julilili42/papers huggingface dataset:
BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS‐mutant melanoma cells: Insights into mode of action and resistance mechanisms
2023-12-11

Abstract About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS‐mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS‐mutant melanoma, providing an ideal backbone for combination treatments. In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS‐mutant melanoma cells using two‐ and three‐dimensional cell culture models as well as RNA sequencing analyses. Furthermore, NRAS‐mutant melanoma cells resistant to the three BRAFi/MEKi combinations were established to characterize the mechanisms contributing to their resistance. All BRAFi induced a stress response in the sensitive NRAS‐mutant melanoma cells thereby significantly enhancing the antiproliferative and proapoptotic activity of the MEKi analyzed. Furthermore, BRAFi/MEKi combinations upregulated immune relevant molecules, such as ICOS‐L, components of antigen‐presenting machinery and the “don't eat me signal” molecule CD47 in the melanoma cells. The BRAFi/MEKi‐resistant, NRAS‐mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen‐activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS‐mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS‐mutant melanoma.
Cluster-Based Approach Utilizing Optimally Tuned TD-DFT to Calculate Absorption Spectra of Organic Semiconductor Thin Films
2023-12-11

The photophysics of organic semiconductor (OSC) thin films or crystals has garnered significant attention in recent years since a comprehensive theoretical understanding of the various processes occurring upon photoexcitation is crucial for assessing the efficiency of OSC materials. To date, research in this area has relied on methods using Frenkel-Holstein Hamiltonians, calculations of the GW-Bethe-Salpeter equation with periodic boundaries, or cluster-based approaches using quantum chemical methods, with each of the three approaches having distinct advantages and disadvantages. In this work, we introduce an optimally tuned, range-separated time-dependent density functional theory approach to accurately reproduce the total and polarization-resolved absorption spectra of pentacene, tetracene, and perylene thin films, all representative OSC materials. Our approach achieves excellent agreement with experimental data (mostly ≤0.1 eV) when combined with the utilization of clusters comprising multiple monomers and a standard polarizable continuum model to simulate the thin-film environment. Our protocol therefore addresses a major drawback of cluster-based approaches and makes them attractive tools for OSC investigations. Its key advantages include its independence from external, system-specific fitting parameters and its straightforward application with well-known quantum chemical program codes. It demonstrates how chemical intuition can help to reduce computational cost and still arrive at chemically meaningful and almost quantitative results.
Technology, Power, and Social Inclusion: Afghan Refugee Women’s Interaction with ICT in Germany
2023-12-11

Afghan refugee women settle in Germany to escape persecution by militant groups and social marginalization in Afghanistan, among other things. They face challenges in Germany, such as language barriers, demanding bureaucratic requirements from German administrations, and discrimination. Academic and public discourses promote the information and communication technologies (ICT)-enabled social inclusion of refugees into the host society. ICT is widely seen as an essential tool to support refugees. Against this backdrop, this paper presents a focus group study with 14 Afghan refugee women in Germany to understand their experiences with technology: How do Afghan refugee women in Germany experience ICT? What structural factors influence their interaction with technology? What are the design features in an application that can support their settlement in Germany? This paper uses a critical perspective inspired by Black feminist theory to foreground the dynamics of power in Afghan refugee women’s experiences with ICT. The analysis reveals significant barriers to the participation of Afghan refugee women in German digital society, like digital illiteracy and the need for safety and privacy, making accessing technology difficult. Designs of ICT that may benefit Afghan women offer audio messages instead of text, real-time assistance, intuitive commands, and registration without an email address. Apart from the analysis of Afghan refugee women’s interaction with technology in German society, this paper reflects on the German migration management infrastructure and its potential to adapt more to the communication practices of refugees, including offering in-person services for Afghan refugee women.
Highly Transparent, Yet Photoluminescent: 2D CdSe/CdS Nanoplatelet‐Zeolitic Imidazolate Framework Composites Sensitive to Gas Adsorption
2023-12-11

Abstract In this work, thin composite films of zeolitic imidazolate frameworks (ZIFs) and colloidal two‐dimensional (2D) core‐crown CdSe/CdS nanoplatelet (NPL) emitters with minimal scattering are formed by a cycled growth method and yield highly transparent coatings with strong and narrow photoluminescence of the NPLs at 546 nm (FWHM: 25 nm) in a solid‐state composite structure. The porous ZIF matrix acts as functional encapsulation for the emitters and enables the adsorption of the guest molecules water and ethanol. The adsorption and desorption of the guest molecules is then characterized by a reversable photoluminescence change of the embedded NPLs. The transmittance of the composite films exceeds the values of uncoated glass at visible wavelengths where the NPL emitters show no absorption (&gt;540 nm) and renders them anti‐reflective coatings. At NPL absorption wavelengths (440–540 nm), the transmittance of the thin composite film‐coated glass lies close to the transmittance of uncoated glass. The fast formation of innovative, smooth NPL/ZIF composite films without pre‐polymerizing the colloidal 2D nanostructures first provides a powerful tool toward application‐oriented photoluminescence‐based gas sensing.
Misleading But Not Fake: Measuring the Difference Between Manipulativeness Discernment and Veracity Discernment Using Psychometrically Validated Tests
2023-12-11

