julilili42/papers huggingface dataset:
(130) Elektra Delta – on the stability of the new third moonlet
2023-05-03

ABSTRACT The aim of this work is to verify the stability of the proposed orbital solutions for the third moonlet (Delta) taking into account a realistic gravitational potential for the central body of the quadruple system (Alpha). We also aim to estimate the location and size of a stability region inside the orbit of Gamma. First, we created a set of test particles with intervals of semimajor axis, eccentricities, and inclinations that covers the region interior to the orbit of Gamma, including the proposed orbit of Delta and a wide region around it. We considered three different models for the gravitational potential of Alpha: irregular polyhedron, ellipsoidal body, and oblate body. For a second scenario, Delta was considered a massive spherical body and Alpha an irregular polyhedron. Beta and Gamma were assumed as spherical massive bodies in both scenarios. The simulations showed that a large region of space is almost fully stable only when Alpha was modelled simply as an oblate body. For the scenario with Delta as a massive body, the results did not change from those as mass-less particles. Beta and Gamma do not play any relevant role in the dynamics of particles interior to the orbit of Gamma. Delta’s predicted orbital elements are fully unstable and far from the nearest stable region. The primary instability source is Alpha’s elongated shape. Therefore, in the determination of the orbital elements of Delta, it must be taken into account the gravitational potential of Alpha assuming, at least, an ellipsoidal shape.
The Influence of the Side Chain Structure on the Photostability of Low Band Gap Polymers
2023-05-03

Side chains play an important role in the photo-oxidation process of low band gap (LBG) polymers. For example, it has been shown that their photostability can be increased by the introduction of aromatic-oxy-alkyl links. We studied the photostability of prototypical LBG polymers with alkyl and oxyalkyl side chains during irradiation with white light (AM 1.5 conditions) in dry air using UV/vis and IR spectroscopy. Though its degradation kinetics were distinctly affected by the presence or absence of oxygen in the structure of the side chains, in particular cases, the stability was more affected by the presence of linear or branched side chains. Moreover, we showed that the exact position of the alkyl/oxyalkyl side chain at the polymer backbone could be crucial. Although minor effects of chemical modifications on the electronic parameters (ionization potential and gap) were observed, the molecular orientation, determined by polarization modulation-infrared reflection-absorption spectroscopy (PMIRRAS), could be affected. The aggregation and crystallinity of these polymers may distinctly affect their stability.
A unified framework towards diagnostic test development and evaluation during outbreaks of emerging infections
2023-05-03

<title>Abstract</title> <bold>Background</bold> Diagnostic tests play a crucial role during an epidemic or a pandemic, both for individual patient care, and as a tool in population-level non-pharmaceutical interventions. The development and evaluation of such tests during epidemics faces numerous challenges, including short timeframes, and changing disease prevalence, pathogen characteristics, and testing applications. In this position paper, we describe these challenges through an interdisciplinary lens and present potential solutions, based on experiences during the SARS-CoV-2 pandemic. <bold>Methods </bold>We conducted a workshop that brought together experts from various disciplines involved in diagnostic test development and evaluation, from molecular test development to public health decision-making. The challenges and potential solutions we discuss are derived from discussions had and conclusions drawn in the workshop. <bold> Results </bold>We identified a feedback loop between evaluation of test accuracy, integration of test accuracy estimates in modelling studies for public health decision-making, and population-level interventions that determine testing strategies, and can define how diagnostic tests might need re-evaluation. Incorporating this feedback loop into test evaluation can help diagnostic test development be optimised for both individual patient care and population level measures. Furthermore, adaptive and seamless designs for diagnostic studies provide a promising methodological solution to narrow timeframes and the need for continuous re-evaluation of diagnostic tests during epidemic or pandemic situations.<bold> Conclusions </bold>We present a framework for diagnostic test development and evaluation that acknowledges the feedback loop between diagnostic test studies and infectious disease modelling studies, and provides solutions to challenges faced in test development and evaluation during outbreaks of emerging infectious agents.
Studying Between-Subject Differences in Trends and Dynamics: Introducing the Random Coefficients Continuous-Time Latent Curve Model with Structured Residuals
2023-05-03

