julilili42/papers huggingface dataset:
Quasibound States, Stability and Wave Functions of the Test Fields in the Consistent 4D Einstein–Gauss–Bonnet Gravity
2023-04-25

We examine the interaction between quantum test particles and the gravitational field generated by a black hole solution that was recently obtained in the consistent 4-dimensional Einstein–Gauss–Bonnet gravity. While quasinormal modes of scalar, electromagnetic, and Dirac fields have been recently studied in this theory, there is no such study for the quasibound states. Here, we calculate the spectrum of quasibound states for the test fields in a spherically symmetric and asymptotically flat black hole solution in the consistent 4-dimensional Einstein–Gauss–Bonnet gravity. The quasispectrum of resonant frequencies is obtained by using the polynomial condition associated to the general Heun functions. We also discuss the stability of the systems for some values of the Gauss-Bonnet coupling constant.
Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction
2023-04-25

Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remains largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD. Therefore, we conducted a transcriptome study of SAD and ELA performing RNA sequencing in peripheral blood samples. Analyzing differential gene expression between individuals suffering from SAD with high or low levels of ELA and healthy individuals with high or low levels of ELA, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD while no significant differences in expression were identified with respect to ELA. The most significantly expressed gene was MAPK3 ( p = 0.003) being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analysis ( WGCNA ) identified only modules significantly associated with ELA ( p ≤ 0.05), not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3 revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD. In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.
Next-generation phenotyping integrated in a national framework for patients with ultra-rare disorders improves genetic diagnostics and yields new molecular findings
2023-04-25

Abstract Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency. ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders. To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization. The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.
Evolution of Lipochitooligosaccharide Binding to a LysM-RLK for Nodulation in Medicago truncatula
2023-04-25

Abstract Lysin motif receptor–like kinases (LysM-RLKs) are involved in the perception of chitooligosaccharides (COs) and related lipochitooligosaccharides (LCOs) in plants. Expansion and divergence of the gene family during evolution have led to various roles in symbiosis and defense. By studying proteins of the LYR-IA subclass of LysM-RLKs of the Poaceae, we show here that they are high-affinity LCO-binding proteins with a lower affinity for COs, consistent with a role in LCO perception to establish arbuscular mycorrhiza (AM). In Papilionoid legumes, whole-genome duplication has resulted in two LYR-IA paralogs, MtLYR1 and MtNFP in Medicago truncatula, with MtNFP playing an essential role in root nodule symbiosis with nitrogen-fixing rhizobia. We show that MtLYR1 has retained the ancestral LCO-binding characteristic and is dispensable for AM. Domain swapping between the three LysMs of MtNFP and MtLYR1 and mutagenesis in MtLYR1 suggest that the MtLYR1 LCO-binding site is on the second LysM and that divergence in MtNFP led to better nodulation, but surprisingly with decreased LCO binding. These results suggest that divergence of the LCO-binding site has been important for the evolution of a role of MtNFP in nodulation with rhizobia.
Stage-dependent biomarker changes in spinocerebellar ataxia type 3
2023-04-25

Abstract Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI. Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia. The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3.
Synthesis of Rhodomyrtone Analogs Modified at C7
2023-04-25

Abstract We developed a route to rhodomyrtone analogs that feature different acyl groups at C7. Since electrophilic substitution reactions on the aryl part of the rhodomyrtone core led to C5 derivatives, the C5 position was blocked by a chlorine. Subsequent Duff type formylation followed by Grignard addition to the aldehyde group and oxidation gave various phenones. The benzyl protecting groups were removed by hydrogenation or boron tribromide. Some derivatives turned out to be quite active against multiple resistant Staphylococcus aureus strains and a rhodomyrtone resistant mutant (Rom R ). The chlorine at C5 seems to have a beneficial effect on the antibacterial activity.
Heading toward Miniature Sensors: Electrical Conductance of Linearly Assembled Gold Nanorods
2023-04-25

