julilili42/papers huggingface dataset:
mitoBKCa is functionally expressed in murine and human breast cancer cells and promotes metabolic reprogramming
2023-12-08

Summary Alterations in the function of K+ channels such as the voltage- and Ca2+ activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with cell permeable BKCa channel blocker, we show that mitoBKCa modulates overall cellular and mitochondrial energy production and mediates the metabolic rewiring referred to as the “Warburg effect”, thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCa and BKCa transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCa, combined with established anti-cancer approaches, could represent a novel treatment strategy for selected BC patients.
Rainfall redistribution in subtropical Chinese forests changes over 22 years
2023-12-08

Abstract. Rainfall redistribution through the vegetation canopy plays a key role in the hydrological cycle. Although there have been studies on the heterogeneous patterns of rainfall redistribution in some ecosystems, the understanding of this process in different stages of forest succession remains insufficient. Therefore, this study investigated the change tendency of rainfall redistribution and rainwater chemistry in a subtropical succession forest area in South China, based on 22 years (2001–2022) of monitoring 740 valid rainfall events. Results showed that at the event scale throughfall ratio showed in order broadleaf forest (BF) &lt; mixed forest (MF) &lt; pine forest (PF), and stemflow ratio showed in order BF &gt; MF &gt; PF. At the interannual scale, annual gross rainfall considerably shifted over time, which directly induced the variable accumulation of annual throughfall and annual stemflow. In the last 22 years, annual variability of throughfall presented in order MF (CV, 9.7 %) &lt; BF (15.6 %) &lt; PF (16.1 %), and annual variability of stemflow presented in order MF (CV, 38.6 %) &lt; PF (50.9) &lt; BF (56.2 %). The spatial variability of stemflow was always greater than that of throughfall. Besides, the difference of rainwater chemistry fluxes (TN, TP and K+) among the three forest types were found and they changed over time. Throughfall was characterized with high chemistry fluxes compared to open rainfall followed by stemflow. On average, TN and TP fluxes of throughfall presented in order BF &lt; MF &lt; PF, while K+ flux of throughfall presented in order BF &gt; MF &gt; PF. The above results indicated that the patterns of rainfall redistribution often changed over time. The event-scale accumulation of throughfall and stemflow potentially induced the interannual-scale variability. Both water volume and chemistry of throughfall and stemflow depended on the effect of rainfall and forest factors. This study provided insight into the rainfall redistribution process by linking the long-term changing of rainfall pattern and subtropical forest succession sequence.
Performance Differences of a Touch-Based Serial Reaction Time Task in Healthy Older Participants and Older Participants With Cognitive Impairment on a Tablet: Experimental Study
2023-12-08

Background Digital neuropsychological tools for diagnosing neurodegenerative diseases in the older population are becoming more relevant and widely adopted because of their diagnostic capabilities. In this context, explicit memory is mainly examined. The assessment of implicit memory occurs to a lesser extent. A common measure for this assessment is the serial reaction time task (SRTT). Objective This study aims to develop and empirically test a digital tablet–based SRTT in older participants with cognitive impairment (CoI) and healthy control (HC) participants. On the basis of the parameters of response accuracy, reaction time, and learning curve, we measure implicit learning and compare the HC and CoI groups. Methods A total of 45 individuals (n=27, 60% HCs and n=18, 40% participants with CoI—diagnosed by an interdisciplinary team) completed a tablet-based SRTT. They were presented with 4 blocks of stimuli in sequence and a fifth block that consisted of stimuli appearing in random order. Statistical and machine learning modeling approaches were used to investigate how healthy individuals and individuals with CoI differed in their task performance and implicit learning. Results Linear mixed-effects models showed that individuals with CoI had significantly higher error rates (b=−3.64, SE 0.86; z=−4.25; P&lt;.001); higher reaction times (F1,41=22.32; P&lt;.001); and lower implicit learning, measured via the response increase between sequence blocks and the random block (β=−0.34; SE 0.12; t=−2.81; P=.007). Furthermore, machine learning models based on these findings were able to reliably and accurately predict whether an individual was in the HC or CoI group, with an average prediction accuracy of 77.13% (95% CI 74.67%-81.33%). Conclusions Our results showed that the HC and CoI groups differed substantially in their performance in the SRTT. This highlights the promising potential of implicit learning paradigms in the detection of CoI. The short testing paradigm based on these results is easy to use in clinical practice.
Filamin protects myofibrils from contractile damage through changes in its mechanosensory region
2023-12-08

