets, neutrophils, and possibly endothelial cells, resulting in thrombocytopenia, hypercoagulability and thromboembolic complications. While the impact of anti-PF4/heparin antibodies on blood cell activation has been extensively studied, the role of endothelial cells in HIT-associated thrombosis remains underexplored. In particular, the interactions between HIT-induced procoagulancy and endothelial cells under flow conditions is not completely elucidated. In this report, we investigated how HIT antibodies induce thrombosis in an endothelialized microfluidic system.
Decoding Blood Platelet Production: The Intricate Role of Lipids
2024-02-01

Introduction During megakaryopoiesis and consecutive platelet production, megakaryocytes undergo cellular morphological changes which are associated with the reprogramming of signaling pathways. Moreover, membrane composition and lipid signaling are expected to be strongly modified. However, the knowledge of how lipids are modulated and which pathways are involved is still lacking.
A POWHEG generator for deep inelastic scattering
2024-02-02

A bstract We present a new event generator for the simulation of both neutral- and charged-current deep inelastic scattering (DIS) at next-to-leading order in QCD matched to parton showers using the POWHEG method. Our implementation builds on the existing POWHEG BOX framework originally designed for hadron-hadron collisions, supplemented by considerable extensions to account for the genuinely different kinematics inherent to lepton-hadron collisions. In particular, we present new momentum mappings that conserve the special kinematics found in DIS, which we use to modify the POWHEG BOX implementation of the Frixione-Kunszt-Signer subtraction mechanism. We compare our predictions to fixed-order and resummed predictions, as well as to data from the HERA ep collider. Finally we study a few representative distributions for the upcoming Electron Ion Collider.
Pizza Oven Processing of Organohalide Perovskites (POPOP): A Simple, Versatile and Efficient Vapor Deposition Method
2024-02-02

Abstract Hybrid vapor deposition is one of the most appealing processes for perovskite photovoltaics fabrication, thanks to its versatile nature. By using sequentially different vapor deposition processes tailored to the inorganic and organic perovskite precursors' peculiarities, this type of process gives access to the full potential of vapor deposition. While vapor deposition of metal halides is well understood and mastered, vapor deposition of organohalide species is much more delicate (degradation of vapors, high vapor pressure, setup‐specific constraints). Here, a novel close space sublimation system is reported and in‐depth insights on the conversion into perovskite of a metal halide template are provided. In this evolution of the process, the substrate coated with metal halide template and the organohalide source are loaded together in a dedicated holder, then transferred into a vacuum chamber on a heating element already at temperature setpoint. The system enables a simple, fast, low‐cost, and easy‐to‐reproduce organohalide vapor deposition process. The formation of the perovskite in situ and identification different conversion regimes are studied. Furthermore, the influence of the chemical environment and chamber design on the process are discussed. Compositional tuning and additive engineering in the process are processed and fabricate proof of concept photovoltaic devices reaching high fill factors of 80% and 17% power conversion efficiency for a bandgap of 1.63 eV.
Constructing tests for skill assessment with competence‐based test development
2024-02-02

Abstract Competence‐based test development is a recent and innovative method for the construction of tests that are as informative as possible about the competence state (the set of skills an individual has available) underlying the observed item responses. It finds application in different contexts, including the development of tests from scratch, and the improvement or shortening of existing tests. Given a fixed collection of competence states existing in a population of individuals and a fixed collection of competencies (each of which being the subset of skills that allow for solving an item), the competency deletion procedure results in tests that differ from each other in the competencies but are all equally informative about individuals' competence states. This work introduces a streamlined version of the competency deletion procedure that considers information necessary for test construction only, illustrates a straightforward way to incorporate test developer preferences about competencies into the test construction process, and evaluates the performance of the resulting tests in uncovering the competence states from the observed item responses.
The subtilisin-like protease furin regulates hemin-induced CD63 surface expression on platelets
2024-02-02

