julilili42/papers huggingface dataset:
Self-generating autocatalytic networks: structural results, algorithms, and their relevance to evolutionary processes
2023-09-04

Abstract The concept of an autocatalytic network of reactions that can form and persist, starting from just an available food source, has been formalised by the notion of a Reflexively-Autocatalytic and Food generated (RAF) set. The theory and algorithmic results concerning RAFs have been applied to a range of settings, from metabolic questions arising at the origin of life, to ecological networks, and cognitive models in cultural evolution. In this paper, we present new structural and algorithmic results concerning RAF sets, by studying more complex modes of catalysis that allow certain reactions to require multiple catalysts (or to not require catalysis at all), and discuss the differing ways catalysis has been viewed in the literature. We then focus on the structure and analysis of minimal RAFs, and derive structural results and polynomial-time algorithms, with applications to metabolic network data described briefly.
Breaking with Traditions? How Parental Separation Affects Adolescents’ Gender Ideologies in the UK
2023-09-04

In the context of increasing deinstitutionalisation of family relationships, this study assesses the argument that parental union dissolution leads to more egalitarian gender ideologies among children, thereby promoting the gender revolution. Integrating a sociological understanding of gender as social structure with social-cognitive theory of gender development, we investigate whether any effect of parental union dissolution can be explained by parents restructuring work and care responsibilities along more egalitarian lines after separation. Although parental separation is an increasingly common experience, gender socialisation research has focused on biological two-parent families. Evidence on variations in gender ideologies by family structures is scant and based mostly on cross-sectional data from US.Drawing on longitudinal data from the UK Millennium Cohort Study, this study applied fixed-effects panel models to estimate the effects of parental union dissolution on gender ideologies of 6,577 adolescents between ages 11 and 14. Parental separation is found to result in more egalitarian gender ideologies toward female employment among boys but not among girls. In line with the role restructuring argument, the positive effect of separation on egalitarianism is driven by boys who maintain frequent contact with their nonresident fathers and whose fathers had rarely had full responsibility for childcare before separation.
1 Preliminaries
2023-09-04

As a commodity, paper reached Europe in the 12 th century through the Arab merchants who traversed North Africa. 1 Like parchment, this early paper was very fragile, as it was made with plant-based resins that gave it little sturdiness.Over the following two centuries, manufacturing technologies and paper workshops appeared in Europe, where animal-based glues and more evolved tools were used in paper production.The gradual replacement of wool with flax brought greater strength to the final product and allowed paper to last longer.One of the centers of paper manufacture was Genoa, where many printing presses were then set up, owing to the availability of paper.As a marking technique, stamping was developed quite early in human history.On the Mediterranean coasts, the process of applying engraved brass plates to tanned animal skins, to obtain ornamental motifs, was transferred to making covers for manuscript codices. 2 In the 14 th century, Europe saw the coming of imprinted cloths from East Asia, made by pressing colored inks onto the textiles with wood or metal tools. 3 Towards the middle of the 14 th century, Middle Eastern and subsequently European printing technology had reached the phase of xylographs or block prints: wooden plates engraved with sacred words, biblical scenes, images of saints, or brief moralizing texts, were inked, sometimes in color, and then pressed on to paper or pieces of cloth. 4 Block-prints are also preserved that comprise texts in Arabic script, not dated but, in some cases, datable approximately to the 11 th or even the 10 th century by archeological or radio-carbon 1 For the history of paper production and the import from the Far East (China) to Europe via Transoxiana and Baghdad, see Beatrice Gruendler, The Rise of the Arabic Book, Cambridge, MA and London, 2020, p. 103-104. 2 In ancient Egypt, the imprinting procedure generated the art of the tattoo, also using wooden matrices, some preserved to this day in museums around the world.3 On the emerging knowledge of the 'typographic principle' in the West as early as the 13 th century, because of the commercial connections between Eastern Asia and Europe, see Olivier Deloignon, "L'invention d'imprimer par poinçons et caractères", in Nathalie Coilly and Caroline
The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique
2023-09-05

Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt “spinal cord” dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.
Treatment of aseptic facial granuloma as a manifestation of pediatric rosacea with oral macrolides
2023-09-05

Abstract Aseptic facial granuloma is a rare pediatric disease, presenting with asymptomatic facial nodules on the cheeks or the eyelids and may represent a form of granulomatous rosacea in children. In this retrospective case series, 12 children with aseptic facial granuloma were treated with oral macrolides (erythromycin or roxithromycin) resulting in a healing of the lesions within a mean treatment time of 5.25 months with no recurrences. The treatment was mainly well tolerated. Oral macrolides may be effective in the treatment of patients with aseptic facial granuloma.
A SAS Macro for Automated Stopping of Markov Chain Monte Carlo Estimation in Bayesian Modeling with PROC MCMC
2023-09-05

A crucial challenge in Bayesian modeling using Markov chain Monte Carlo (MCMC) estimation is to diagnose the convergence of the chains so that the draws can be expected to closely approximate the posterior distribution on which inference is based. A close approximation guarantees that the MCMC error exhibits only a negligible impact on model estimates and inferences. However, determining whether convergence has been achieved can often be challenging and cumbersome when relying solely on inspecting the trace plots of the chain(s) or manually checking the stopping criteria. In this article, we present a SAS macro called %automcmc that is based on PROC MCMC and that automatically continues to add draws until a user-specified stopping criterion (i.e., a certain potential scale reduction and/or a certain effective sample size) is reached for the chain(s).
Automated Intracranial Clot Detection: A Promising Tool for Vascular Occlusion Detection in Non-Enhanced CT
2023-09-05

(1) Background: to test the diagnostic performance of a fully convolutional neural network-based software prototype for clot detection in intracranial arteries using non-enhanced computed tomography (NECT) imaging data. (2) Methods: we retrospectively identified 85 patients with stroke imaging and one intracranial vessel occlusion. An automated clot detection prototype computed clot location, clot length, and clot volume in NECT scans. Clot detection rates were compared to the visual assessment of the hyperdense artery sign by two neuroradiologists. CT angiography (CTA) was used as the ground truth. Additionally, NIHSS, ASPECTS, type of therapy, and TOAST were registered to assess the relationship between clinical parameters, image results, and chosen therapy. (3) Results: the overall detection rate of the software was 66%, while the human readers had lower rates of 46% and 24%, respectively. Clot detection rates of the automated software were best in the proximal middle cerebral artery (MCA) and the intracranial carotid artery (ICA) with 88–92% followed by the more distal MCA and basilar artery with 67–69%. There was a high correlation between greater clot length and interventional thrombectomy and between smaller clot length and rather conservative treatment. (4) Conclusions: the automated clot detection prototype has the potential to detect intracranial arterial thromboembolism in NECT images, particularly in the ICA and MCA. Thus, it could support radiologists in emergency settings to speed up the diagnosis of acute ischemic stroke, especially in settings where CTA is not available.
Influence of Backbone Ladderization and Side Chain Variation on the Orientation of Diketopyrrolopyrrole-Based Donor-Acceptor Copolymers
2023-09-05

Ladder polymers with poly(diketopyrrolopyrrole) (DPP) moieties have recently attracted enormous interest for a large variety of opto-electronic applications. Since the rigidity of the backbone increases with ladderization, a strong influence on the self-organization of thin films is expected. We study the molecular orientation of DPP-based ladder polymers in about 50 nm thin films using polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS). Exemplarily, for one polymer, the orientation in thicker films is qualitatively investigated by infrared spectroscopy in transmission. Further, this method allows us to rule out the effects of a possible azimuthal ordering, which would affect the analysis of the orientation by PM-IRRAS. For all polymers, the long axis of the polymer backbone is preferentially oriented parallel to the substrate surface, pointing to a high degree of ordering. It is suggested that the choice of the side chains might be a promising way to tune for face-on and edge-on orientations. The exemplarily performed investigation of interface properties on substrates with different work functions suggests that the choice of the side chains has a minor effect on the interfacial electronic interface structure.
An atypical endomembrane localized CNL-type immune receptor with a conserved deletion in the N-terminal signaling domain functions in cell death and immunity
2023-09-05

