julilili42/papers huggingface dataset:
Evidence against a cortical module for processing communicative gaze
2024-11-21

<title>Abstract</title> Apart from language, our gaze is arguably the most important means of communication. Where we look lets others know what we are interested in and allows them to join our focus of attention. In several studies our group investigated the neuronal basis of gaze following behavior in humans and macaques and described a gaze following patch (GFP) in the posterior temporal cortex as being of central importance for this function. To our knowledge, this makes the GFP the most promising neurobiological correlate of Simon Baron-Cohen’s eye direction detector (EDD), an integral part of his influential mindreading system. With the latter, Baron-Cohen proposed a set of domain-specific neurocognitive modules implementing a functional framework he suggested to be necessary to establish a Theory of Mind - the attribution of mental states to others. The tenet of domain-specificity requires that the EDD processes only and exclusively eye-like stimuli with their typical contrast and movement properties. In this preregistered fMRI study, we aimed to critically test if the GFP fulfills this criterion. Specifically, we tested if it is equivalent to or different from the visual motion processing areas located in the same part of the brain. Contrary to previous studies, the present results clearly demonstrate that GFP activity is not exclusively correlated with the perception of other people’s gaze direction and thus does not fulfill the criterion of domain-specificity. Furthermore, we show that it cannot be functionally dissociated from the MT+ complex, with which it overlaps anatomically. Given that our experiments captured the full extent of gaze-following behavior and were specifically designed to reveal an EED, our results provide evidence against its existence, and therefore against Baron-Cohen's mindreading model as a set of domain-specific modules.
Promising stabs in the Dark: theory virtues and pursuit-worthiness in the Dark Energy problem
2024-11-22

Abstract This paper argues that we ought to conceive of the Dark Energy problem—the question of how to account for observational data, naturally interpreted as accelerated expansion of the universe—as a crisis of underdetermined pursuit-worthiness. Not only are the various approaches to the Dark Energy problem evidentially underdetermined; at present, no compelling reasons single out any of them as more likely to be true than the other. More vexingly for working scientists, none of the approaches stands out as uncontroversially preferable over its rivals in terms of its rationally warranted promise, i.e. the reasons to further work on, explore, and develop it. We demonstrate this claim by applying a Peircean economic model of pursuit-worthiness in terms of a cognitive cost/benefit estimate—with the instantiation of theory virtues as key indicators of cognitive gains—to the four main Dark Energy proposals (the cosmological constant approach, modified gravity, quintessence, and inhomogeneous cosmologies). According to our analysis, these approaches do not admit of an unambiguous, or uncontroversial, ranking with respect to which ansatz deserves distinguished attention and research efforts. The overall methodological counsel that our analysis underwrites recommends a pragmatic double research strategy forward: to encourage and foster theory pluralism and the search for tests—with the goal of enhancing the testability of the CDM model and “testing it to destruction".
Sub-millielectronvolt Line Widths in Polarized Low-Temperature Photoluminescence of 2D PbS Nanoplatelets
2024-11-22

Colloidal semiconductor nanocrystals are promising materials for classical and quantum light sources due to their efficient photoluminescence (PL) and versatile chemistry. While visible emitters are well-established, excellent (near-infrared) sources are still being pursued. We present the first comprehensive analysis of low-temperature PL from two-dimensional (2D) PbS nanoplatelets (NPLs). Ultrathin 2D PbS NPLs exhibit high crystallinity confirmed by scanning transmission electron microscopy, revealing Moiré patterns in overlapping NPLs. At 4 K, unique PL features are observed in single PbS NPLs, including narrow zero-phonon lines with line widths down to 0.6 meV and a linear degree of polarization up to 90%. Time-resolved measurements identify trions as the dominant emission source with a 2.3 ns decay time. Sub-meV spectral diffusion and no inherent blinking over minutes are observed, as well as discrete spectral jumps without memory effects. These findings advance the understanding and underscore the potential of colloidal PbS NPLs for optical and quantum technologies.
Contextualizing predictive minds
2024-11-22