Metal nanoparticles are increasingly used as key elements in the fabrication and processing of advanced electronic systems and devices. For future device integration, their charge transport properties are essential. This has been exploited, e.g., in the development of gold-nanoparticle-based conductive inks and chemiresistive sensors. Colloidal wires and metal nanoparticle lines can also be used as interconnection structures to build directional electrical circuits, e.g., for signal transduction. Our scalable bottom-up, template-assisted self-assembly creates gold-nanorod (AuNR) lines that feature comparably small widths, as well as good conductivity. However, the bottom-up approach poses the question about the consistency of charge transport properties between individual lines, as this approach leads to heterogeneities among those lines with regard to AuNR orientation, as well as line defects. Therefore, we test the conductance of the AuNR lines and identify requirements for a reliable performance. We reveal that multiple parallel AuNR lines (&gt;11) are necessary to achieve predictable conductivity properties, defining the level of miniaturization possible in such a setup. With this system, even an active area of only 16 μm2 shows a higher conductance (~10−5 S) than a monolayer of gold nanospheres with dithiolated-conjugated ligands and additionally features the advantage of anisotropic conductance.
A 6-items Questionnaire (6-QMD) captures a Mediterranean like dietary pattern and is associated with memory performance and hippocampal volume in elderly and persons at risk for Alzheimer’s disease
2023-04-25

BACKGROUND: There is evidence that adherence to Mediterranean-like diet reduces cognitive decline and brain atrophy in Alzheimer's disease (AD). However, lengthy dietary assessments, such as food frequency questionnaires (FFQs), discourage more frequent use. OBJECTIVE: Here we aimed to validate a 6-items short questionnaire for a Mediterranean-like diet (6-QMD) and explore its associations with memory performance and hippocampal atrophy in healthy elders and individuals at risk for AD. METHODS: We analyzed 938 participants (N = 234 healthy controls and N = 704 participants with an increased AD risk) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). The 6-QMD was validated against the Mediterranean Diet (MeDi) score and the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) score, both derived from a detailed FFQ. Furthermore, associations between the 6-QMD and memory function as well as hippocampal atrophy were evaluated using linear regressions. RESULTS: The 6-QMD was moderately associated with the FFQ-derived MeDi adherence score (ρ = 0.25, p &lt; 0.001) and the MIND score (ρ = 0.37, p= &lt; 0.001). Higher fish and olive oil consumption and lower meat and sausage consumption showed significant associations in a linear regression, adjusted for diagnosis, age, sex and education, with memory function (β = 0.1, p = 0.008) and bilateral hippocampal volumes (left: β = 0.15, p &lt; 0.001); (right: β = 0.18, p &lt; 0.001)). CONCLUSIONS: The 6-QMD is a useful and valid brief tool to assess the adherence to MeDi and MIND diets, capturing associations with memory function and brain atrophy in healthy elders and individuals at increased AD dementia risk, making it a valid alternative in settings with time constraints.
Chronotype and sensory-processing sensitivity: A cross-sectional survey
2023-04-25

Here we examined the possibility of a relationship of sensory processing sensitivity (SPS) with chronotype in a German-speaking sample of <i>N</i> = 1807 (1008 female, 799 male) with a mean age of 47.75 ± 14.41 y (range: 18-97 y). The data were collected using an anonymous online questionnaire (Chronotype: one item of the Morning-Evening-Questionnaire, as well as typical bedtimes on weekdays and weekends; SPS: German version of the three-factor model ; Big Five: NEO-FFI-30) between 21 and 27 April 2021. Results. We found morningness to correlate with the SPS facet low sensory threshold (LST), while eveningness correlated to aesthetic sensitivity (AES) and marginally significant to ease of excitation (EOE). Discussion: The results show that the correlations between chronotype and the Big Five personality traits are not consistent with the direction of the correlations between chronotype and the SPS facets. The reason for this could be different genes that are responsible for the individual traits influence each other differently depending on their expression.
Titration of oncogenic RAS alters senescent state and influences tumour initiation
2023-04-25

