julilili42/papers huggingface dataset:
Transposon dynamics in the emerging oilseed cropThlaspi arvense
2023-05-24

Abstract Genome evolution is partly driven by the mobility of transposable elements (TEs) which often leads to deleterious effects, but their activity can also facilitate genetic novelty and catalyze local adaptation. We explored how the intraspecific diversity of TE polymorphisms is shaping the broad geographic success and adaptation capacity of the emerging oil crop Thlaspi arvense . We achieved this by classifying the TE inventory of this species based on a high-quality genome assembly, age estimation of retrotransposon TE families and a comprehensive assessment of their mobilization potential. Our survey of TE insertion polymorphisms (TIPs) captured 280 accessions from 12 regions across the Northern hemisphere. We quantified over 90,000 TIPs, with their distribution mirroring genetic differentiation as measured by single nucleotide polymorphisms (SNPs). The number and types of mobile TE families vary substantially across populations, but there are also shared patterns common to all accessions. We found that Ty3/Athila elements are the main drivers of TE diversity in T. arvense populations, while a single Ty1/Alesia lineage might be particularly important for molding transcriptome divergence. We further observed that the number of retrotransposon TIPs is associated with variation at genes related to epigenetic regulation while DNA transposons are associated with variation at a Heat Shock Protein (HSP19). We propose that the high rate of mobilization activity can be harnessed for targeted gene expression diversification, which may ultimately present a toolbox for the potential use of transposition in breeding and domestication of T. arvense .
ZING: An Eye-Tracking Experiment Software for Organization and Presentation of Omnidirectional Stimuli in Virtual Reality
2023-05-24

The growing field of eye-tracking enables many researchers to investigate human (subconscious) behavior unobtrusively, naturally, and non-invasive. For that, a highly natural, immersive, and controllable environment is essential to investigators. Currently, next to mobile eye-tracking in the wild, virtual reality is becoming state-of-the-art for such experiments, combining several eye-tracking modalities' strengths. Next to simulations, omnidirectional video footage is massively used. 360°cameras capture these videos with resolutions of up to 16k. Afterward, they can be replayed on virtual reality glasses to learn about human behavior in a realistic, highly controlled environment. However, the pipeline from stitched video to eye-tracking experiment results depends on costly proprietary or self-developed software that lacks standardization, leading to recurrent reimplementation. This paper describes an open-source stimuli organization and presentation software implementation that enables researchers to easily organize their stimuli in a standardized way and conduct eye-tracking studies in virtual reality with a few clicks without knowledge about coding or technical details. The code is available at https://bitbucket.org/benediktwhosp/zing
Pupil Diameter during Counting Tasks as Potential Baseline for Virtual Reality Experiments
2023-05-24

Pupil diameter is a reliable indicator of mental effort, but it must be baseline corrected to account for its idiosyncratic nature. Established methods for measuring baselines cannot be applied in virtual reality (VR) experiments. To reliably measure a pupil diameter baseline in VR, we propose a short testing environment of visual arithmetic tasks. In an experiment with 66 university students, we analyzed external reliability and internal validity criteria for pupil diameter measures during counting and summation tasks. During the counting task, we found a high retest reliability between stimulus intervals. Acceptable retest reliability was found for task repetition at a second measuring time. Analyzing internal validity, we found that pupil diameter increased with task difficulty comparing both tasks. Further, a linear effect was found between the pupil diameter amplitude and luminance levels. Our findings highlight the potential of counting tasks as a pupil diameter baseline for VR experiments.
Investigating Cognitive Load for Tasks with Mathematics and Chemistry Context through Eye Tracking
2023-05-24

