julilili42/papers huggingface dataset:
Getting the Best out of Capillary Electrophoresis and Capillary Electrophoresis–Mass Spectrometry by Quantifying Sources of Peak Broadening for Proteins Using Polyelectrolyte Multilayer Coated Fused Silica Capillaries
2024-09-10

Capillary electrophoresis (CE) has emerged as a relevant technique for protein and biopharmaceutical analysis, as it combines high separation efficiency, sensitivity, and versatility. The use of capillary coatings, including successive multiple ionic-polymer layers (SMILs), reduces interactions between analytes and the capillary, further improving the CE performance. Nevertheless, separations done on SMIL coatings rarely surpass 500 × 10<sup>3</sup> plates/m. To obtain the best out of the CE, it is interesting to have a detailed look at the sources of peak dispersion. Separations of a mix of model proteins were performed on (poly(diallyldimethylammonium chloride)/poly(styrenesulfonate))<sub>2.5</sub>-coated capillaries at different electrical field strengths, leading to plate height <i>H</i> against migration velocity <i>u</i> plots that enabled a quantitative analysis of each contribution. Using this model, capillary lengths and injected volumes were systematically varied. For the first time, the contribution of sample electrophoretic heterogeneity to the total peak dispersion was deciphered for model proteins and a monoclonal antibody. Dispersion due to electromigration was seen to have an impact on plate heights in the case of triangular peaks of small molecules but not for proteins under the present conditions. UV and mass spectrometry detections were compared on the same capillary, providing valuable information on the impact of the detection type on separation efficiency. Close to 1 million plates/m were reached in the best conditions.
Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron
2024-09-10

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of reactive oxygen species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular reactive oxygen species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment.
Real world experience with the TREO device in standard EVAR: Mid-term results of 150 cases from a German Multicenter study
2024-09-10

Summary: Background: The objective of the study was to analyze mid-term results of unselected patients treated with the TREO (Terumo Aortic, Florida, USA) device at six German hospital sites. Methods: A multicenter, retrospective analysis of patients treated within and outside instructions for use (IFU) from January 2017 to November 2020 was performed. Primary outcomes were technical success, mortality and endograft related complications according to IFU status. Secondary outcomes were aneurysm/procedure related re-interventions. Results: 150 patients (92% male, mean age 73 ±8 years) were treated (within IFU 84% vs. outside IFU 16%) with the TREO device for abdominal aortic aneurysms (n=127 intact, n=17 symptomatic and n=6 ruptured; p=0.30). Technical success was achieved in 147/150 (within IFU 99% vs. outside IFU 92%, p=0.08). 30-day mortality was 2%, one year and overall mortality was 3% and 5%. During a mean follow-up of 28.4 months (range: 1–67.4 months), 35 (25%; within IFU 23% vs. outside IFU 35%, p=0.23) patients suffered from endoleaks. The majority were endoleaks type II (n=33), the remaining type Ia (n=5) and type Ib (n=3). No endoleaks type III-V, migrations or aneurysm ruptures occurred. Overall, 19 patients (13%; within IFU 13% vs. 15% outside IFU, p=0.70) received a secondary intervention: nine endoleak related endovascular procedures, three open conversions, two endograft limb related interventions, four surgical revisions of the femoral access sites and two bowl ischemia related procedures, respectively. Conclusions: This non industry-sponsored, multicenter trial indicates that using the TREO device in a real-world setting (both within and outside IFU) seems feasible in the treatment of patients suffering from AAA. While the rate of complications and secondary interventions is in line with previously published data, the findings highlight the fact that standard EVAR is associated with serious adverse events.
Multisensory perceptual and causal inference is largely preserved in medicated post-acute individuals with schizophrenia
2024-09-10

Hallucinations and perceptual abnormalities in psychosis are thought to arise from imbalanced integration of prior information and sensory inputs. We combined psychophysics, Bayesian modeling, and electroencephalography (EEG) to investigate potential changes in perceptual and causal inference in response to audiovisual flash-beep sequences in medicated individuals with schizophrenia who exhibited limited psychotic symptoms. Seventeen participants with schizophrenia and 23 healthy controls reported either the number of flashes or the number of beeps of audiovisual sequences that varied in their audiovisual numeric disparity across trials. Both groups balanced sensory integration and segregation in line with Bayesian causal inference rather than resorting to simpler heuristics. Both also showed comparable weighting of prior information regarding the signals’ causal structure, although the schizophrenia group slightly overweighted prior information about the number of flashes or beeps. At the neural level, both groups computed Bayesian causal inference through dynamic encoding of independent estimates of the flash and beep counts, followed by estimates that flexibly combine audiovisual inputs. Our results demonstrate that the core neurocomputational mechanisms for audiovisual perceptual and causal inference in number estimation tasks are largely preserved in our limited sample of medicated post-acute individuals with schizophrenia. Future research should explore whether these findings generalize to unmedicated patients with acute psychotic symptoms.
An investigation into differential use of ocher in burials at Khok Phanom Di, Thailand
2024-09-10