The structure of human memory seems to be optimized for efficient prediction, planning, and behavior. We propose that these capacities rely on a tripartite structure of memory that includes concepts, events, and contexts-three layers that constitute the mental world model. We suggest that the mechanism that critically increases adaptivity and flexibility is the tendency to contextualize. This tendency promotes local, context-encoding abstractions, which focus event- and concept-based planning and inference processes on the task and situation at hand. As a result, cognitive contextualization offers a solution to the frame problem-the need to select relevant features of the environment from the rich stream of sensorimotor signals. We draw evidence for our proposal from developmental psychology and neuroscience. Adopting a computational stance, we present evidence from cognitive modeling research which suggests that context sensitivity is a feature that is critical for maximizing the efficiency of cognitive processes. Finally, we turn to recent deep-learning architectures which independently demonstrate how context-sensitive memory can emerge in a self-organized learning system constrained by cognitively-inspired inductive biases.
Accumulation of alpha-synuclein pathology in the liver exhibits post-translational modifications associated with Parkinson’s disease
2024-11-22

Accumulating evidence demonstrates that alpha-synuclein (α-syn) pathology associated with Parkinson's disease (PD) is not limited to the brain, as it also appears in a select number of peripheral tissues including the liver. In this study, we identified a number of PD-associated α-syn post-translational modifications in the livers of (Thy-1)-h[A30P] mice, a mouse model of familial PD expressing human α-syn harboring the A30P mutation driven by a neuron-specific promoter. <i>Ex vivo</i>, we also demonstrate that human hepatocytes induce post-translational modifications following α-syn fibrillar (PFF) treatment. Moreover, such cells also degrade PFFs over time, whereas oligomeric assemblies are more resistant to degradation, but this process can be enhanced by autophagy stimulators. Collectively, our findings suggest that pathological α-syn is transported to the liver in a modified state or is modified upon arrival, which facilitates its clearance and detoxification, pointing to a role for the liver in the degradation of PD-associated pathology.
MCC: Automated Mass and Charge Curation at Genome-Scale Applied toC. tuberculostearicum
2024-11-22

ABSTRACT Background For many years, antibiotics reliably protected mankind against bacterial infections, including the respiratory tract colonizer Corynebacterium tuberculostearicum . However, the spread of antimicrobial resistance necessitates the search for new treatment options, where the microbiota may play a crucial role. One way to investigate the complex nature of bacteria and their interactions with human hosts or microbiota is through genome-scale metabolic models (GEMs). Constructing GEMs is labor-intensive and time-consuming. Results We introduce the Python package Mass and Charge Curation (MCC), which implements a new automated algorithm to facilitate mass and charge balancing—one of the most time-consuming reconstruction steps. This package manipulates reconstructions by consolidating data from multiple resources and updating the notes -field with relevant changes. It also generates a visual comparison between draft and curated models, ensuring high-quality metabolic reconstructions. Using MCC, we developed a metabolic reconstruction of C. tuberculostearicum strain DSM 44922. The model was improved based on standardization policies, resulting in a functional, well-annotated, high-quality product. We also simulated the organism’s growth in synthetic nasal medium 3 (SNM3). Conclusions The high-quality model i CTUB2024RM consistently resembles growth behavior under realistic conditions in an artificial human nasal environment, enhancing understanding of C. tuberculostearicum and its potential impact on health and disease. The curation process of this model led to the development of the MCC package, which facilitates the mass and charge balancing of arbitrary flux balance constraints (fbc) models in SBML format. Availability MCC is freely available via PIP, from https://github.com/draeger-lab/MassChargeCuration/ . The model i CTUB2024RM can be obtained as an SBML file wrapped in an OMEX archive from BioModels Database, accession MODEL2407310001 . Importance The rise of antibiotic resistance has made it essential to explore alternative treatments for bacterial infections, particularly those caused by respiratory tract colonizers like Corynebacterium tuberculostearicum . Understanding the metabolic behavior of these bacteria and their interactions with the human host or microbiota is crucial. genome-scale metabolic models (GEMs) are powerful tools for investigating these interactions, but they are time-consuming to build. Our new Python package, Mass and Charge Curation (MCC), automates a crucial step in the GEM reconstruction process-mass and charge balancing-making it more efficient and reliable. By applying this tool, we developed a high-quality, functional metabolic model for C. tuberculostearicum ( i CTUB2024RM), which provides deeper insights into the organism’s growth in a simulated human nasal environment. This work offers a foundation for future research into microbial communities and their role in human health.
Violation of auditory regularities is reflected in pupil dynamics
2024-11-22