Changes in mathematical representation are an essential part of many STEM fields, especially chemistry. In order to better understand these transitions between different representations, we investigated possible eye-tracking indicators of cognitive load during a task that had two experimental conditions: one was purely mathematical, the other one was similar, but had a chemical context. We used pupil diameter, fixation duration, and pupil fluctuations as measured through the IPA as indicators of cognitive load. Our preliminary results indicate that there may not be a significant difference in cognitive load between the two conditions, which in turn suggests that a chemical context does not impose additional cognitive load on participants. The present study may serve as a starting point to investigate this issue further and shed light on the potential influence of a chemical context on cognitive load.
Body exposure and vocal analysis: validation of fundamental frequency as a correlate of emotional arousal and valence
2023-05-24

Introduction Vocal analysis of fundamental frequency ( f 0) represents a suitable index to assess emotional activation. However, although f 0 has often been used as an indicator of emotional arousal and different affective states, its psychometric properties are unclear. Specifically, there is uncertainty regarding the validity of the indices of f 0 mean and f 0 variabilitymeasures ( f 0 dispersion , f 0 range , and f 0 SD ) and whether higher or lower f 0 indices are associated with higher arousal in stressful situations. The present study therefore aimed to validate f 0 as a marker of vocally encoded emotional arousal, valence, and body-related distress during body exposure as a psychological stressor. Methods N = 73 female participants first underwent a 3-min, non-activating neutral reference condition, followed by a 7-min activating body exposure condition. Participants completed questionnaires on affect (i.e., arousal, valence, body-related distress), and their voice data and heart rate (HR) were recorded continuously. Vocal analyses were performed using Praat, a program for extracting paralinguistic measures from spoken audio. Results The results revealed no effects for f 0 and state body dissatisfaction or general affect. F 0 mean correlated positively with self-reported arousal and negatively with valence, but was not correlated with HR mean/maximum . No correlations with any measure were found for any f 0 variabililtymeasures . Discussion Given the promising findings regarding f 0 mean for arousal and valence and the inconclusive findings regarding f 0 as a marker of general affect and body-related distress, it may be assumed that f 0 mean represents a valid global marker of emotional arousal and valence rather than of concrete body-related distress. In view of the present findings regarding the validity of f 0, it may be suggested that f 0 mean , but not f 0 variabilitymeasures , can be used to assess emotional arousal and valence in addition to self-report measures, which is less intrusive than conventional psychophysiological measures.
Photolytic Decarbonylation of Oxalyl Diisothiocyanate in Solid Argon Matrices tosyn‐antiCarbonyl Diisothiocyanate and Its Isomerization
2023-05-24

Abstract Oxalyl diisothiocyanate, ((CO)NCS) 2 , has been studied in solid argon matrices at 4.2 K with the aid of infrared (IR) spectroscopy. The spectra show mainly signals attributed to the most stable anti‐anti conformer, which is corroborated by comparison to computed anharmonic fundamental IR transitions. Upon irradiation with 254 nm UV light, oxalyl diisothiocyanate eliminates carbon monoxide under formation of carbonyl diisothiocyanate, CO(NCS) 2 . This reaction is only slightly exothermic by 0.4 kcal mol −1 at the DLPNO‐CCSD(T)/def2‐QZVPP//B3LYP‐D3/def2‐TZVPP level of theory. Remarkably, photolysis produces mostly the less stable syn‐anti conformer of carbonyl diisothiocyanate. Subsequent annealing at 30 K for two minutes results in a structural relaxation to the 0.7 kcal mol −1 more stable syn‐syn conformer confirming a low torsional barrier height between the isomers.
The influence of pupil ellipse noise on the convergence time of a glint-free 3D eye tracking algorithm
2023-05-24

Eye-tracking is a key sensing technology for upcoming retinal projection augmented reality (AR) glasses. State-of-the-art eye-tracking sensor technologies rely on video oculography (VOG) and 3D model based gaze estimation algorithms, which infer gaze from observations of the projected pupil over time. The convergence time of these algorithms relies heavily on the pupil ellipse fitting accuracy. In this work, we investigate the effects of pupil ellipse contour noise and pupil center noise on the convergence time of a state-of-the-art eye-tracking approach and show that the convergence time relies heavily on a sub-pixel accurate pupil ellipse fitting and can reach tens of seconds for inaccurately fitted ellipses.
Self-regulation of the posterior-frontal brain activity with real-time fMRI neurofeedback to influence conscious perception
2023-05-24