<title>Abstract</title> Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with pre-malignancy<sup>1-3</sup>. Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS-dose escalation models in vitro and in vivo, revealing a RAS-dose-driven non-linear continuum of downstream phenotypes. In a hepatocyte OIS model in vivo, where ectopic expression of NRAS<sup>G12V</sup> fails to induce tumours in part due to OIS-driven immune clearance<sup>4</sup>. scRNA-seq analyses reveal distinct hepatocyte clusters with typical OIS or progenitor-like features, corresponding to high- and intermediate-NRAS<sup>G12V</sup> levels, respectively. Remarkably, when titered down, NRAS<sup>G12V</sup>-expressing hepatocytes become immune-resistant, and develop tumours. Time-series monitoring at single-cell resolution identifies two distinct tumour types: early-onset aggressive undifferentiated and late-onset differentiated hepatocellular carcinoma (HCC). The molecular signature of each murine tumour type is associated with different progenitor features and enriched in distinct human HCC subclasses. Our results define the oncogenic dosage-driven OIS spectrum, reconciling the senescence and tumour initiation phenotypes in early tumorigenesis.
Neural Importance Sampling for Rapid and Reliable Gravitational-Wave Inference
2023-04-26

We combine amortized neural posterior estimation with importance sampling for fast and accurate gravitational-wave inference. We first generate a rapid proposal for the Bayesian posterior using neural networks, and then attach importance weights based on the underlying likelihood and prior. This provides (1) a corrected posterior free from network inaccuracies, (2) a performance diagnostic (the sample efficiency) for assessing the proposal and identifying failure cases, and (3) an unbiased estimate of the Bayesian evidence. By establishing this independent verification and correction mechanism we address some of the most frequent criticisms against deep learning for scientific inference. We carry out a large study analyzing 42 binary black hole mergers observed by LIGO and Virgo with the SEOBNRv4PHM and IMRPhenomXPHM waveform models. This shows a median sample efficiency of ≈10% (2 orders of magnitude better than standard samplers) as well as a tenfold reduction in the statistical uncertainty in the log evidence. Given these advantages, we expect a significant impact on gravitational-wave inference, and for this approach to serve as a paradigm for harnessing deep learning methods in scientific applications.
Adapting to noise distribution shifts in flow-based gravitational-wave inference
2023-04-26

Deep learning techniques for gravitational-wave parameter estimation have emerged as a fast alternative to standard samplers producing results of comparable accuracy. These approaches (e.g., DINGO) enable amortized inference by training a normalizing flow to represent the Bayesian posterior conditional on observed data. By conditioning also on the noise power spectral density (PSD) they can even account for changing detector characteristics. However, training such networks requires knowing in advance the distribution of PSDs expected to be observed, and therefore can only take place once all data to be analyzed have been gathered. Here, we develop a probabilistic model to forecast future PSDs, greatly increasing the temporal scope of DINGO networks. Using PSDs from the second LIGO-Virgo observing run (O2) plus just a single PSD from the beginning of the third (O3) we show that we can train a DINGO network to perform accurate inference throughout O3 (on 37 real events). We therefore expect this approach to be a key component to enable the use of deep learning techniques for low-latency analyses of gravitational waves.
Hypoxia Changes Energy Metabolism and Growth Rate in Non-Small Cell Lung Cancer Cells
2023-04-26