Misinformation continues to pose a substantial societal problem, but the measurement of misinformation susceptibility has often been done using non-validated tests. Furthermore, research shows that misleading content (implied misinformation) is much more common than outright false content (explicit misinformation). However, there is very little research on the predictors of belief in implied misinformation, and it is unknown if susceptibility to direct and implied misinformation are psychologically similar. To address these questions, we ran three preregistered studies (N 1 = 487, N 2 = 547, N 3 = 490) in which we developed and validated the 24-item and 12-item Manipulative Online Content Recognition Inventory (MOCRI), a test that measures a person’s ability to distinguish between misleading and neutral content. This test substantially outperforms other known predictors of misinformation susceptibility in terms of its predictive value for people’s ability to correctly identify many kinds of misleading content. We also show that susceptibility to misleading and false content are psychologically different from one another, although they are related. Finally, we show that people who score high on the MOCRI are much better than low MOCRI performers at discerning manipulative from non-manipulative statements (i.e., they have better “discernment”), but that this ability does not necessarily translate to better discernment in the quality of their sharing decisions, or their willingness to reply to manipulative vs. non-manipulative messages. Instead, people who are more resilient to being manipulated are lesslikely to share and respond to both manipulative and non-manipulative content.
Maize mutants in miR394-regulated genes show improved drought tolerance
2023-12-11

Abstract Water limitation represents one of the major threats to agricultural production, which often leads to drought stress and results in compromised growth, development and yield of crop species. Drought tolerance has been intensively studied in search for potential targets for molecular approaches to crop improvement. However, drought adaptive traits are complex and our understanding of the physiological and genetic basis of drought tolerance is still incomplete. The miR394-LCR pathway is a conserved regulatory module shown to participate in several aspects of plant growth and development, including stress response. Here we characterized the miR394 pathway in maize, which harbors two genetic loci producing an evolutionarily conserved mature zma-miR394 targeting two transcripts coding for F-Box proteins, named hereby ZmLCR1 and ZmLCR2. Arabidopsis plants overexpressing zma-MIR394B gene showed high tolerance to drought conditions, compared to control plants. Moreover, analysis of growth and development of single and double maize mutant plants in ZmLCR genes indicate that these mutations do not affect plant fitness when they grow in normal watering conditions, but mutants showed better survival than wild type plants under water deprivation conditions. This increased drought tolerance is based on a more efficient intrinsic water use, changes in root architecture and increased epicuticular wax content under water limiting conditions. Our results indicate that the miR394-regulated ZmLCR genes are involved in drought stress tolerance and are remarkable candidates for maize crop improvement.
Survivorship Program Including Long-Term Toxicities and Quality-of-Life Development Over Ten Years within a Randomized Phase-III Trial in Operable Stage III Non-Small-Cell Lung Cancer (ESPATUE)
2023-12-11

Abstract Purpose Over 40% stage-III non-small-cell lung cancer patients experience five-year survival following multimodality treatment. Little is known about relevant late toxicities and quality-of-life (QoL) ten years from diagnosis. Methods We invited long-term follow-up-patients from our randomized phase-III trial (Eberhardt et al., Journal of Clinical Oncology 2015) to participate within a structured survivorship program (SSP) including follow-up imaging, laboratory parameters, cardio-pulmonary investigations and long-term toxicity evaluations. QoL questionnaires at 10-years were compared to baseline and early follow-up on exploratory basis. Results Of 246 patients included, 161 evaluated potentially resectable after induction were randomized to definitive chemoradiation boost (A; 80) or definitive surgery (B; 81) (85 not randomized (C)). 31 of 37 patients (OS &gt; 10 yrs) agreed to the SSP (A:13, B:12, C:6). Significant long-term toxicities of 3°/4° were rarely observed (lung(FEV1) 3° A:0/9, B:1/6, C:0/5; 4° A:1/9, B:0/6, C:1/5; no 3°/4° cardiac toxicity, no 3°/4° chronic kidney disease, no 3°/4° polyneuropathy). A:5/12, B:1/10 and C:1/6 patients showed relevant nutritional disorders (obesity 3°). QoL analysis of both arms showed no relevant signals of worsening compared to earlier and baseline results. Mean QoL in SSP A: 56.41/100 pts., B: 64.39/100 pts., C: 59.72/100 pts. Conclusions Long-term surviving patients following definitive chemoradiation or surgery showed comparable long-term toxicities and QoL assessments. Most patients are in good clinical status. Implications for Cancer Survivors This is the first comprehensive SSP reported in stage-III NSCLC treated within a randomized multimodality trial and may serve as baseline information for physician and patient deciding for a treatment option.
Measuring Cognitive Ability in Children and Adolescents: Development and Validation of a New Test Battery for Working Memory Capacity
2023-12-11