Abstract The Global Neuronal Workspace (GNW) hypothesis states that the visual percept is available to conscious awareness only if recurrent long-distance interactions among distributed brain regions activate neural circuitry extending from posterior regions to prefrontal regions above a certain excitation threshold. To directly test this hypothesis, we trained human participants to increase blood oxygenation level-dependent (BOLD) signals with real-time functional magnetic resonance imaging (rtfMRI) based neurofeedback simultaneously in four specific regions of the occipital, temporal, insular and prefrontal parts of the brain. Specifically, we hypothesized that up-regulation of the mean BOLD activity in the posterior-frontal brain regions lowers the perceptual threshold for visual stimuli, while down-regulation raises the threshold. Our results showed that participants were able to perform up-regulation of the posterior-frontal brain activity but not down-regulation. Furthermore, the up-regulation training led to a significant reduction of the visual perceptual threshold, but no significant change of perceptual threshold was observed after down-regulation training. These findings partially support the GNW hypothesis of consciousness perception, to the extent that up-regulation of the posterior-frontal regions improves conscious awareness of stimuli. However, further questions as to whether the posterior-frontal regions can be down-regulated at all, and whether down-regulation raises the perceptual threshold remain unanswered.
Reaction-Limited Quantum Reaction-Diffusion Dynamics
2023-05-25

We consider the quantum nonequilibrium dynamics of systems where fermionic particles coherently hop on a one-dimensional lattice and are subject to dissipative processes analogous to those of classical reaction-diffusion models. Particles can either annihilate in pairs, A+A→0, or coagulate upon contact, A+A→A, and possibly also branch, A→A+A. In classical settings, the interplay between these processes and particle diffusion leads to critical dynamics as well as to absorbing-state phase transitions. Here, we analyze the impact of coherent hopping and of quantum superposition, focusing on the so-called reaction-limited regime. Here, spatial density fluctuations are quickly smoothed out due to fast hopping, which for classical systems is described by a mean-field approach. By exploiting the time-dependent generalized Gibbs ensemble method, we demonstrate that quantum coherence and destructive interference play a crucial role in these systems and are responsible for the emergence of locally protected dark states and collective behavior beyond mean field. This can manifest both at stationarity and during the relaxation dynamics. Our analytical results highlight fundamental differences between classical nonequilibrium dynamics and their quantum counterpart and show that quantum effects indeed change collective universal behavior.
Brain‐oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double‐blind three‐ arm parallel‐group exploratory trial comparing personalized, non‐ personalized and sham repetitive transcranial magnetic stimulation (Acronym: BOSS-STROKE)
2023-05-25

Abstract Background Stroke is a major cause of death and the most frequent cause of permanent disability in western countries. Repetitive transcranial brain stimulation (rTMS) has been used to enhance neuronal plasticity after stroke, yet with only moderate effect sizes. Here we will apply a highly innovative technology that synchronizes rTMS to specific brain states identified by real-time analysis of electroencephalography. Methods One hundred forty-four patients with early subacute ischemic motor stroke will be included in a multicenter 3-arm parallel, randomized, double-blind, standard rTMS and sham rTMS-controlled exploratory trial in Germany. In the experimental condition, rTMS will be synchronized to the trough of the sensorimotor μ-oscillation, a high-excitability state, over ipsilesional motor cortex. In the standard rTMS control condition the identical protocol will be applied, but non-synchronized to the ongoing μ-oscillation. In the sham condition, the same μ-oscillation-synchronized protocol as in experimental condition will be applied, but with ineffective rTMS, using the sham side of an active/placebo TMS coil. The treatment will be performed over five consecutive work days (1,200 pulses per day, 6,000 pulses total). The primary endpoint will be motor performance after the last treatment session as measured by the Fugl-Meyer Assessment Upper Extremity. Discussion This study investigates, for the first time, the therapeutic efficacy of personalized, brain-state-dependent rTMS. We hypothesize that synchronization of rTMS with a high-excitability state will lead to significantly stronger improvement of paretic upper extremity motor function than standard or sham rTMS. Positive results may catalyze a paradigm-shift towards personalized brain-state-dependent stimulation therapies. Trial registration This study was registered at ClinicalTrials.gov (NCT05600374) on 10–21-2022.
Ablation of C-type natriuretic peptide/cGMP signaling in fibroblasts exacerbates adverse cardiac remodeling in mice
2023-05-25