Abstract Ocher has been observed as a feature of burial traditions around the world, throughout history and prehistory. In Southeast Asia ocher first appears in Hòabìnhian burials; however, it is used discriminately, varying within and between sites. Understanding the selection process for individuals with pigmented burials has been difficult due to their limited number. The site of Khok Phanom Di, Thailand, dating from ~4000 to 3500 BP, reflects the variation of pigment use seen in earlier sites, with 82% of burials found to have ocher. The cemetery's uninterrupted use for ~500 years, the high number and standard of preservation of human remains, and nearly four decades of bioarcheological research have facilitated a detailed study of the use of pigment in relation to bioarcheological factors. This work examines the relationship between the presence or absence of ocher within a burial and chronology, age, sex, mobility, funerary behavior, and spatial organization to understand whether there was a relationship between selective use of ocher and these attributes. The results found a relationship between ocher use and burial chronology, grave type, grave goods, and age. Multivariate analysis demonstrates that age interacts with the other predictors of ocher. Burials without ocher are almost exclusively those of perinates, these were commonly small, shallow “scoop” burials without grave goods. The presence of ocher in ~38% of perinate burials illustrates the complexity of selective pigment use and demonstrates the need for further research.
Multicomponent Syntheses Enable the Discovery of Novel Quisinostat-Derived Chemotypes as Histone Deacetylase Inhibitors
2024-09-10

Epigenetic drug targets have become an important focus in drug discovery. One of the key mechanisms in epigenetics is the acetylation and deacetylation of histone proteins. In this study, we synthesized and evaluated novel histone deacetylase (HDAC) inhibitors derived from the clinical candidate quisinostat. A library of 16 compounds categorized in three novel chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. The compounds were evaluated for their activity against Plasmodium falciparum, the main malaria parasite, and solid cancer cell lines. The antiplasmodial activity was assessed against P. falciparum strains 3D7 and Dd2, identifying compound 18b of the type C series as the most potent. It demonstrated low nanomolar IC50 values (IC50 (3D7) = 0.023 μM; IC50 (Dd2) = 0.047 μM) and high parasite selectivity (SIMRC-5/Pf3D7 &gt; 2174). Docking studies suggested distinct binding modes of 18b with P. falciparum and human HDAC1. The in vitro anticancer activity was also evaluated in the Cal27 and HepG2 cell lines and compounds 9b, 9d, and 13f showed potent antiproliferative activity. Compound 9d significantly induced caspase 3/7-mediated apoptosis and caused hyperacetylation of histone H3 and α-tubulin, indicating robust cellular target engagement. Overall, in this work we have identified several promising HDAC inhibitors with antimalarial and anticancer activities, providing valuable leads for further drug development efforts aimed at creating derivatives with reduced cytotoxicity compared to quisinostat.
Continuous Tuning of Intersystem Crossing Times in Rose Bengal Water/Methanol Solutions
2024-09-10

We use femtosecond transient broadband absorption spectroscopy (TAS) to characterize rose bengal in water/methanol solutions and reveal a continuous tunability of intersystem crossing (ISC) times by changing the mole fraction of the solvents. We find that the transients of excited state absorptions (ESA) in rose bengal at ~430 nm can be attributed to transitions from the singlet state S1, with decay times of 74 ps via ISC in pure water and up to 405 ps in pure methanol. TA measurements at near-infrared wavelengths on the other hand reveal the rise of an ESA at ~1080 nm from the triplet state T1 with time constants of 68 ps and 491 ps in pure water and methanol respectively, strongly supporting the associated UV-Vis TAS data. Solvent mixtures show a quasi-linear rise of the ISC times with increasing mole fractions of methanol and indicate that rose bengal in varying solvent mixtures can be used as a model system to study their influence on excited state photophysics.
Bridging classrooms and technology: Supporting teaching practice with an LLM-powered ICALL system
2024-09-10