Abstract Filamins are mechanosensitive actin crosslinking proteins that organize the actin cytoskeleton in a variety of shapes and tissues. In muscles, filamin crosslinks actin filaments from opposing sarcomeres, the smallest contractile units of muscles. This happens at the Z-disc, the actin-organizing center of sarcomeres. In flies and vertebrates, filamin mutations lead to fragile muscles that appear ruptured, suggesting filamin helps counteract muscle rupturing during muscle contractions either by providing elastic support or through signaling. The mechanistic details of filamin in this process are largely unknown. Here we use the indirect flight muscles of Drosophila to interrogate the molecular details by which filamin provides cohesion to the Z-disc. We made novel filamin mutations affecting the C-terminal region and detected two Z-disc phenotypes: dissociation of actin filamins and Z-disc rupture. We focused on the ruptured defect and tested a constitutively closed filamin mutant, which results in ruptured Z-discs, and a constitutively open mutant which gives rise to enlarged Z-discs. Finally, we show that muscle contraction is required for Z-disc rupture. We therefore propose that filamin senses myofibril damage by elastic changes in its mechanosensory region, which induces myofibril repair.
Entering the Prophetic Realm: ʿAbd Rabbihī ibn Sulaymān al-Qaliyūbī (d. 1968) on the Nature of Mediation (tawassul)
2023-12-08

In his comprehensive work Fayḍ al-wahhāb, ʿAbd Rabbihī ibn Sulaymān al-Qaliyūbī (d. 1968) extensively explores the Prophet Muhammad’s role in theology and argues against interpretations influenced by Wahhābī thought. He emphasizes the prophetic realm, or prophecy and its traces, particularly the means by which believers can establish a connection with it. This article pays special attention to al-Qaliyūbī’s understanding of mediation (tawassul); that is, how the Prophet—by virtue of his elevated status, ordained by God—can serve as a means; similar to how a ritual prayer or any good deed ultimately serves as a means to draw closer to God. For al-Qaliyūbī, following the Prophet means not only regarding him as the founder of the religion, but also incorporating his spirit and character into one’s own life. This article proceeds in four steps: (1) It addresses the systematics of prophecy concerning practical ethics and how this realm can be entered; (2) It introduces the three-layered paradigm of later theology and al-Qaliyūbī’s work; (3) It explores the topic of what constitutes a means (wasīla) and the theological implications of using a means in prayer (tawassul); (4) It zooms in on the aspect of what qualifies a means to be used in an individual prayer.
Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2
2023-12-08

Abstract Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation – or lack thereof – of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the “epigenetic toolkit” available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with C. elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus . However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to enable reverse-genetic experiments related to plasticity, and in doing so have described the first loss of PRC2 in a multicellular organism.
Pulsar-wind-nebula-powered Galactic center X-ray filament G0.13-0.11: Proof of the synchrotron nature by IXPE
2023-12-08

We report the discovery of X-ray polarization from the X-ray-bright filament. G0.13-0.11 in the Galactic center (GC) region. This filament features a bright, hard X-ray source that is most plausibly a pulsar wind nebula (PWN) and an extended and structured diffuse component. Combining the polarization signal from IXPE with the imaging/spectroscopic data from Chandra, we find that X-ray emission of G0.13-0.11 is highly polarized PD= % in the 3-6 keV band, while the polarization angle is PA= . This high degree of polarization proves the synchrotron origin of the X-ray emission from G0.13-0.11. In turn, the measured polarization angle implies that the X-ray emission is polarized approximately perpendicular to a sequence of nonthermal radio filaments that may be part of the GC Radio Arc. The magnetic field on the order of appears to be preferentially ordered along the filaments. The above field strength is the fiducial value that makes our model self-consistent, while the other conclusions are largely model independent.
“Per aspera ad astra”: Starry Heavens and Sidereal Metamorphosis in Jesuit Emblematics
2023-12-08

Abstract This article sheds new light on a series of Jesuit emblems, from both spiritual and cosmological perspectives, in which stars and starlit night skies figure prominently. The starting point is Ignatius of Loyola’s preferred devotional exercise, as Pedro Ribadeneyra recounts: the contemplation of stars. Given Ignatius’s importance in this exercise, they are recurring motifs in Jesuit emblematics. Considering this exercise in the context of the classical definition of human beings as contemplators of heaven, I will provide an interpretive framework based on anthropology, epistemology, and ethics. I argue that stellar imagery draws on three closely intertwined key elements: firstly, the idea that God reveals himself through nature. Secondly, that knowledge of God is mediated by sight but achieved by reason, and finally, that the divine nature of stars and heavenly bodies made them worthy models to ponder and imitate. Stars mediate access to the knowledge of God and, as a poetic metaphor for deification, provide a model for cultivating one’s soul and conforming it to the divine. This article is part of the special issue of the Journal of Jesuit Studies on Jesuit emblems and emblematic edited by Walter S. Melion.
Anyskop Blowout Prehistoric Dataset, Western Cape, South Africa
2023-12-08