Excessive activation of cardiac fibroblasts (CFs) in response to injury provokes cardiac fibrosis, stiffness, and failure. The local mediators counterregulating this response remain unclear. Exogenous C-type natriuretic peptide (CNP) exerts antifibrotic effects in preclinical models. To unravel the role of the endogenous hormone, we generated mice with fibroblast-restricted deletion (KO) of guanylyl cyclase-B (GC-B), the cGMP-synthesizing CNP receptor. CNP activated GC-B/cGMP signaling in human and murine CFs, preventing proliferative and promigratory effects of angiotensin II (Ang II) and TGF-β. Fibroblast-specific GC-B-KO mice showed enhanced fibrosis in response to Ang II infusions. Moreover, after 2 weeks of mild pressure overload induced by transverse aortic constriction (TAC), such KO mice had augmented cardiac fibrosis and hypertrophy, together with systolic and diastolic contractile dysfunction. This was associated with increased expression of the profibrotic genes encoding collagen I, III, and periostin. Notably, such responses to Ang II and TAC were greater in female as compared with male KO mice. Enhanced Ang II-induced CNP expression in female hearts and augmented GC-B expression and activity in female CFs may contribute to this sex disparity. The results show that paracrine CNP signaling in CFs has antifibrotic and antihypertrophic effects. The CNP/GC-B/cGMP pathway might be a target for therapies combating pathological cardiac remodeling.
Design and Optimization of Novel Benzimidazole- and Imidazo[4,5-b]pyridine-Based ATM Kinase Inhibitors with Subnanomolar Activities
2023-05-25

The ATM kinase is a promising target in cancer treatment as an important regulator of the cellular response to DNA double-strand breaks. In this work, we present a new class of specific benzimidazole-based ATM inhibitors with picomolar potency against the isolated enzyme and favorable selectivity within relative PIKK and PI3K kinases. We could identify two promising inhibitor subgroups with significantly different physicochemical properties, which we developed simultaneously. These efforts lead to numerous highly active inhibitors with picomolar enzymatic activities. Furthermore, initial low cellular activities on A549 cells could be increased significantly in numerous examples resulting in cellular IC<sub>50</sub> values in the subnanomolar range. Further characterization of the highly potent inhibitors <b>90</b> und <b>93</b> revealed promising pharmacokinetic properties and strong activities in organoids in combination with etoposide. Additionally, <b>93</b> showed no off-target activities within a kinome-representative mini kinase panel, with favorable selectivities within the PIKK- and PI3K-families.
Noninferiority of Local Control and Comparable Toxicity of Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Breast Cancer: 5-Year Results of the IMRT-MC2 Phase III Trial
2023-05-25

The 5-year results of the IMRT-MC2 trial provide strong evidence that the application of conventionally fractionated simultaneous integrated boost irradiation for patients with breast cancer is both safe and effective, with noninferior local control compared with 3-dimensional conformal radiation therapy with sequential boost.
Sibling oocytes cultured in a time-lapse versus benchtop incubator: how time-lapse incubators improve blastocyst development and euploid rate
2023-05-25