Recent years have witnessed the rapid advancement of Artificial Intelligence (AI) technologies, holding immense potential for revolutionising learning and teaching in the realm of Intelligent Computer-Assisted Language Learning (ICALL). However, most ICALL systems tend to prioritize learners’ perspectives over those of teachers, whose involvement is crucial for integrating these systems in real-life school contexts. This oversight often results in teachers' reluctance to adopt and introduce these systems in daily teaching, thereby limiting their potential use in schools and reducing the ecological validity of research findings in actual language learning environments. This article aims to illustrate the ICALL system “ARES” to support teachers in their daily teaching practice with the power of a Large Language Model (LLM) with cooperating teachers’ knowledge, enabling full integration into real-life school education. Aiming to foster the teachers’ use of ICALL systems in real-life English as a Foreign/Second Language (EFL/ESL) settings, the design and development of the system have employed a cooperative approach with educators to optimize its responsiveness to user needs. In this article, we specifically present features designed to support teachers in their daily teaching practice and outline further evaluation of the system via questionnaires and log data.
Histones and histone variant families in prokaryotes
2024-09-11

Abstract Histones are important chromatin-organizing proteins in eukaryotes and archaea. They form superhelical structures around which DNA is wrapped. Recent studies have shown that some archaea and bacteria contain alternative histones that exhibit different DNA binding properties, in addition to highly divergent sequences. However, the vast majority of these histones are identified in metagenomes and thus are difficult to study in vivo. The recent revolutionary breakthroughs in computational protein structure prediction by AlphaFold2 and RoseTTAfold allow for unprecedented insights into the potential function and structure of previously uncharacterized proteins. Here, we categorize the prokaryotic histone space into 17 distinct groups based on AlphaFold2 predictions. We identify a superfamily of histones, termed α 3 histones, which are common in archaea and present in several bacteria. Importantly, we establish the existence of a large family of histones throughout archaea and in some bacteriophages that, instead of wrapping DNA, bridge DNA, thereby diverging from conventional nucleosomal histones.
Physioxia rewires mitochondrial complex composition to protect stem cell viability
2024-09-11

Human induced pluripotent stem cells (hiPSCs) are an invaluable tool to study molecular mechanisms on a human background. Culturing stem cells at an oxygen level different from their microenvironmental niche impacts their viability. To understand this mechanistically, dermal skin fibroblasts of 52 probands were reprogrammed into hiPSCs, followed by either hyperoxic (20 % O<sub>2</sub>) or physioxic (5 % O<sub>2</sub>) culture and proteomic profiling. Analysis of chromosomal stability by Giemsa-banding revealed that physioxic -cultured hiPSC clones exhibited less pathological karyotypes than hyperoxic (e.g. 6 % vs. 32 % mosaicism), higher pluripotency as evidenced by higher Stage-Specific Embryonic Antigen 3 positivity, higher glucose consumption and lactate production. Global proteomic analysis demonstrated lower abundance of several subunits of NADH:ubiquinone oxidoreductase (complex I) and an underrepresentation of pathways linked to oxidative phosphorylation and cellular senescence. Accordingly, release of the pro-senescent factor IGFBP3 and β-galactosidase staining were lower in physioxic hiPSCs. RNA- and ATAC-seq profiling revealed a distinct hypoxic transcription factor-binding footprint, amongst others higher expression of the HIF1α-regulated target NDUFA4L2 along with increased chromatin accessibility of the NDUFA4L2 gene locus. While mitochondrial DNA content did not differ between groups, physioxic hiPSCs revealed lower polarized mitochondrial membrane potential, altered mitochondrial network appearance and reduced basal respiration and electron transfer capacity. Blue-native polyacrylamide gel electrophoresis coupled to mass spectrometry of the mitochondrial complexes detected higher abundance of NDUFA4L2 and ATP5IF1 and loss of incorporation into complex IV or V, respectively. Taken together, physioxic culture of hiPSCs improved chromosomal stability, which was associated with downregulation of oxidative phosphorylation and senescence and extensive re-wiring of mitochondrial complex composition.
The Replication Database: Documenting the Replicability of Psychological Science
2024-09-11

