julilili42/papers huggingface dataset:
A splice donor in E6 influences keratinocyte immortalization by beta-HPV49
2025-01-22

ABSTRACT Human papillomaviruses (HPV) from the genus beta have been implicated in the development of cutaneous squamous cell cancer in epidermodysplasia verruciformis and organ transplant patients. In contrast to alpha-high-risk HPV, which cause ano-genital and oropharyngeal cancers, beta-HPV replication is not well understood. The beta-HPV49 transcriptome was analyzed by RNA sequencing using stable keratinocyte cell lines maintaining high levels of extrachromosomally replicating E8- genomes, which can be established due to a lack of the viral E8^E2 repressor protein. This analysis indicated the presence of four transcription start sites, two polyadenylation signals, and splice donor (SD) and acceptor sites consistent with the conserved gene expression patterns of animal and human PV. Surprisingly, a novel SD in the E6 oncogene (SD217) was identified resembling the SD in E6 of carcinogenic alpha-HPV. Mutation of SD217 enhanced E6 protein expression but had no influence on the growth of keratinocytes transduced with retroviral HPV49 E6 and E7 expression vectors. Inactivation of SD217 in the context of the HPV49 wild-type genome did not enable immortalization and prevented immortalization in the context of the E8- genome. The analysis of SD217 mutant genomes revealed a strong down-regulation of SD217 usage, but only weak effects on other viral transcripts. This suggests that SD217 does not contribute to immortalization by modulating viral gene expression. Usage of SD217 is increased in immortalized E8- cell lines compared with transiently transfected cells, which may indicate that long-term extrachromosomal maintenance requires reduced E6 protein levels. IMPORTANCE High-risk (hr) human papillomaviruses (HPV) from the genus alpha cause ano-genital and oropharyngeal cancers, whereas beta-HPV have been implicated to cause skin cancer in epidermodysplasia verruciformis and organ transplant patients. In contrast to alpha hr-HPV, the replication cycle of beta-HPV is not very well understood. Transcriptional profiling of beta-HPV49 by RNA sequencing reveals transcription start sites and splice sites conserved among HPV. Surprisingly, a splice donor site in the E6 oncogene (SD217), previously only described for hr-HPV, was identified that controls E6 oncoprotein levels and is required for immortalization of keratinocytes by the HPV49 genome.
Electronic-decay-process spectra including nuclear degrees of freedom
2025-01-22

In the field of chemistry, where nuclear motion has traditionally been a focal point, we now explore the ultrarapid electronic motion spanning attoseconds to femtoseconds, demonstrating that it is equally integral and relevant to the discipline. The advent of ultrashort attosecond pulse technology has revolutionized our ability to directly observe electronic rearrangements in atoms and molecules, offering a time-resolved insight into these swift processes. Prominent examples include Auger-Meitner decay and interparticle Coulombic decay. However, the real challenge lies in interpreting these observations, where theoretical models are indispensable. Building upon the analytical framework introduced by Fasshauer and Madsen [], which analyzed the spectra of electrons emitted during electronic decay processes from a purely electronic perspective, we extend this theoretical base to include nuclear dynamics, utilizing the Born-Oppenheimer approximation to deepen our understanding of the intricate interaction between electronic and nuclear motion in these processes. We illustrate the impact of incorporating nuclear degrees of freedom in several theoretical cases characterized by different numbers of vibrational bound states in both the electronic resonance and the electronic final state. This approach not only clarifies complex spectral features and unusual peak shapes but also demonstrates a method for extracting the energy differences between multiple vibrational resonance states through their distinctive interference patterns.
An investigation of the drug release kinetics of 3D-Printed two compartment Theophylline and Prednisolone tablets
2025-01-22