These Stone Age archaeological datasets were collected in 2001 and 2002 by a team from the Department of Early Prehistory and Quaternary Ecology of the University of Tübingen (Germany) headed by Nicholas J. Conard. Many South African researchers collaborated on this project, with Pippa Haarhoff, John Compton, Dave Roberts, and Stephan Woodborne deserving special mention. The field work took place at the Anyskop Blowout (ANY1) located within the West Coast Fossil Park near Langebaanweg, Western Cape, South Africa. The field work was conducted with the help of students from the universities of Tübingen and Cape Town. The datasets are predominantly in English (with some German as well) and include field data in the MAIN table. Further analytical data for many classes of artifacts include: LITHICS, FAUNA, POTTERY, MODERN, BUCKETS, REFITS. All collected materials are curated by the Iziko South African Museums in Cape Town under accession numbers SAM-AA-8903 (finds collected by other teams before 2001) and SAM-AA-9007 (finds from this study, 2001-2002). Some of the finds are exhibited in the museum at the West Coast Fossil Park. Funding for this research project came mainly from the German Research Foundation (DFG - CO 226/5-1, 5-2, 5-5 and 5-6) and the University of Tübingen. Significant support was provided by the Iziko South African Museums, the West Coast Fossil Park, and the University of Cape Town.
Sulfate affinity controls phosphate sorption and the proto-transformation of schwertmannite
2023-12-08

Schwertmannite is a metastable sulfate-rich ferric iron Fe(III) (oxyhydr)oxide and a common mineral in acid mine drainage sites and acid sulfate soils. Schwertmannite is also used as a sorbent in various industrial applications, including phosphate removal for water treatment and environmental remediation. Phosphate sorption to schwertmannite, however, is complex and likely involves ligand exchange for inner- and outer-spherically coordinated sulfate groups, both on the surface and in the tunnel structure of the mineral. Here, we investigated phosphate sorption, concomitant sulfate release and their impact on the structure of schwertmannite as a function of pH and phosphate concentration. Kinetic and equilibrium batch experiments with synthetic schwertmannite were carried out at pH 3, 6, and 8, and the solid-phase was analyzed using scanning electron microscopy, Mössbauer spectroscopy, infra-red spectroscopy and X-ray diffraction spectroscopy. We found a strong correlation between phosphate sorption and sulfate release, with both following a two-step sorption model. Kinetics of phosphate sorption and sulfate release were faster at more alkaline pH. Maximum phosphate sorption was found at pH 6 (1.7 mmol PO43- g-1) , which decreased to 1.5 and 1.2 mmol PO43- g-1 at pH 3 and 8, respectively. Fourier transform infrared spectroscopy revealed a shift from inner- to outer-spherical coordination of sulfate with increasing pH. 57Mössbauer analyses of schwertmannite indicated a proto-transformation of schwertmannite at neutral to alkaline pH, characterized by a rise in a partially ordered sextet area. This change was interpreted as an increase in crystallinity resulting from the transition from Fe-SO4 to Fe-O domains. This pH-induced proto-transformation was inhibited in the presence of phosphate. We concluded that the phosphate sorption rate and maximum as well as the proto-transformation of schwertmannite were strongly affected by the mineral’s affinity for sulfate. Sorption to schwertmannite should primarily be regarded as a competitive exchange reaction between the sorbing oxyanion and the bound sulfate. This resulted in the highest phosphate sorption at circumneutral pH, a stark contrast to non-sulfate-containing Fe(III) (oxyhydr)oxides, where phosphate sorption is highest at acidic pH. Our results are important for a fundamental understanding of the sorption properties of schwertmannite in phosphate-rich environments as they point towards the central role of sulfate coordination for phosphate immobilization.
Measuring the accuracy of ICA-based artifact removal from TMS-evoked potentials
2023-12-09

As TEP artifacts tend to have small trial-to-trial variability, one should be aware of the possibility of eliminating brain-derived EEG when applying ICA-based cleaning strategies. In practice, after ICA, the artifact component variability can be measured, and it predicts to some extent the cleaning reliability, even when not knowing the clean ground-truth data.
Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged <75 and ≥75 Years: ARCHES Post Hoc Analysis
2023-12-09

Enzalutamide is a drug approved to treat men with prostate cancer. In this report, we compared patients aged <75 and ≥75 yr treated with enzalutamide plus androgen deprivation therapy to determine whether age affected how long they lived without the cancer spreading to other parts of their body. We found that, although younger patients had more favorable survival outcomes, enzalutamide was associated with longer survival and reduced disease spread in both age groups.
Decoding Polarization in a Single Achiral Gold Nanostructure from Emitted Far-Field Radiation
2023-12-10