In psychological science, replicability—repeating a study with a new sample achieving consistent results (Parsons et al., 2022)—is critical for affirming the validity of scientific findings. Despite its importance, replication efforts are few and far between in psychological science with many attempts failing to corroborate past findings. This scarcity, compounded by the difficulty in accessing replication data, jeopardizes the efficient allocation of research resources and impedes scientific advancement. Addressing this crucial gap, we present the Replication Database (https://forrt-replications.shinyapps.io/fred_explorer), a novel platform hosting 1,239 original findings paired with replication findings. The infrastructure of this database allows researchers to submit, access, and engage with replication findings. The database makes replications visible, easily findable via a graphical user interface, and tracks replication rates across various factors, such as publication year or journal. This will facilitate future efforts to evaluate the robustness of psychological research.
Multimodal assessment of the role of intolerance of uncertainty in fear acquisition and extinction
2024-09-11

Personality traits linked to internalizing disorders influence the way we develop fears, but also how we regain a sense of safety. In the present study, we investigated the effect of intolerance of uncertainty (IU) on defensive responses using a differential fear conditioning protocol with an extinction phase. The conditioned stimulus was associated with an aversive sound (90 dB) in 75 % of the presentations during acquisition. A final sample of 176 participants completed the experiment. We measured self-reports of associative (expectancy of the unconditioned stimulus in acquisition) and evaluative learning (arousal and valence), and both physiological (skin conductance response) and electrocortical responses (steady-state visually evoked potentials, ssVEPs; late positive potentials, LPP) to the conditioned stimuli. Our results show that IU's impact is limited, with no effect in both acquisition and extinction. These findings emphasize the necessity of large samples in research on inter-individual differences and contribute to our understanding of how IU may or may not be involved in fear and safety learning processes considering multiple aspects of fear responding.
Learning and transfer of response–effect relations
2024-09-11

Acting means changing the environment according to one’s own goals, and this often requires bodily movements as responses. How these responses are selected is a central question in contemporary cognitive psychology. The ideomotor principle offers a simple answer based on two assumptions: An agent first learns an association between a response and its effects. Later, this association can be used in a reverse way: When the agent wants to achieve a desired effect and activates its representation, the associated response representation becomes activated as well. This reversed use of the learned association is considered the means to select the required response. In three experiments, we addressed two questions related to the first assumption: First, we tested whether effect representations generalise to more abstract conceptual knowledge. This is important, because outside the laboratory and in novel situations, effects are variable and not always exactly identical, such that generalisation is necessary for successful actions. Second, the nature of the response–effect relation has been debated recently, and more data are necessary to put theorising on firm empirical ground. Results of our experiments suggest that (a) abstraction to conceptual knowledge seems to occur only under very restricted situations, and (b) it seems that no (implicit) associations between responses and effects are learned, but rather (explicit) propositional knowledge in the form of rules.
“Anything that would help is a positive development”: feasibility, tolerability, and user experience of smartphone-based digital phenotyping for people with and without type 2 diabetes
2024-09-11

Abstract Background Digital phenotyping, the in-situ collection of passive (phone sensor) and active (daily surveys) data using a digital device, may provide new insights into the complex relationship between daily behaviour and mood for people with type 2 diabetes. However, there are critical knowledge gaps regarding its use in people with type 2 diabetes. This study assessed feasibility, tolerability, and user experience of digital phenotyping in people with and without type 2 diabetes after participation in a 2-month digital phenotyping study in Ireland. At study completion, participants rated methodology elements from “not a problem” to a “serious problem” on a 5-point scale and reported their comfort with the potential future use of digital phenotyping in healthcare, with space for qualitative expansion. Results Eighty-two participants completed baseline. Attrition was 18.8%. Missing data ranged from 9–44% depending on data stream. Sixty-eight participants (82.9%) completed the user experience questionnaire (51.5% with type 2 diabetes; 61.8% female; median age-group 50–59). Tolerability of digital phenotyping was high, with “not a problem” being selected 76.5%—89.7% of the time across questions. People with type 2 diabetes (93.9%) were significantly more likely to be comfortable with their future healthcare provider having access to their digital phenotyping data than those without (53.1%), χ2 (1) = 14.01, p = &lt; .001. Free text responses reflected a range of positive and negative experiences with the study methodology. Conclusions An uncompensated, 2-month digital phenotyping study was feasible among people with and without diabetes, with low attrition and reasonable missing data rates. Participants found digital phenotyping to be acceptable, and even enjoyable. The potential benefits of digital phenotyping for healthcare may be more apparent to people with type 2 diabetes than the general population.