Summary The aim was to study whether a limited exposure of embryos outside the incubator has an effect on embryo development, blastocyst quality and euploid outcomes. This retrospective study was performed at ART Fertility Clinics, Abu Dhabi, United Arab Emirates (UAE) between March 2018 and April 2020 and included 796 mature sibling oocytes that were split randomly between two incubators after intracytoplasmic sperm injection (ICSI): an EmbryoScopeTM (ES) incubator and a benchtop incubator, G185 K-SYSTEMS (KS). The fertilization, cleavage, embryo/blastocyst qualities, useable blastocyst and euploid rates were assessed to evaluate the incubator performance. In total, 503 (63.2%) mature oocytes were cultured in the EmbryoScope and 293 (36.8%) in the K-SYSTEMS. No differences were observed in fertilization rate (79.3% vs 78.8%, P = 0.932), cleavage rate (98.5% vs 99.1%, P = 0.676) and embryo quality on Day 3 ( P = 0.543) between both incubators, respectively. Embryos cultured in the EmbryoScope, had a significantly higher chance of being biopsied (64.8% vs 49.6%, P &lt; 0.001). Moreover, a significantly higher blastocyst biopsy rate was observed on Day 5 in the EmbryoScope (67.8% vs 57.0%, P = 0.037), with a highly significant increased euploid rate (63.5% vs 37.4%, P = 0.001) and improved blastocyst quality ( P = 0.008). We found that exposure of embryos outside the incubator may negatively affect the in vitro blastocyst development and euploid rate on Day 5.
Indolyl-chalcone derivatives trigger apoptosis in cisplatin-resistant mesothelioma cells through aberrant tubulin polymerization and deregulation of microtubule-associated proteins
2023-05-25

Introduction Malignant pleural mesothelioma (MPM) is a neoplasm with dismal prognosis and notorious resistance to the standard therapeutics cisplatin and pemetrexed. Chalcone derivatives are efficacious anti-cancer agents with minimal toxicity and have, therefore, gained pharmaceutical interest. Here, we investigated the efficacy of CIT-026 and CIT-223, two indolyl-chalcones (CITs), to inhibit growth and viability of MPM cells and defined the mechanism by which the compounds induce cell death. Methods The effects of CIT-026 and CIT-223 were analyzed in five MPM cell lines, using viability, immunofluorescence, real-time cell death monitoring, and tubulin polymerization assays, along with siRNA knockdown. Phospho-kinase arrays and immunoblotting were used to identify signaling molecules that contribute to cell death. Results CIT-026 and CIT-223 were toxic in all cell lines at sub-micromolar concentrations, in particular in MPM cells resistant to cisplatin and pemetrexed, while normal fibroblasts were only modestly affected. Both CITs targeted tubulin polymerization via (1) direct interaction with tubulin and (2) phosphorylation of microtubule regulators STMN1, CRMP2 and WNK1. Formation of aberrant tubulin fibers caused abnormal spindle morphology, mitotic arrest and apoptosis. CIT activity was not reduced in CRMP2-negative and STMN1-silenced MPM cells, indicating that direct tubulin targeting is sufficient for toxic effects of CITs. Discussion CIT-026 and CIT-223 are highly effective inducers of tumor cell apoptosis by disrupting microtubule assembly, with only modest effects on non-malignant cells. CITs are potent anti-tumor agents against MPM cells, in particular cells resistant to standard therapeutics, and thus warrant further evaluation as potential small-molecule therapeutics in MPM.
The hemodynamic initial-dip consists of both volumetric and oxymetric changes reflecting localized spiking activity
2023-05-25

The initial-dip is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed, and its precise neuronal correlates are unknown. Here we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in deoxy-Hb (HbR), with an early decrease and later rebound. Both the HbT-dip and HbR-rebound were strongly correlated to highly localized spiking activity. However, HbT decreases were always large enough to counter the spiking-induced increase in HbR. We find that the HbT-dip counters spiking induced HbR increases, imposing an upper-limit to HbR concentration in the capillaries. Building on our results, we explore the possibility of active venule dilation (purging) as a possible mechanism for the HbT dip.