The recently proposed <i>continuous-time latent curve model with structured residuals</i> (CT-LCM-SR) addresses several challenges associated with longitudinal data analysis in the behavioral sciences. First, it provides information about process trends and dynamics. Second, using the continuous-time framework, the CT-LCM-SR can handle unequally spaced measurement occasions and describes processes independently of the length of the time intervals used in a given study. Third, it is a hierarchical model. Thus, multiple subjects can be analyzed simultaneously. However, subjects might also differ in dynamics and trends. Therefore, in the present paper, we extend the CT-LCM-SR to capture these differences as well. This newly proposed <i>random coefficients continuous-time latent curve model with structured residuals</i> (RC-CT-LCM-SR) is introduced theoretically and technically. Additionally, we provide an illustrative example with data from the Health and Retirement Study (HRS), and we show how the RC-CT-LCM-SR can be used to study multiple sources of between-subject differences over time.
Development of an Anticipatory Triage-Ranking Algorithm Using Dynamic Simulation of the Expected Time Course of Patients With Trauma: Modeling and Simulation Study
2023-05-04

Background In cases of terrorism, disasters, or mass casualty incidents, far-reaching life-and-death decisions about prioritizing patients are currently made using triage algorithms that focus solely on the patient’s current health status rather than their prognosis, thus leaving a fatal gap of patients who are under- or overtriaged. Objective The aim of this proof-of-concept study is to demonstrate a novel approach for triage that no longer classifies patients into triage categories but ranks their urgency according to the anticipated survival time without intervention. Using this approach, we aim to improve the prioritization of casualties by respecting individual injury patterns and vital signs, survival likelihoods, and the availability of rescue resources. Methods We designed a mathematical model that allows dynamic simulation of the time course of a patient’s vital parameters, depending on individual baseline vital signs and injury severity. The 2 variables were integrated using the well-established Revised Trauma Score (RTS) and the New Injury Severity Score (NISS). An artificial patient database of unique patients with trauma (N=82,277) was then generated and used for analysis of the time course modeling and triage classification. Comparative performance analysis of different triage algorithms was performed. In addition, we applied a sophisticated, state-of-the-art clustering method using the Gower distance to visualize patient cohorts at risk for mistriage. Results The proposed triage algorithm realistically modeled the time course of a patient’s life, depending on injury severity and current vital parameters. Different casualties were ranked by their anticipated time course, reflecting their priority for treatment. Regarding the identification of patients at risk for mistriage, the model outperformed the Simple Triage And Rapid Treatment’s triage algorithm but also exclusive stratification by the RTS or the NISS. Multidimensional analysis separated patients with similar patterns of injuries and vital parameters into clusters with different triage classifications. In this large-scale analysis, our algorithm confirmed the previously mentioned conclusions during simulation and descriptive analysis and underlined the significance of this novel approach to triage. Conclusions The findings of this study suggest the feasibility and relevance of our model, which is unique in terms of its ranking system, prognosis outline, and time course anticipation. The proposed triage-ranking algorithm could offer an innovative triage method with a wide range of applications in prehospital, disaster, and emergency medicine, as well as simulation and research.
Targeting MYC in combination with epigenetic regulators induces synergistic anti-leukemic effects in MLLr leukemia and simultaneously improves immunity
2023-05-04

MLL rearranged (MLLr) leukemias are associated with a poor prognosis and a limited response to conventional therapies. Moreover, chemotherapies result in severe side effects with significant impairment of the immune system. Therefore, the identification of novel treatment strategies is mandatory. Recently, we developed a human MLLr leukemia model by inducing chromosomal rearrangements in CD34+ cells using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. This MLLr model authentically mimics patient leukemic cells and can be used as a platform for novel treatment strategies. RNA sequencing of our model revealed MYC as one of the most important key drivers to promote oncogenesis. However, in clinical trials the BRD4 inhibitor JQ-1 leading to indirect blocking of the MYC pathway shows only modest activity. We and others previously reported that epigenetic drugs targeting MAT2A or PRMT5 promote cell death in MLLr cells. Therefore, we use these drugs in combination with JQ-1 leading to augmented anti-leukemic effects. Moreover, we found activation of T, NK and iNKT cells, release of immunomodulatory cytokines and downregulation of the PD-1/PD-L1 axis upon inhibitor treatment leading to improved cytotoxicity. In summary, the inhibition of MYC and MAT2A or PRMT5 drives robust synergistic anti-leukemic activity in MLLr leukemia. Moreover, the immune system is concomitantly activated upon combinatorial inhibitor treatment, hereby further augmenting the therapeutic efficiency.
Diagnostic value of anti-Müllerian hormone combined with androgen-levels in Chinese patients with polycystic ovary syndrome
2023-05-04