The brain builds and maintains internal models and uses them to make predictions. When predictions are violated, the current model can either be updated or replaced by a new model. The latter is accompanied by pupil dilation responses (PDRs) related to locus coeruleus activity/norepinephrine release (LC-NE). Following earlier research, we investigated PDRs associated with transitions between regular and random patterns of tones in auditory sequences. We presented these sequences to participants and instructed them to find gaps (to maintain attention). Transitions from regular to random patterns induced PDRs, suggesting that an internal model attuned to the regular pattern is reset. Transitions from one regular pattern to another regular pattern also induced PDRs, suggesting that they also led to a model reset. In contrast, transitions from random patterns to regular patterns did not induce PDRs, suggesting a gradual update of model parameters. We modelled these findings, using pupil response functions to show how ongoing PDRs and pupil event rates were sensitive to the trial-by-trial changes in the information content of the auditory sequences. Expanding on previous research, we suggest that PDRs-as biomarkers for LC-NE activation-may indicate the extent of prediction violations.
Calculating Future 10-Year Breast Cancer Risks in Risk-Adapted Surveillance: A Method Comparison and Application in Clinical Practice
2024-11-22

Abstract The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has successfully implemented risk-adapted breast cancer surveillance for women at high breast cancer risk in Germany. Women with a family history of breast and ovarian cancer but without pathogenic germline variants in recognized breast cancer risk genes are recommended annual breast imaging if their predicted 10-year breast cancer risk is 5% or higher, using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) breast cancer risk model, as outlined in the current GC-HBOC guideline. However, women who initially do not meet this risk threshold may do so later, even if there is no new cancer in their family. To determine when this threshold is crossed, one could annually repeat BOADICEA calculations using an aging pedigree: the “prediction by aging pedigree” (AP) approach. Alternatively, we propose a simplified and more practical “'conditional probability” (CP) approach, which calculates future risks based on the initial BOADICEA assessment. Using data from 6,661 women registered with GC-HBOC, both methods were compared. Initially, 74% of women, ages 30 to 48 years, had a 10-year breast cancer risk below 5%, but 53% exceeded this threshold at an older age based on the AP approach. Among the women with an initial risk below the threshold, the CP approach revealed that 99% of women exceeded the 5% threshold at the same or an earlier age compared with the AP approach (88% of cases were within the same year or 1 year earlier). The CP approach has been implemented as a user-friendly web application. Prevention Relevance: The German Consortium for Hereditary Breast Cancer recommends annual breast imaging for women if their 10-year breast cancer risk is 5% or higher. Women who initially do not meet this risk threshold may do so later. We propose a simple method to determine future risks based on initial risk assessments.
Acute remote ischemic conditioning enhances (CD3+)- but not (FoxP3+)-T-cell invasion in the tumor center and increases IL 17 and TNF-alpha expression in a murine melanoma model
2024-11-22

Introduction Hypoxia can drive tumor progression, suppress anti-tumor immunity, and reduce the effectiveness of radiotherapy and chemotherapy. This study aimed to assess the impact of remote ischemic conditioning (RIC) on tumor oxygenation (sO2) and the anti-tumor immune response. Material and methods Fourteen B16-Ova tumor-bearing C57BL/6N mice received six 5-minute RIC cycles, while another fourteen underwent anesthesia only. Pimonidazole was administered 1.5 hours before sacrifice. Blood flow, sO2, and hemoglobin levels were measured in the non-ischemic hind limb and tumor. Tumor hypoxia was assessed using pimonidazole and CA IX immunohistochemistry, and T cell infiltration by CD3 and FoxP3 staining. Serum levels of 23 cytokines were analyzed using a multiplex immunoassay. Results Isoflurane anesthesia caused a slight intraindividual increase in blood flow (p = 0.07) and sO 2 (p = 0.06) of the hind limb and a sole increase in tumor sO 2 (p = 0.035), whereas RIC improved sO 2 of the tumor in relation to the hind limb (p=0.03). The median of the tumor oxygen saturation reached 51.4% in the control group and 62.7% in the RIC group (p = 0.09), exhibiting a slight tendency towards better oxygenation in the RIC group. Pimonidazole (p=0.24) and CA IX hypoxia score (p=0.48) did not reveal statistically significant differences between the two groups. In RIC-treated tumors, the number of CD3 (p=0.006), but not FoxP3- positive cells (p = 0.84), in the tumor core was significantly higher compared to the control group. In the RIC group, the mean fluorescence intensity (MFI) of IL-17 was significantly higher (p=0.035), and TNF-α was trend-wise higher (p=0.063) compared to the control group. Conclusion Both isoflurane anesthesia and RIC have an impact on microcirculation. The application of RIC counteracted some of the effects of isoflurane, primarily in healthy tissue, and led to a significant improvement in relative tumor tissue oxygenation compared to the non-ischemic hind limb. RIC selectively enhanced immune infiltration within the tumor center, probably by previously activated tumor infiltrating T cells, while having no significant impact on T-regulatory cells. RIC appears to impact the cytokine profile, as indicated by elevated MFIs of TNF-α and IL-17.
European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection
2024-11-23