Working memory capacity (WMC) measures for children are unsatisfying in terms of lack of operational continuity with measures for adolescents and adults. Thus, we developed and validated a multivariate WMC test battery that uses WMC paradigms that can be applied from 1st grade onwards. In Study 1, we developed child-contextualized WMC tests and investigated their psychometric properties (including gender differences) in n = 343 1st graders. In Study 2, we juxtaposed child-contextualized and decontextualized instantiations of our tasks in n = 379 5th to 10th graders. Child-contextualized tests were essentially equivalent to structurally identical, decontextualized WMC tests, and the battery correlated strongly with a multivariate measure of fluid intelligence. Across studies, we found support for good psychometric properties of the tests. The battery bridges the gap between child-specific and decontextualized WMC tests, is applicable for all ability levels, can be adapted easily in terms of difficulty and length.
Identification of novel genes including NAV2 associated with isolated tall stature
2023-12-12

Very tall people attract much attention and represent a clinically and genetically heterogenous group of individuals. Identifying the genetic etiology can provide important insights into the molecular mechanisms regulating linear growth. We studied a three-generation pedigree with five isolated (non-syndromic) tall members and one individual with normal stature by whole exome sequencing; the tallest man had a height of 211 cm. Six heterozygous gene variants predicted as damaging were shared among the four genetically related tall individuals and not present in a family member with normal height. To gain insight into the putative role of these candidate genes in bone growth, we assessed the transcriptome of murine growth plate by microarray and RNA Seq. Two ( Ift140, Nav2 ) of the six genes were well-expressed in the growth plate. Nav2 ( p -value 1.91E-62) as well as Ift140 ( p -value of 2.98E-06) showed significant downregulation of gene expression between the proliferative and hypertrophic zone, suggesting that these genes may be involved in the regulation of chondrocyte proliferation and/or hypertrophic differentiation. IFT140, NAV2 and SCAF11 have also significantly associated with height in GWAS studies. Pathway and network analysis indicated functional connections between IFT140 , NAV2 and SCAF11 and previously associated (tall) stature genes. Knockout of the all-trans retinoic acid responsive gene, neuron navigator 2 NAV2 , in Xenopus supports its functional role as a growth promotor. Collectively, our data expand the spectrum of genes with a putative role in tall stature phenotypes and, among other genes, highlight NAV2 as an interesting gene to this phenotype.
Radar internal reflection horizons from multisystem data reflect ice dynamic and surface accumulation history along the Princess Ragnhild Coast, Dronning Maud Land, East Antarctica
2023-12-12

Abstract Ice shelves, which regulate ice flow from the Antarctic ice sheet towards the ocean, are shaped by spatiotemporal patterns of surface accumulation, surface/basal melt and ice dynamics. Therefore, an ice dynamic and accumulation history are imprinted in the internal ice stratigraphy, which can be imaged by radar in the form of internal reflection horizons (IRHs). Here, IRHs were derived from radar data combined across radar platforms (airborne and ground-based) in coastal eastern Dronning Maud Land (East Antarctica), comprising three ice rises and adjacent two ice shelves. To facilitate interpretation of dominant spatiotemporal patterns of processes shaping the local IRH geometry, traced IRHs are classified into three different types (laterally continuous, discontinuous or absent/IRH-free). Near-surface laterally continuous IRHs reveal local accumulation patterns, reflecting the mean easterly wind direction, and correlate with surface slopes. Areas of current and past increased ice flow and internal deformation are marked by discontinuous or IRH-free zones, and can inform about paleo ice-stream dynamics. The established IRH datasets extend continent-wide mapping efforts of IRHs to an important and climatically sensitive ice marginal region of Antarctica and are ready for integration into ice-flow models to improve predictions of Antarctic ice drainage.
A new booid snake from the Eocene (Lutetian) Konservat-Lagerstätte of Geiseltal, Germany, and a new phylogenetic analysis of Booidea
2023-12-12