Pharmaceutical 3D printing (3DP) not only offers the possibility of dose personalization but also the co-administration of multiple active pharmaceutical ingredients (APIs) in one combination tablet. In this study, Theophylline (TPH) and Prednisolone (PSL) were printed as bi-tablets, which are single tablets with two distinct separate compartments. New findings show that the combination therapy of TPH with systemic corticosteroids shows a highly synergistic effect in the treatment of pulmonary diseases. For TPH, a drug with a narrow therapeutic window (NTW), precise sustained release requirements are mandatory, while PSL requires immediate drug release and is individually administered in doses specifically tied to the treatment progression. The study aims to understand the extent to which the combination of two tablet compartments influences the individual drug dissolution kinetics of the respective single compartments. Utilizing a full factorial statistical experimental design, various practically relevant doses were produced, investigated for their drug release, analyzed using different mathematical model fits, and compared with respective mono-tablets. The results show that the sustained drug release of TPH is not significantly influenced by the addition of a second compartment in relationship to respective doses. Individualization of bi-tablet doses while maintaining similar release profiles is possible with the given design setup, as release curves still show high similarity. In all tablet designs, PSL release occurred sufficiently fast, with the release rate correlating to the surface area-to-volume ratio (SA/V) as the main determining parameter.
Individual associations of self-reported sleep duration, sleep quality, chronotype and social jet lag with infectious disease risk
2025-01-23

Sleep deficiency is associated with infectious disease risk. However, little is known about the individual roles of different aspects of sleep, including sleep duration, sleep quality, sleep timing (assessed by chronotype) and sleep regularity (in the form of social jet lag) in this context. Here, we examined associations of the probability of reporting a cold or other infections with self-reported sleep duration, sleep quality and chronotype in a sample of 642 adults, and with social jet lag in a subsample of 274 adults. We found that short (≤ 6 h) and long sleepers (≥ 9 h) were more likely to report a cold in the past 30 days than average sleepers (7–8 h). Also, individuals with a definite evening chronotype were more likely to report a cold in the past 30 days than those with an intermediate chronotype, even when controlling for sleep duration. Finally, social jet lag was dose-dependently associated with the risk of reporting a cold in the past 12 months, independently of sleep duration, sleep quality and chronotype. No associations were found with sleep quality or with infections other than colds. The findings show that different aspects of sleep are independently associated with incidence of reported colds. This article is part of the Theo Murphy meeting issue ‘Circadian rhythms in infection and immunity’.
Characterization of the putative yeast mitochondrial triacylglycerol lipase Tgl2
2025-01-23

Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are the main components of mitochondrial membranes. In the cell, neutral lipids like triacylglycerides (TAGs) are stored in lipid droplets, playing an important role in maintaining cellular health. Enzymes like lipases mobilize these TAGs according to cellular needs. Neutral lipids have not yet been reported to play an important role in mitochondria so the presence of a putative TAG lipase-Tgl2, in yeast mitochondria is surprising. Moreover, TGL2 and MCP2, a high-copy suppressor for ER mitochondria encounter structure deficient cells, display genetic interactions suggesting a potential link of both proteins to lipid metabolism. In this study, we characterize in detail Tgl2. We show that Tgl2 forms dimers through intermolecular disulfide bridges and a cysteine-dependent high molecular weight complex. Furthermore, we could identify the lipase motif and catalytic triad of Tgl2 through in silico comparison with other lipases. Mutating each of the three catalytically active residues resulted in variants that failed to rescue the growth phenotype of mcp2Δ tgl2Δ double deletion strain supporting the assumption that these residues are indeed essential for the protein's function. Additionally, we discovered that the catalytically active aspartate residue (D259) is important for protein stability. Steady state level analyses with unstable variants of Tgl2 led to the identification of Yme1 as the protease responsible for its quality control. Finally, we provide evidence that the overall increase in TAGs in cells lacking Mcp2 and Tgl2 originates from the mitochondria. Collectively, our study provides new insights into a key player in mitochondrial lipid homeostasis.
Standardized Reporting of HCC with LI-RADS and mRECIST: Update on the Situation in Germany
2025-01-23