The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.
Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation
2023-05-04

Abstract Psoriasis is an immune‐mediated inflammatory skin disease driven by interleukin‐17A (IL‐17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL‐17A overexpression (K14‐IL‐17A ind/+ , IL‐17A ind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin‐/luminol‐based assays, respectively. Quantitative RT‐PCR determined neutrophilic activity and inflammation‐related markers in skin and aorta. To track skin‐derived immune cells, we used PhAM‐K14‐IL‐17A ind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14‐IL‐17A ind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9 ) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature‐invading neutrophils must originate directly from the bone marrow. Hence, the skin‐vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients.
Quasibound states of analytic black-hole configurations in three and four dimensions
2023-05-04

In this work we analyze the sound perturbation of Unruh's acoustic effective geometry in both (2+1) and (3+1) spacetime dimensions and present an exact analytical expression for the quasibound states of these idealized black-hole configurations by using a new approach recently developed, which uses the polynomial conditions of the hypergeometric functions. Our main goal is to discuss the effects of having an event horizon in such effective metrics. We also discuss the stability of the systems and present the radial eigenfunctions related to these quasibound state frequencies. These metrics assume just the form it has for a Schwarzschild black hole near the event horizon, and therefore may, in principle, shed some light into the underlying classical and quantum physics of astrophysical black holes through analog acoustic probes.
Deep Proteogenomics of a Photosynthetic Cyanobacterium
2023-05-05

Cyanobacteria, the evolutionary ancestors of plant chloroplasts, contribute substantially to the Earth's biogeochemical cycles and are of great interest for a sustainable economy. Knowledge of protein expression is the key to understanding cyanobacterial metabolism; however, proteome studies in cyanobacteria are limited and cover only a fraction of the theoretical proteome. Here, we performed a comprehensive proteogenomic analysis of the model cyanobacterium <i>Synechocystis</i> sp. PCC 6803 to characterize the expressed (phospho)proteome, re-annotate known and discover novel open reading frames (ORFs). By mapping extensive shotgun mass spectrometry proteomics data onto a six-frame translation of the <i>Synechocystis</i> genome, we refined the genomic annotation of 64 ORFs, including eight completely novel ORFs. Our study presents the largest reported (phospho)proteome dataset for a unicellular cyanobacterium, covering the expression of about 80% of the theoretical proteome under various cultivation conditions, such as nitrogen or carbon limitation. We report 568 phosphorylated S/T/Y sites that are present on numerous regulatory proteins, including the transcriptional regulators cyAbrB1 and cyAbrB2. We also catalogue the proteins that have never been detected under laboratory conditions and found that a large portion of them is plasmid-encoded. This dataset will serve as a resource, providing dedicated information on growth condition-dependent protein expression and phosphorylation.
A non-canonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML
2023-05-05

RNA-binding proteins (RBPs) form a large and diverse class of factors many members of which are overexpressed in hematological malignancies. RBPs participate in various processes of mRNA metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in acute myeloid leukemia patients and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells. In AML cells, PIWIL4 binds to a small number of known piwi-interacting RNA. It instead largely interacts with mRNA annotated to protein-coding genic regions and enhancers that are enriched for genes associated with cancer and human myeloid progenitor gene signatures. PIWIL4 depletion in AML cells downregulates human myeloid progenitor signature and LSC-associated genes and upregulates DNA damage signalling. We demonstrate that PIWIL4 is an R-loop resolving enzyme that prevents R-loop accumulation on a subset of AML and LSC-associated genes, and maintains their expression. It also prevents DNA damage, replication stress, and activation of the ATR pathway in AML cells. PIWIL4 depletion potentiates sensitivity to pharmacological inhibition of the ATR pathway and creates a pharmacologically actionable dependency in AML cells.
The Synthesis and Biological Activity of Organotin Complexes with Thio-Schiff Bases Bearing Phenol Fragments
2023-05-05