Accumulation of free heme B in the plasma can be the result of severe hemolytic events, when the scavenger system for free hemoglobin and heme B is overwhelmed. Free heme B can be oxidized into toxic hemin, which has been proven to activate platelet degranulation and aggregation and promote thrombosis. In the present study we analyzed the effect of hemin on the activation-mediated lysosomal degranulation and CD63 surface expression on platelets using classic flow cytometry and fluorescence microscopy techniques. Classical platelet activators were used as control to distinguish the novel effects of hemin from known activation pathways. CD63 is a tetraspanin protein, also known as lysosomal-associated membrane protein 3 or LAMP-3. In resting platelets CD63 is located within the membrane of delta granules and lysosomes of platelet, from where it is integrated into the platelet outer membrane upon stimulation. We were able to show that hemin like the endogenous platelet activators ADP, collagen or thrombin does provoke CD63 re-localization. Interestingly, only hemin-induced CD63 externalization is dependent on the subtilisin-like pro-protein convertase furin as shown by inhibitor experiments. Furthermore, we were able to demonstrate that hemin induces lysosome secretion, a source of the hemin-mediated CD63 presentation. Again, only the hemin-induced lysosome degranulation is furin dependent. In summary we have shown that the pro-protein convertase furin plays an important role in hemin-mediated lysosomal degranulation and CD63 externalization.
Photoluminescence emission and Raman enhancement in TERS: an experimental and analytic revisiting
2024-02-02

Abstract An analytic model is used to calculate the Raman and fluorescence enhancement of a molecule in between two closely spaced gold nanospheres. Instead of using the conventional approach that only the dipolar plasmonic mode is considered, we calculate the electric field enhancement in the nanometre sized gap, by taking account of the higher order modes in one gold sphere, which couples to the dipolar mode of the other sphere. The experimental confirmation is performed by gap-dependent tip-enhanced Raman spectroscopy (TERS) measurements. The photoluminescence and Raman enhancement are both observed with different growing trends as the gap width decreases. Red-shift of the background spectra is observed and implies the increasing coupling between the nanospheres. This analytic model is shown to be able to interpret the enhancement mechanisms underlying gap-dependent TERS experimental results.
Assessing the Role of Facial Symmetry and Asymmetry between Partners in Predicting Relationship Duration: A Pilot Deep Learning Analysis of Celebrity Couples
2024-02-02

Prevailing studies on romantic relationships often emphasize facial symmetry as a factor in partner selection and marital satisfaction. This study aims to explore the inverse of this hypothesis—the relationship between facial dissimilarity and partnership duration among celebrity couples. Utilizing the CELEB-A dataset, which includes 202,599 images of 10,177 celebrities, we conducted an in-depth analysis using advanced artificial intelligence-based techniques. Deep learning and machine learning methods were employed to process and evaluate facial images, focusing on dissimilarity across various facial regions. Our sample comprised 1822 celebrity couples. The predictive analysis, incorporating models like Linear Regression, Ridge Regression, Random Forest, Support Vector Machine, and a Neural Network, revealed varying degrees of effectiveness in estimating partnership duration based on facial features and partnership status. However, the most notable performance was observed in Ridge Regression (Mean R2 = 0.0623 for whole face), indicating a moderate predictive capability. The study found no significant correlation between facial dissimilarity and partnership duration. These findings emphasize the complexity of predicting relationship outcomes based solely on facial attributes and suggest that other nuanced factors might play a more critical role in determining relationship dynamics. This study contributes to the understanding of the intricate nature of partnership dynamics and the limitations of facial attributes as predictors.
Excited States Dynamics at Pentacene/Perfluoropentacene Interfaces: A Femtosecond Time‐Resolved Second Harmonic Generation Study
2024-02-02

Abstract Understanding the dynamics of excited states after optical excitation at donor‐acceptor (D/A) interfaces is of paramount importance for improving the efficiency and performance of optoelectronic devices. Here, we studied the ultrafast excited state dynamics after optical excitation at interfaces between the electron donor (D) pentacene (PEN) and the electron acceptor (A) perfuoropentacene (PFP) as well as within the single compounds (PEN and PFP) using femtosecond (fs) time‐resolved second harmonic generation (SHG). In the single compounds singlet fission is observed on a time scale of around 200 fs. In the bilayer systems a huge SHG intensity rise is observed due to the creation of charge transfer states at the interface and accordingly to formation of a local electric field within tens of picoseconds. The local electric field and therefore the SHG signal intensity from the interface of PEN/PFP bilayer is much more intense compared to the PFP/PEN system because the PFP and PEN intermixing at the PEN/PFP interface is higher. Accordingly a population of defect states on a time scale of 55±12 ps has been proposed for PEN/PFP. Our study provides important insights into D/A charge transfer properties, which is needed for the understanding of the interfacial photophysics of pentacene‐based organic compounds.
Early Holocene human occupations in the western Tian Shan (Central Asia): Insights from the Alpysbaev Cave
2024-02-02