Hypoxia occurs in 80% of non-small cell lung carcinoma (NSCLC) cases, leading to treatment resistance. Hypoxia’s effects on NSCLC energetics are not well-characterized. We evaluated changes in glucose uptake and lactate production in two NSCLC cell lines under hypoxia in conjunction with growth rate and cell cycle phase distribution. The cell lines A549 (p53 wt) and H358 (p53 null) were incubated under hypoxia (0.1% and 1% O2) or normoxia (20% O2). Glucose and lactate concentrations in supernatants were measured using luminescence assays. Growth kinetics were followed over seven days. Cell nuclei were stained with DAPI and nuclear DNA content was determined by flow cytometry to determine cell cycle phase. Gene expression under hypoxia was determined by RNA sequencing. Glucose uptake and lactate production under hypoxia were greater than under normoxia. They were also significantly greater in A549 compared to H358 cells. Faster energy metabolism in A549 cells was associated with a higher growth rate in comparison to H358 cells under both normoxia and hypoxia. In both cell lines, hypoxia significantly slowed down the growth rate compared to proliferation under normoxic conditions. Hypoxia led to redistribution of cells in the different cycle phases: cells in G1 increased and the G2 population decreased. Glucose uptake and lactate production increase under hypoxia in NSCLC cells indicated greater shunting of glucose into glycolysis rather than into oxidative phosphorylation compared to normoxia, making adenosine triphosphate (ATP) production less efficient. This may explain the redistribution of hypoxic cells in the G1 cell cycle phase and the time increase for cell doubling. Energy metabolism changes were more prominent in faster-growing A549 cells compared to slower-growing H358 cells, indicating possible roles for the p53 status and inherent growth rate of different cancer cells. In both cell lines, genes associated with cell motility, locomotion and migration were upregulated under chronic hypoxia, indicating a strong stimulus to escape hypoxic conditions.
Heart rate variability covaries with amygdala functional connectivity during voluntary emotion regulation
2023-04-26

The Neurovisceral Integration Model posits that shared neural networks support the effective regulation of emotions and heart rate, with heart rate variability (HRV) serving as an objective, peripheral index of prefrontal inhibitory control. Prior neuroimaging studies have predominantly examined both HRV and associated neural functional connectivity at rest, as opposed to contexts that require active emotion regulation. The present study sought to extend upon previous resting-state functional connectivity findings, examining task-related HRV and corresponding amygdala functional connectivity during a cognitive reappraisal task. Seventy adults (52 older and 18 younger adults, 18-84 years, 51% male) received instructions to cognitively reappraise negative affective images during functional MRI scanning. HRV measures were derived from a finger pulse signal throughout the scan. During the task, younger adults exhibited a significant inverse association between HRV and amygdala-medial prefrontal cortex (mPFC) functional connectivity, in which higher task-related HRV was correlated with weaker amygdala-mPFC coupling, whereas older adults displayed a slight positive, albeit non-significant correlation. Furthermore, voxelwise whole-brain functional connectivity analyses showed that higher task-based HRV was linked to weaker right amygdala-posterior cingulate cortex connectivity across older and younger adults, and in older adults, higher task-related HRV correlated positively with stronger right amygdala-right ventrolateral prefrontal cortex connectivity. Collectively, these findings highlight the importance of assessing HRV and neural functional connectivity during active regulatory contexts to further identify neural concomitants of HRV and adaptive emotion regulation.
Stiba‐, Arsa‐ and Phosphastannenes: Syntheses and Reactivities
2023-04-26

Abstract A facile synthesis for unprecedented stibastannene ( 10 ) featuring a Sn=Sb‐double bond together with the homologous arsa‐ ( 9 ) and phosphastannenes ( 8 ) is presented. Chloride abstraction from respective stannyl pnictinidenes [E=P ( 5 ), As ( 6 ), Sb ( 7 )], which were made accessible by reduction of ECl 3 addition products at an intramolecular phosphine‐stabilized stannylene, gave the pnictastannenes in moderate yields. The pnictastannenes coordinate Pd(PPh 3 ) 2 fragments ( 12 – 14 ) and the phosphastannene forms also a nickel coordination compound with the Ni(PPh 3 ) 2 ‐fragment ( 11 ). 2,3‐Dimethylbutadiene shows a [2+4]‐cycloaddition ( 15 – 17 ) in reaction with the pnictastannenes ( 8 – 10 ). Products of a [2+2]‐addition ( 18 , 19 ) were isolated as the phosphaalkyne reaction products for 8 and 9 . Addition of an O−H bond at the Sn=P‐bond was found in reaction of water with phosphastannene 8 . Reaction with ammonia afforded the NH 3 ‐adducts ( 21 – 23 ) at the tin atom for pnictastannenes 8 – 10 . Only in the case of the arsastannene an azide reaction product featuring a three membered Sn−As−N‐ring was obtained.