Abstract Online survey about the current status of CT protocols in hepatocellular carcinoma (HCC) in the year 2023/2024. Moreover, the usage of structured reporting using LI-RADS and mRECIST was surveyed and the results were compared with a survey from 2020. Radiologists working in outpatient or inpatient care in Germany were invited. The survey was conducted between 10/2022 and 06/2023 and between 06/2024 and 08/2024. HCC-related questions were asked regarding the commonly used imaging modalities, body coverage, and contrast phases in CT, as well as the usage of structured assessment and treatment response using mRECIST and LI-RADS. More than half of the participants stated that they “frequently” perform imaging of HCC. In the CT protocol, acquisition of a pre-contrast phase was widespread. While a late arterial and a portal venous contrast phase was acquired in most cases, a delayed phase was used much less frequently (at small and medium-sized hospitals only in 26.5%). For staging, LI-RADS was used in structured reports in only 13%; for response monitoring mRECIST was used at university hospitals in only 26.5% and LI-RADS in 14.7%, whereas these have been almost never used in routine practice at all other sites. The main reasons given for the lack of application were the expenditure of time, the lack of reporting templates, problems with integration into the IT infrastructure and a lack of reimbursement. The recommendation of a three phase CT examination in late arterial, portal venous, and delayed phase for HCC diagnostics according to LI-RADS is only partially implemented in Germany. Structured reporting for staging and response monitoring using LI-RADS and mRECIST was at a similarly low level in Germany in 2023 compared to 2020. Possible solutions include the development and distribution of online educational resources, structured reporting templates, and inexpensive IT solutions.
Long-term human influence on the demography and genetic diversity of the hyperdominant Bertholletia excelsa in the Amazon Basin
2025-01-24

The Amazon rainforest is characterized by a limited number of hyperdominant trees that play an oversized role in its ecosystems, nutrient cycle, and rainfall production. Some of these, such as the Brazil nut, appear to have been intensively exploited and dispersed by Indigenous populations since their earliest arrival in this part of South America around 13,000 years ago. However, the genetic diversity-and geographic structure-of these species remains poorly understood, as does their exact relationship with past human land use. We use a new genome assembly for Brazil nut to analyze 270 individuals sampled at areas with varying intensities of archaeological evidence. We demonstrate that overall low genetic diversity, with a notable decrease since the Late Pleistocene, is accompanied by significant geographic structure, where evidence for improved gene flow and regeneration by long-term traditional human management is linked to increased genetic diversity. We argue that historical perspectives on the genetic diversity of key tree species, such as the Brazil nut, can support the development of more active management strategies today.
Universality of the close packing properties and markers of isotropic-to-tetratic crossover in quasi-one-dimensional superdisk fluid
2025-01-24

We study equilibrium states and ordering regimes of a quasi-one-dimensional system of hard superdisks (anisotropic particles interpolating between disks and squares) where the centers of the particles are constrained to move on a line. A continuous change from a quasi-isotropic to a tetratic regime is found upon increasing the density. Somewhat unexpected, for isobaric states, systems with larger and more anisotropic particles in the tetratic regime are denser than systems with smaller and less anisotropic particles in a quasi-isotropic regime. Close packing behaviour is characterised by exponents describing the behaviour of the pressure, the angular fluctuations and the angular correlation length. We obtain two universal, shape-independent relations between them.
Genetically attenuated parasites show promise as a next-generation malaria vaccine
2025-01-24

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al. demonstrated in recent Phase 1/2a trials that GA2 parasites, designed to arrest late during liver-stage development and transmitted via mosquito bites, can induce substantial protection against sporozoite challenge infection.
Immersive exposure to simulated visual hallucinations modulates high-level human cognition
2025-01-24