The Early Holocene archaeology of Central Asia (particularly the Pamir-Alay and Western Tian Shan ranges) has recently revealed valuable insights regarding the patterns of human occupation and adaptations strategies in diverse landscapes. Until recently, the Kazakh portion of the western Tian Shan remained devoid of Neolithic sites, hindering the interpretation of human occupations in the region during the Early Holocene. In this paper, we present the initial results of the newly excavated site of Alpysbaev Cave located in Turkestan Province, southern Kazakhstan. Test excavations yielded several pits intersecting one another and containing disturbed human remains (three male adults and a neonate) as well as ceramic sherds, lithics, and a combustion feature. The lowermost lithostratigraphic unit contained human cranial fragments and faunal remains. Radiocarbon dating and the preliminary analysis of the finds suggest at least three occupation phases spanning from the early medieval to the Late Iron Age burials and the oldest layers dating to the Early Neolithic periods.
[18F]pFBC, a Covalent CLIP-Tag Radiotracer for Detection of Viral Reporter Gene Transfer in the Murine Brain
2024-02-03

Preclinical models of neurological diseases and gene therapy are essential for neurobiological research. However, the evaluation of such models lacks reliable reporter systems for use with noninvasive imaging methods. Here, we report the development of a reporter system based on the CLIP-tag enzyme and [<sup>18</sup>F]<i>p</i>FBC, an <sup>18</sup>F-labeled covalent CLIP-tag-ligand synthesized via a DoE-optimized and fully automated process. We demonstrated its specificity using a subcutaneous xenograft model and a model of viral vector-mediated brain gene transfer by engineering HEK293 cells and striatal neurons to express membrane-tethered CLIP-tag protein. After <i>in vitro</i> characterization of the reporter, mice carrying either CLIP-tag expressing or control subcutaneous xenografts underwent dynamic [<sup>18</sup>F]<i>p</i>FBC PET imaging. The CLIP-tag expressing xenografts showed a significantly higher uptake than control xenografts (tumor-to-muscle ratio 5.0 vs 1.7, p = 0.0379). <i>In vivo</i>, metabolite analysis by radio-HPLC from plasma and brain homogenates showed only one radio-metabolite in plasma and none in the brain. In addition, [<sup>18</sup>F]<i>p</i>FBC showed fast uptake and rapid clearance from the brain in animals injected with adeno-associated virus (AAV)-CLIP in the right striatum but no right-to-left (R-L) uptake difference in the striata in the acquired PET data. In contrast, autoradiography showed a clear accumulation of radioactivity in the AAV-CLIP-injected right striatum compared to the sham-injected left striatum control. CLIP-tag expression and brain integrity were verified by immunofluorescence and light sheet microscopy. In conclusion, we established a novel reporter gene system for PET imaging of gene expression in the brain and periphery and demonstrated its potential for a wide range of applications, particularly for neurobiological research and gene therapy with viral vectors.
Distribution of Acetogenic Naphthoquinones in Droseraceae and Their Chemotaxonomic Utility
2024-02-03

Chemotaxonomy is the link between the state of the art in analytical chemistry and the systematic classification and phylogenetic analysis of biota. Although the characteristic secondary metabolites from diverse biotic sources have been used in pharmacology and biological systematics since the dawn of mankind, only comparatively recently established reproducible methods have allowed the precise identification and distinction of structurally similar compounds. Reliable, rapid screening methods like TLC (Thin Layer Chromatography) can be used to investigate sufficiently large numbers of samples for chemotaxonomic purposes. Using distribution patterns of mutually exclusive naphthoquinones, it is demonstrated in this review how a simple set of chemical data from a representative sample of closely related species in the sundew family (Droseraceae, Nepenthales) provides taxonomically and phylogenetically informative signal within the investigated group and beyond.
Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients
2024-02-04

We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally enabled the characterization and quantification of the most abundant serum metabolites, showing the potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine- and uracil-based) analogue structures, eight of which were previously unknown in humans <i>allowing us to propose a new extended viperin pathway for the innate production of antiviral compounds</i>. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ, and IL-10, suggest an association with the viperin enzyme contributing to an ancient endogenous innate immune defense mechanism against viral infection.
Optical Emission Spectroscopy for the Real-Time Identification of Malignant Breast Tissue
2024-02-04