Abstract Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4, ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I (“ready for clinical use”) classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II (“investigational”) classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.
DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia
2024-11-23

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O2, 48 h) p53 null H358 NSCLC cells after X-ray exposure. We used the colony-forming ability assay to determine cell survival, γH2AX immunofluorescence microscopy to quantify DNA double-strand breaks (DSBs), flow cytometry of DAPI-stained cells to measure cell cycle distribution, ELISAs to quantify IL-6 and IL-8 secretion in cell culture supernatants, and RNA sequencing to determine gene expression. Chronic hypoxia increased the colony-forming ability and radioresistance of H358 cells. It did not affect the formation or resolution of X-ray-induced DSBs. It reduced the fraction of cells undergoing G2 arrest after X-ray exposure and delayed the onset of G2 arrest. Hypoxia led to an earlier enhancement in cytokines secretion rate after X-irradiation compared to normoxic controls. Gene expression changes were most pronounced after the combined exposure to hypoxia and X-rays and pertained to senescence and different cell death pathways. In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.
Plant ways in Middle Bronze Age Anatolia—an archaeological interpretation of phytoliths and other plant remains from Zincirli Höyük, Türkiye
2024-11-23

Abstract This paper presents the results of phytolith analysis from Middle Bronze Age II (1800–1600 bce ) Zincirli Höyük, Türkiye. The study area was destroyed by a single fire event resulting in the preservation and recovery of several food processing installations (archaeological features) and restorable vessels (broken pots) in situ. The archaeological contexts were only slightly disturbed by later sedimentary and human activities. In this paper, we focus on the interpretation of the phytolith assemblages from samples collected from various archaeological features and destruction debris, including potential Phragmites (reed) matting, pottery contents and various kinds of installations. Complementary evidence from diatoms, dung spherulites and macrobotanical remains from this study and a previous one are also evaluated to add to the contextual significance of the phytolith record.
Phenol (bio)isosteres in drug design and development
2024-11-24

Abstract Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rapid metabolism, and potential toxicity. This review explores the use of phenol bioisosteres–structurally similar compounds that can mimic the biological activity of phenols while potentially offering improved drug‐like properties. We provide an extensive analysis of various phenol bioisosteres, including benzimidazolones, benzoxazolones, indoles, quinolinones, and pyridones, highlighting their impact on the pharmacokinetic and pharmacodynamic profiles of drugs. Case studies illustrate the successful application of these bioisosteres in enhancing metabolic stability, receptor selectivity, and overall therapeutic efficacy. Additionally, the review addresses the challenges associated with phenol bioisosterism, such as maintaining potency and avoiding undesirable side effects. By offering a detailed examination of current strategies and potential future directions, this review serves as a valuable resource for medicinal chemists seeking to optimize phenolic scaffolds in drug development. The insights provided herein aim to facilitate the design of more effective and safer therapeutic agents through strategic bioisosteric modifications.
A Geoeconomic Fix? European Industrial Policy on Semiconductors Amidst Global Competition
2024-11-24

Abstract This article observes that state actors in the emerging geoeconomic order are increasingly intervening in value chains that are politically regarded as strategic, with the aim of anchoring production capacities in their own territory. Drawing on David Harvey's concept of the ‘spatial fix’ and modifying it for the geoeconomic constellation, the article describes this phenomenon as a ‘geoeconomic fix’. However, this geoeconomic fix can only be achieved in co‐operation with industrial actors that possess strategic capabilities and technological know‐how. In a case study of European semiconductor policy from 2012 to 2023, the contribution traces changes in European industrial policy. Using process tracing, the article analyses key documents and statements from European Union (EU) institutions and industry actors. The results demonstrate that the geoeconomization of European semiconductor policy is accompanied by an increasing political focus on the spatial reorganization of the semiconductor value chain. The European semiconductor industry is driving this geoeconomization.
RENEWED: A follow-up study of the opicinumab phase 2 RENEW study in participants with acute optic neuritis
2024-11-24

The numerically increased VEP latency recovery with opicinumab treatment in RENEWED was consistent with those observed in the parent study RENEW. However, the VEP latency and clinical data in RENEWED should be interpreted with caution, given the nature of the follow-up study, the small sample size and the limitation in study design.