Psychedelic drugs offer valuable insights into consciousness, but disentangling their causal effects on perceptual and high-level cognition is nontrivial. Technological advances in virtual reality (VR) and machine learning have enabled the immersive simulation of visual hallucinations. However, comprehensive experimental data on how these simulated hallucinations affects high-level human cognition is lacking. Here, we exposed human participants to VR panoramic videos and their psychedelic counterparts generated by the DeepDream algorithm. Participants exhibited reduced task-switching costs after simulated psychedelic exposure compared to naturalistic exposure, consistent with increased cognitive flexibility. No significant differences were observed between naturalistic and simulated psychedelic exposure in linguistic automatic association tasks at word and sentence levels. Crucially, visually grounded high-level cognitive processes were modulated by exposure to simulated hallucinations. Our results provide insights into the interdependence of bottom-up and top-down cognitive processes and altered states of consciousness without pharmacological intervention, potentially informing both basic neuroscience and clinical applications.
Dynamic Accommodation Responses in Subjects Wearing Myopia Control Spectacles Modifying Peripheral Refraction
2025-01-24

No effect on accommodation responses was found in subjects wearing different types of myopia control lenses. This finding indicates that the induced changes in the ocular peripheral optics do not have an impact on accommodation.
Spatial Dynamics and Drivers of Urban Growth in Thua Thien Hue Province, Vietnam: Insights for Urban Sustainability in the Global South
2025-01-25

Investigating the historical patterns of urban growth and their drivers is crucial to informing sustainable urban planning policies, especially in cities of the Global South. In Vietnam, most studies focus primarily on city extents, offering little insight into urban growth across various provinces. This study, therefore, combined categorical land use and land cover change detection, Random Forest classification and expert interviews to quantify the urban growth between 2000 and 2020, assess urban encroachment upon other land uses, and identify key drivers shaping this growth in Thua Thien Hue province. Findings show that the urban land areas were 27.94 km2, 82.97 km2, and 209.80 km2 in 2000, 2010, and 2020, respectively. Urban encroachment upon other land use types, especially cropland, barren land, rice paddies, shrubs, and forests, was observed in these periods. Additionally, accessibility to built-up areas, DEM, proximity to rice paddies, slope, proximity to street roads, accessibility to social areas, and proximity to cropland are the major spatial drivers of urban growth in the province. The study concludes that rapid urban expansion is evident in the province at the expense of other land use types, especially agricultural land use types, which may impact food security and livelihoods in the province.
Automatic Generation of Fast and Accurate Performance Models for Deep Neural Network Accelerators
2025-01-25

Implementing Deep Neural Networks (DNNs) on resource-constrained edge devices is a challenging task that requires tailored hardware accelerator architectures and a clear understanding of their performance characteristics when executing the intended AI workload. To facilitate this, we present an automated generation approach for fast performance models to accurately estimate the latency of a DNN mapped onto systematically modeled and concisely described accelerator architectures. Using our accelerator architecture description method, we modeled representative DNN accelerators such as Gemmini, UltraTrail, Plasticine-derived, and a parameterizable systolic array. Together with DNN mappings for those modeled architectures, we perform a combined DNN/hardware dependency graph analysis, which enables us, in the best case, to evaluate only 154 loop kernel iterations to estimate the performance for 4.19 billion instructions achieving a significant speedup. We outperform regression and analytical models in terms of mean absolute percentage error (MAPE) compared with simulation results, while being several magnitudes faster than an RTL simulation.
Influence of two different printing methods on the accuracy of full-guided implant insertion – a laboratory study in undergraduate dental students
2025-01-26