ABSTRACT Plants have evolved intracellular nucleotide-binding leucine rich repeat receptors (NLRs) to induce a superior immune response. Upon activation, coiled-coil (CC) domain containing NLRs (CNLs) oligomerize to form apparent cation channels that promote calcium influx and cell death induction, with the alpha-1 helix of the individual CC domains penetrating membranes. Some members of a monophyletic subclass of CNLs, the ancient and autonomous NLRs (ANLs), are characterized by putative N- myristoylation and S-acylation sites at the N-terminus of their CC G10/GA domain, potentially mediating permanent membrane association. Whether these P otentially M embrane L ocalized NLRs (PMLs) mediate cell death upon activation in a similar way as reported for other CNLs has been unknown. We integrated phylogenetic, cell- biological, and functional studies to uncover the cell death function of an atypical but conserved Arabidopsis PML, PML5, which has a 113 amino acid deletion in its CC G10/GA domain. Active PML5 oligomers localize in Golgi membranes and the tonoplast, changes vacuolar morphology, and induce cell death, with the short N- terminus being sufficient for cell death. Mutant analysis supports a potential key role of PMLs in plant immunity. Similar deletions as in Arabidopsis PML5 are found in several Brassicales paralogs, pointing to the evolutionary importance of this innovation. PML5 is thus a naturally occurring CNL variant with a minimal signaling ‘domain’ and its further study should help in understanding the functional importance of this minimal domain for NLR signaling.
FESSTVaL: The Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg
2023-09-06

Abstract Numerical weather prediction models operate on grid spacings of a few kilometers, where deep convection begins to become resolvable. Around this scale, the emergence of coherent structures in the planetary boundary layer, often hypothesized to be caused by cold pools, forces the transition from shallow to deep convection. Yet, the kilometer-scale range is typically not resolved by standard surface operational measurement networks. The measurement campaign Field Experiment on Submesoscale Spatio-Temporal Variability in Lindenberg (FESSTVaL) aimed at addressing this gap by observing atmospheric variability at the hectometer-to-kilometer scale, with a particular emphasis on cold pools, wind gusts, and coherent patterns in the planetary boundary layer during summer. A unique feature was the distribution of 150 self-developed and low-cost instruments. More specifically, FESSTVaL included dense networks of 80 autonomous cold pool loggers, 19 weather stations, and 83 soil sensor systems, all installed in a rural region of 15-km radius in eastern Germany, as well as self-developed weather stations handed out to citizens. Boundary layer and upper-air observations were provided by eight Doppler lidars and four microwave radiometers distributed at three supersites; water vapor and temperature were also measured by advanced lidar systems and an infrared spectrometer; and rain was observed by a X-band radar. An uncrewed aircraft, multicopters, and a small radiometer network carried out additional measurements during a 4-week period. In this paper, we present FESSTVaL’s measurement strategy and show first observational results including unprecedented highly resolved spatiotemporal cold-pool structures, both in the horizontal as well as in the vertical dimension, associated with overpassing convective systems.
Proteomics elucidating physiological and pathological functions of TDP‐43
2023-09-06

Abstract Trans‐activation response DNA binding protein of 43 kDa (TDP‐43) regulates a great variety of cellular processes in the nucleus and cytosol. In addition, a defined subset of neurodegenerative diseases is characterized by nuclear depletion of TDP‐43 as well as cytosolic mislocalization and aggregation. To perform its diverse functions TDP‐43 can associate with different ribonucleoprotein complexes. Combined with transcriptomics, MS interactome studies have unveiled associations between TDP‐43 and the spliceosome machinery, polysomes and RNA granules. Moreover, the highly dynamic, low‐valency interactions regulated by its low‐complexity domain calls for innovative proximity labeling methodologies. In addition to protein partners, the analysis of post‐translational modifications showed that they may play a role in the nucleocytoplasmic shuttling, RNA binding, liquid‐liquid phase separation and protein aggregation of TDP‐43. Here we review the various TDP‐43 ribonucleoprotein complexes characterized so far, how they contribute to the diverse functions of TDP‐43, and roles of post‐translational modifications. Further understanding of the fluid dynamic properties of TDP‐43 in ribonucleoprotein complexes, RNA granules, and self‐assemblies will advance the understanding of RNA processing in cells and perhaps help to develop novel therapeutic approaches for TDPopathies.
Reliability of gamified reinforcement learning in densely sampled longitudinal assessments
2023-09-06