Abstract We describe two exceptionally preserved fossil snakes from the Eocene Konservat-Lagerstätte of Geiseltal, located in the state of Saxony-Anhalt, Germany. The two snake specimens, GMH LIX-3-1992 and GMH XXXVIII-20-1964, can be confidently identified as booids based on general morphology and were thus compared to other geographically and/or temporally close fossil booids. We found that GMH LIX-3-1992 is morphologically very similar to Eoconstrictor spinifer, also from Geiseltal, and to Eoconstrictor fischeri, from the middle Eocene of Messel, but differs from both in a number of cranial and vertebral features. Based on these differences we erect the new species Eoconstrictor barnesi sp. nov.; GMH XXXVIII-20-1964 is very similar to GMH LIX-3-1992 and the two differ only in features that are likely ontogenetic. Phylogenetic analyses of snakes using maximum parsimony and Bayesian inference on datasets inclusive of both morphological and molecular data consistently support a close affinity of E. barnesi to E. fischeri and E. spinifer. Our preferred phylogenetic hypothesis places the three species of Eoconstrictor in a clade that is sister to Neotropical Boidae, a result consistent with previous studies. The genus Eoconstrictor could provide an important calibration point for molecular clock studies of booids and snakes in general.
Calibration of the Timing Performance of GECAM-C
2023-12-12

Abstract As a new member of the Gravitational-wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) after GECAM-A and GECAM-B, GECAM-C (originally called HEBS), which was launched on board the SATech-01 satellite on 2022 July 27, aims to monitor and localize X-ray and gamma-ray transients from ∼6 keV to 6 MeV. GECAM-C utilizes a similar design to GECAM but operates in a more complex orbital environment. In this work, we utilize the secondary particles simultaneously produced by the cosmic-ray events on orbit and recorded by multiple detectors to calibrate the relative timing accuracy between all detectors of GECAM-C. We find the result is 0.1 μ s, which is the highest time resolution among all GRB detectors ever flown and very helpful in timing analyses such as minimum variable timescale and spectral lags, as well as in time delay localization. Besides this, we calibrate the absolute time accuracy using the one-year Crab Pulsar data observed by GECAM-C and Fermi’s Gamma-ray Burst Monitor, as well as GECAM-C and GECAM-B. The results are 2.02 ± 2.26 μ s and 5.82 ± 3.59 μ s, respectively. Finally, we investigate the spectral lag between the different energy bands of the Crab Pulsar observed by GECAM and the Gamma-ray Burst Monitor, which is ∼ −0.2 μ s keV −1 .
ER-anchored protein sorting controls the fate of two proteasome activators for intracellular organelle communication during proteotoxic stress
2023-12-12

Summary Proteotoxic stress, characterized by the accumulation of damaged proteins, poses a significant challenge to cellular homeostasis. To mitigate proteotoxicity eukaryotes employ the proteasome that is regulated by proteasome activators, e.g. transcription factors that promote gene expression of proteasome subunits. As proteotoxicity originates in different compartments, cells need to perceive signals from various locations. Understanding which components integrate signals to address proteotoxicity is essential to develop strategies to cope with proteotoxicity but remain elusive. Here, we identify that the proteasome autoregulatory feedback loop acts as a gatekeeper to facilitate the communication between nucleus and chloroplast. We reveal that the ER-anchored protein sorting system (ERAPS) controls the proteasomal degradation or nuclear translocation of proteasome activators NAC53 and NAC78. While both transcription factors activate the proteasome gene expression, they repress photosynthesis-associated nuclear genes during proteotoxicity through association with a conserved cis-element. Our data implicate a general trade-off between proteasome function and energy metabolism unravelling an unprecedented mechanism of how eukaryotic cells cope with proteotoxicity. Collectively, our discoveries provide a novel conceptual framework in which the proteasome autoregulatory feedback loop coordinates subcellular proteostasis and the trade-off between growth and defence.
Ion mobility in gas and liquid phases: How much orthogonality is obtained in capillary electrophoresis–ion mobility–mass spectrometry?
2023-12-12

Abstract Ion mobility–mass spectrometry (IM–MS) is an ever‐evolving tool to separate ions in the gas phase according to electrophoretic mobility with subsequent mass determination. CE is rarely coupled to IM–MS, possibly due to similar separation mechanisms based on electrophoretic mobility. Here, we investigate the orthogonality of CE and ion mobility (IM) by analyzing a complex peptide mixture (tryptic digest of HeLa proteins) with trapped ion mobility mass spectrometry (TIMS–MS). Using the nanoCEasy interface, excellent sensitivity was achieved by identifying thousands of peptides and achieving a peak capacity of 7500 (CE: 203–323 in a 150 cm long capillary, IM: 27–31). Plotting CE versus mass and CE versus (inverse) mobility, a clear grouping in curved striped patterns is observed according to the charge‐to‐size and mass‐to‐charge ratios. The peptide charge in the acidic background electrolyte can be estimated from the number of basic amino acids, with a few exceptions where neighboring effects reduce the positive charge. A surprisingly high orthogonality of CE and IM is observed, which is obviously caused by solvation effects leading to different charges and sizes in the liquid phase compared to the gas phase. A high orthogonality of CE and ion mobility is expected to be observed for other peptide samples as well as other substance classes, making CE–IM–MS a promising tool for various applications.