A number of novel di- and triorganotin(IV) complexes 1–5 (Ph2SnL1, Ph2SnL2, Et2SnL2, Ph3SnL3, Ph3SnL4) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds 1–5 were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes 1 and 2 in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds 4 and 5 with free phenol or catechol fragments are more active in these tests than complexes 1–3 with tridentate O,N,S-coordinated ligands. The effect of compounds 1–5 on the promoted oxidative damage of the DNA by 2,2’-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes 4 and 5 were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds 1–3. The antiproliferative activity of compounds 1–5 was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC50 are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.
Control of inherited structural fabric on the development and exhumation of passive margins – Insights from the Araçuaí Orogen (Brazil)
2023-05-05

The Aracuai Orogen, in eastern Brazil, was formed during the Neoproterozoic - Cambrian amalgamation of West Gondwana. During the Mesozoic - Cenozoic opening of the South Atlantic Ocean , the asso-ciated divergent tectonics, the orogen developed as basement to the passive margin of South America , was progressively covered by thick offshore sedimentary basins, particularly the Espirito Santo, Mucuri, and Cumuruxatiba basins, in which hydrocarbon systems have been exploited. Our understanding of the Aracuai Orogen's passive margin evolution, erosion, and sediment transfer to these basins ultimately depends on constraining the onshore exhumation in response to Mesozoic - Cenozoic events. Here, new and previously published data from apatite fission-track (AFT) analyses and inverse thermal history modelling of (Pre)Cambrian basement rocks from the Aracuai Orogen resolve three discrete basement cooling and associated erosional exhumation episodes. In the Pre-Rift phase, Jurassic - Hauterivian ero-sion of the Aracuai Orogen is most likely related to the adjoining intra-continental West Gondwana flex-ural subsidence, which increased hillslope and river erosion power. In the Rift and Transitional phases, Barremian - Albian accelerated phase of erosion is associated with the uplift of the Atlantic rift shoulders and the establishment of an oceanic base-level. In the Drift phase, reactivations in response to far-field stresses likely triggered a Late Cretaceous - Paleocene rapid erosion event. The rates at which these events unfolded vary spatially and are controlled by inherited structures. The Aracuai Orogen experi-enced slower denudation rates in areas closer to the Sao Francisco Craton, which suggests that the tec-tonic reactivation and related surface uplift during the Mesozoic-Cenozoic is in first-order controlled by lithospheric rigidity. Furthermore, the structural framework of the Paramirim and Pirapora aulacogens and NE-oriented shear zones in the orogen's southeast facilitated later reactivations. From the spatial pat-tern of denudation/exhumation of the Aracuai Orogen during the Mesozoic - Cenozoic, we draw infer-ences on the tectonic development of the offshore basins regarding their hydrocarbon potentials.
Microbially influenced corrosion and rust tubercle formation on sheet piles in freshwater systems
2023-05-05

Abstract The extent of how complex natural microbial communities contribute to metal corrosion is still not fully resolved, especially not for freshwater environments. In order to elucidate the key processes, we investigated rust tubercles forming massively on sheet piles along the river Havel (Germany) applying a complementary set of techniques. In‐situ microsensor profiling revealed steep gradients of O 2 , redox potential and pH within the tubercle. Micro‐computed tomography and scanning electron microscopy showed a multi‐layered inner structure with chambers and channels and various organisms embedded in the mineral matrix. Using Mössbauer spectroscopy we identified typical corrosion products including electrically conductive iron (Fe) minerals. Determination of bacterial gene copy numbers and sequencing of 16S rRNA and 18S rRNA amplicons supported a densely populated tubercle matrix with a phylogenetically and metabolically diverse microbial community. Based on our results and previous models of physic(electro)chemical reactions, we propose here a comprehensive concept of tubercle formation highlighting the crucial reactions and microorganisms involved (such as phototrophs, fermenting bacteria, dissimilatory sulphate and Fe(III) reducers) in metal corrosion in freshwaters.
Long-term Outcome of Asymptomatic Patients With Graft Fibrosis in Protocol Biopsies After Pediatric Liver Transplantation
2023-05-05

Background. The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood. Methods. We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT. Results. In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently ( P = 0.027). Conclusions. At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care.