Abstract Objectives The aim of the present study was to compare the accuracy of fully guided implant insertion in vitro achieved by two fabrication methods in a cohort of undergraduates. We hypothesized that both methods achieve a comparable accuracy. Methods Surface scans and cone beam computed tomography images of 48 mandibular models were matched. For each model, two surgical guides enabling a fully guided implant insertion in the region of the first molar on the left or the right side were virtually designed. Fabrication by either Digital Light Processing (DLP) or Fused Filament Fabrication (FFF) followed. Subsequently, 96 implants using the guides were inserted into the models by 48 undergraduate students. The accuracy of the implant insertion was assessed radiographically, followed by statistical analysis. Additionally, all participants completed a questionnaire. Results The implants inserted using guides made by DLP showed a higher accuracy compared to guides made by FFF. The mean three-dimensional deviation was 1.94 ± 1.05 vs. 3.35 ± 2.03 degrees ( p &lt; 0.001). The evaluation of the questionnaires revealed mainly theoretical knowledge and a pronounced interest in implant dentistry. Discussion The main hypothesis has to be rejected as there were statistically significant differences in accuracy. However, it is possible to teach students the principles of guided implant dentistry and the digital workflow. Furthermore, the initial and running costs for the FFF workflow are substantially lower enabling a higher practicability for undergraduate education. Conclusion Despite the lower accuracy of the templates made from FFF the method seems to be suitable for laboratory hands-on courses for undergraduates.
The receptor-like kinases BIR1 and BIR3 modulate antiviral resistance by different mechanisms
2025-01-26

Abstract The BAK1-INTERACTING RECEPTOR-LIKE KINASE (BIR) proteins, including BIR1, are negative regulators of cell death and defense in Arabidopsis. Although BIR1 is upregulated during viral infections, its role in virus defense remains unclear. Here, we demonstrate a conserved role for the BIR family as modulators of antiviral resistance in Arabidopsis. During tobacco rattle virus (TRV) infection, BIR gene expression is regulated by antagonistic interactions between salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Genetic evidence shows that BIR1, BIR2, and BIR3 negatively regulate TRV resistance via distinct mechanisms. The antiviral phenotype in bir1-1 mutants is unaffected by mutations in the receptor-like kinases (RLK) BAK1, SOBIR1, or in the lipase-like PAD4. While BIR1 induction partially suppresses PTI marker gene expression, it does not affect early PTI responses such as reactive oxygen species (ROS) production or ethylene accumulation. BIR1 also inhibits plasmodesmata (PD) callose deposition and facilitates virus spread. Our data suggest that BIR1 modulates antiviral defense through mechanisms that include PTI gene expression, PD callose deposition alongside yet unidentified pathways independent of ROS or BAK1, SOBIR1, or PAD4 signaling components. In contrast, BIR3 suppresses an antiviral resistance pathway against TRV that requires BAK1 and the lipases PAD4 and EDS1. Our results suggest that BIR3 controls an NLR-dependent ETI-like response that restricts virus proliferation without triggering a hypersensitive response. These findings highlight the distinct roles of BIR family members in regulating antiviral defense in Arabidopsis.
Magnetic vector field mapping of the stimulated abductor digiti minimi muscle with optically pumped magnetometers
2025-01-27

Abstract Objective. Mapping the myomagnetic field of a straight and easily accessible muscle after electrical stimulation using triaxial optically pumped magnetometers (OPMs) to assess potential benefits for magnetomyography (MMG). Approach. Six triaxial OPMs were arranged in two rows with three sensors each along the abductor digiti minimi (ADM) muscle. The upper row of sensors was inclined by 45° with respect to the lower row and all sensors were aligned closely to the skin surface without direct contact. Then, the electromagnetic muscle activity was electrically evoked utilizing stepwise increasing currents at the cubital tunnel at the ulnar nerve. Evoked myomagnetic activity was recorded with 18 channels, three per sensor. As the measurements were performed in PTB’s magnetically shielded room (BMSR-2) no averaging and only moderate filtering was applied. Main results. The myomagnetic vector field could be successfully mapped. The obtained spatial structure with a radial symmetry corresponds to the expectations from the ADM’s parallel muscle architecture. The temporal evolution exhibits an up to four-phasic shape. Implications for future experiments are derived and needs for sensor performance improvements are identified . Significance. The use of an OPM array with small (∼3 mm edge length) sensing voxels enabled the mapping of the magnetic vector field of the ADM. This allowed visualization of the spatiotemporal evolution of the muscle’s evoked magnetic field and gives implications for future experiments. In the future, high density OPM grids may enable high-accuracy determination of muscle parameters such as innervation zone position, pennation angle, and propagation velocities.