The emergence of optical chirality in the light emitted from plasmonic nanostructures is commonly associated with their geometrical chirality. Although it has been demonstrated that even achiral structures can exhibit chiral near-fields, the existence of chiroptical far-field responses of such structures is widely neglected. In this paper, we present a detailed analysis of the polarization state in a single planar achiral plasmonic nanostructure that sustains more than one prominent plasmon mode. In consideration of the relative phase, the superposition of the fields associated with these modes determines the polarization state of the emitted light in the far-field. Supported by simulations of the surface charge distribution of the particle, we show that the polarization state of the emitted light is already determined in the near-field. The chiroptical far-field responses are analyzed by polarized single-particle dark-field scattering spectroscopy. We introduce an analytical model that enables us to obtain the polarization information from the spectra of structures with dipolar resonances taken under unpolarized illumination. The same principle is confirmed in polarimetric spectroscopy measurements on rhomboids with systematically varied angles, therefore, introducing increasing values of geometrical chirality to the structures. The agreement between the calculation and measurement demonstrates the general validity of our model for both chiral and achiral structures.
Ice Modeling Indicates Formation Mechanisms of Large-scale Folding in Greenland's Ice Sheet
2023-12-10

Radio-echo sounding (RES) has shown that large-scale folds in the englacial stratigraphy is ubiquitous in Greenland’s ice sheet. However, there is no consensus yet on how these folds form. Here, we use the full-Stokes code Underworld2 to simulate ice movements in three-dimensional convergent flow, mainly investigating the effect of ice anisotropy due to a crystallographic preferred orientation, vertical viscosity and density contrasts in ice layers, and bedrock topography. Our simulated folds show complex patterns and are classified into three types: large-scale folds, small-scale folds and basal-shear folds. The amplitudes of large-scale folds tend to be at their maximum in middle ice layers and decrease towards the surface, in accordance with observations in RES data. We conclude that bedrock topography contributes to perturbations in ice layers, and that ice anisotropy amplifies these into large-scale folds, while vertical viscosity contrasts in ice layers are insufficient for large-scale fold amplification.
Learning to Make Rare and Complex Diagnoses With Generative AI Assistance: Qualitative Study of Popular Large Language Models
2023-12-11

Background Patients with rare and complex diseases often experience delayed diagnoses and misdiagnoses because comprehensive knowledge about these diseases is limited to only a few medical experts. In this context, large language models (LLMs) have emerged as powerful knowledge aggregation tools with applications in clinical decision support and education domains. Objective This study aims to explore the potential of 3 popular LLMs, namely Bard (Google LLC), ChatGPT-3.5 (OpenAI), and GPT-4 (OpenAI), in medical education to enhance the diagnosis of rare and complex diseases while investigating the impact of prompt engineering on their performance. Methods We conducted experiments on publicly available complex and rare cases to achieve these objectives. We implemented various prompt strategies to evaluate the performance of these models using both open-ended and multiple-choice prompts. In addition, we used a majority voting strategy to leverage diverse reasoning paths within language models, aiming to enhance their reliability. Furthermore, we compared their performance with the performance of human respondents and MedAlpaca, a generative LLM specifically designed for medical tasks. Results Notably, all LLMs outperformed the average human consensus and MedAlpaca, with a minimum margin of 5% and 13%, respectively, across all 30 cases from the diagnostic case challenge collection. On the frequently misdiagnosed cases category, Bard tied with MedAlpaca but surpassed the human average consensus by 14%, whereas GPT-4 and ChatGPT-3.5 outperformed MedAlpaca and the human respondents on the moderately often misdiagnosed cases category with minimum accuracy scores of 28% and 11%, respectively. The majority voting strategy, particularly with GPT-4, demonstrated the highest overall score across all cases from the diagnostic complex case collection, surpassing that of other LLMs. On the Medical Information Mart for Intensive Care-III data sets, Bard and GPT-4 achieved the highest diagnostic accuracy scores, with multiple-choice prompts scoring 93%, whereas ChatGPT-3.5 and MedAlpaca scored 73% and 47%, respectively. Furthermore, our results demonstrate that there is no one-size-fits-all prompting approach for improving the performance of LLMs and that a single strategy does not universally apply to all LLMs. Conclusions Our findings shed light on the diagnostic capabilities of LLMs and the challenges associated with identifying an optimal prompting strategy that aligns with each language model’s characteristics and specific task requirements. The significance of prompt engineering is highlighted, providing valuable insights for researchers and practitioners who use these language models for medical training. Furthermore, this study represents a crucial step toward understanding how LLMs can enhance diagnostic reasoning in rare and complex medical cases, paving the way for developing effective educational tools and accurate diagnostic aids to improve patient care and outcomes.