Breast conserving resection with free margins is the gold standard treatment for early breast cancer recommended by guidelines worldwide. Therefore, reliable discrimination between normal and malignant tissue at the resection margins is essential. In this study, normal and abnormal tissue samples from breast cancer patients were characterized ex vivo by optical emission spectroscopy (OES) based on ionized atoms and molecules generated during electrosurgical treatment. The aim of the study was to determine spectroscopic features which are typical for healthy and neoplastic breast tissue allowing for future real-time tissue differentiation and margin assessment during breast cancer surgery. A total of 972 spectra generated by electrosurgical sparking on normal and abnormal tissue were used for support vector classifier (SVC) training. Specific spectroscopic features were selected for the classification of tissues in the included breast cancer patients. The average classification accuracy for all patients was 96.9%. Normal and abnormal breast tissue could be differentiated with a mean sensitivity of 94.8%, a specificity of 99.0%, a positive predictive value (PPV) of 99.1% and a negative predictive value (NPV) of 96.1%. For 66.6% patients all classifications reached 100%. Based on this convincing data, a future clinical application of OES-based tissue differentiation in breast cancer surgery seems to be feasible.
First results from the LAPPDs in ANNIE
2024-02-04

The Accelerator Neutrino Neutron Interaction Experiment (ANNIE) is a 26-ton gadolinium-dopedwater Cherenkov detector with a submerged water-based liquid scintillator filled vessel. It is on-axis of the Booster Neutrino Beam (BNB) at Fermilab, and its main physics goal is to measurethe neutrino cross-section which will improve the systematic uncertainties of next-generationlong-baseline neutrino experiments. The first such measurement will be the final state neutronmultiplicity of neutrino-nucleus interactions in water. ANNIE is also the first large-scale highenergy physics experiment to deploy multiple Large Area Picosecond Photodetectors (LAPPD), anovel photon detector technology with a timing resolution of &lt;100 ps and a sub-centimeter spatialresolution which will help to improve the vertex reconstruction. This work will give an updateon the status of the LAPPD deployment as well as first results from neutrino beam induced eventsrecorded by the LAPPDs.
Jag1 represses Notch activation in lateral supporting cells and inhibits an outer hair cell fate in the medial compartment of the developing cochlea
2024-02-04

Abstract Notch signaling regulates both inner and middle ear morphogenesis and establishes a strict pattern of sensory cells in the organ of Corti in the mammalian cochlea. Patients with Alagille syndrome have impaired Notch signaling (∼94% with JAG1 mutations) resulting in sensorineural and conductive hearing loss. Here, we investigate the function of Jag1-mediated Notch activation in cochlear patterning and signaling using the Jag1 “Nodder” ( Jag1 Ndr/Ndr ) mouse model of Alagille syndrome. Jag1 Ndr/Ndr mice exhibited severe vestibular and auditory deficits and a dose-dependent increase in ectopic inner hair cells and a reduction in outer hair cells. Single cell RNA sequencing of the organ of Corti demonstrated a global dysregulation of genes associated with inner ear development and deafness. Analysis of individual cell types indicated a novel role for Jag1 in repressing Notch activation in lateral supporting cells and revealed a function for Jag1 in gene regulation and development of outer hair cells. Additionally, “outer hair cell-like” SLC26A5 (Prestin) positive cells were present in the medial compartment and pillar cell region of Jag1 Ndr/Ndr mice and exhibited location-dependent expression of the inner hair cell fate-regulator Tbx2 , revisiting the potency of Tbx2 in driving inner hair cell commitment in “outer hair cell-like” cells in the Jag1-mutant IHC compartment. Our data reveals a novel role for Jag1 in repressing Notch activation in lateral supporting cells and highlights involvement for Notch signaling in inner versus outer hair cell specification and positioning.
Failing Forward in European Economic Governance: The Cyclicality of European Integration and Institutional Competition in the COVID‐19 Crisis
2024-02-04

Abstract The European Union's (EU's) response to the pandemic has been accompanied by reconfigurations in its institutional hierarchy, affecting the sites where institutional reforms are prepared and implemented. Whereas the Eurogroup drove reform during the euro crisis, the Commission had a more pronounced role in the development and implementation of pandemic instruments. This article ties in with failing‐forward arguments that view European integration as cyclical, arguing that this cyclicality also concerns the institutional dynamics in European economic governance. Based on expert interviews, official documents and reports, the analysis reconstructs and compares the institutional configurations during the euro crisis and the pandemic. Its findings suggest three modifications to ‘failing forward’: first, incomplete intergovernmental decisions are often the result of dominant particular interests rather than ‘lowest common denominator’ solutions; second, supranational bodies can exploit the delegitimization of intergovernmental solutions; and third, ad hoc measures can prolong the failing‐forward cycle and displace lasting integration steps.
Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper
2024-02-05

Background With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. Methods and Results The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. Conclusion Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.