Reinforcement learning is a core facet of motivation and alterations have been associated with various mental disorders. To build better models of individual learning, repeated measurement of value-based decision-making is crucial. However, the focus on lab-based assessment of reward learning has limited the number of measurements and the test-retest reliability of many decision-related parameters is therefore unknown. In this paper, we present an open-source cross-platform application Influenca that provides a novel reward learning task complemented by ecological momentary assessment (EMA) of current mental and physiological states for repeated assessment over weeks. In this task, players have to identify the most effective medication by integrating reward values with changing probabilities to win (according to random Gaussian walks). Participants can complete up to 31 runs with 150 trials each. To encourage replay, in-game screens provide feedback on the progress. Using an initial validation sample of 384 players (9729 runs), we found that reinforcement learning parameters such as the learning rate and reward sensitivity show poor to fair intra-class correlations (ICC: 0.22–0.53), indicating substantial within- and between-subject variance. Notably, items assessing the psychological state showed comparable ICCs as reinforcement learning parameters. To conclude, our innovative and openly customizable app framework provides a gamified task that optimizes repeated assessments of reward learning to better quantify intra- and inter-individual differences in value-based decision-making over time.
Putative Cancer Stem Cell Markers are Frequently Expressed by Melanoma Cells in Vitro and in Situ but are also Present in Benign Differentiated Cells
2023-09-06

Background: Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours. Methods: We studied a panel of putative CSC surface markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) in 40 established melanoma cell lines and four early-passage melanoma strains by flow cytometry. We additionally examined 40 formalin-fixed paraffin-embedded melanoma tissues using immunofluorescence microscopy. This was compared with their expression in healthy skin, normal differentiated melanocytes and fibroblasts. Results: Most of the putative CSC markers were expressed by both melanoma cell lines and tissues. When present, these proteins were expressed by the majority of cells in the population. However, the expression of these markers by cells in healthy skin sections, normal differentiated melanocytes, and fibroblasts revealed that differentiated non-malignant cells also expressed CSC markers indicating that they lack of specificity for CSCs. Culturing cell lines under conditions more characteristic of the tumour microenvironment upregulated CSC marker expressions in a proportion of cell lines, which correlated with improved cell growth and viability. Conclusions: The testing of melanoma cell lines (n = 40), early-passage cell strains (n = 4), and melanoma tissues (n = 40) showed that several putative CSC markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) are commonly present in a large proportion of melanoma cells in vitro and in situ. Further, we showed that these putative markers lack specificity for CSCs because they are also expressed in differentiated non-malignant cell types (melanocytes, fibroblasts, and skin), which could limit their use as therapeutic targets. These data are consistent with the emerging notion of CSC plasticity and phenotype switching within cancer cell populations.
COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
2023-09-06

Combined BRAF/MEK-inhibition constitutes a relevant treatment option for BRAF-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.
Whole-body modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
2023-09-06

Abstract In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilized whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalized models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.
Functional evaluation allows ACMG/AMP-based re-classification of CNGA3 variants associated with achromatopsia
2023-09-06

Our aequorin-based bioassay allows functionally ensured clinical variant interpretation for 150 CNGA3 missense variants enabling and supporting VUS re-classification and assuring molecular diagnosis to patients affected by CNGA3-associated achromatopsia, hereby identifying patients eligible for future gene therapy trials on this disease.