julilili42/papers huggingface dataset:
The role of relevance, competence, and priors for scalar inferences
2023-01-27

Although it is often assumed that the natural language expressions 'some' and 'or' are interpreted according to their first-order logic counterparts, in certain contexts, they receive a narrower interpretation: 'some' is strengthened to 'some, but not all', and 'or' to 'A or B, but not both'. This process is typically explained as an instance of scalar inference. To test this scalar implicature hypothesis, we collect experimental evidence for the effects and interactions of three factors that should affect the robustness of the scalar inferences of 'some' and 'or': the relevance of the stronger alternative, the speaker's competence about the alternative, and the prior probability that the alternative is true. We find that the interpretation of both triggers was affected by speaker competence, but only 'some' was also affected by prior probability, while relevance did not affect either trigger. Ultimately, our results suggest that the interdependence of the three factors is more complex than just the sum of their effects.
Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
2023-01-27

Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.
Ricci flow on surfaces along the standard lightcone in the $$3+1$$-Minkowski spacetime
2023-01-27

Abstract Identifying any conformally round metric on the 2-sphere with a unique cross section of the standard lightcone in the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>3</mml:mn> <mml:mo>+</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:math> -Minkowski spacetime, we gain a new perspective on 2 d -Ricci flow on topological spheres. It turns out that in this setting, Ricci flow is equivalent to a null mean curvature flow first studied by Roesch–Scheuer along null hypersurfaces. Exploiting this equivalence, we can translate well-known results from 2 d -Ricci flow first proven by Hamilton into a full classification of the singularity models for null mean curvature flow in the Minkowski lightcone. Conversely, we obtain a new proof of Hamilton’s classical result using only the maximum principle.
Transparency in the processing of temporal ambiguity: The case of embedded tense
2023-01-27

We report the results of one acceptability rating study and two self-paced reading studies on the form-meaning mismatch in the interpretation of past-under-past in complement clauses in English. Across the three experiments, we find an off-line and on-line preference for the backward-shifted interpretation, in line with predictions of the structural approach to the ambiguity when assuming a processing preference for morphological transparent interpretation.
Reading times show effects of contextual complexity and uncertainty in comprehension of German universal quantifiers
2023-01-27

We report three experiments, in which we combined self-paced reading with picture-sentence verification to test how reading times are affected by meaning-related processes. In particular, we investigated German sentences containing the universal quantifier alle (“all”) and examined how restrictive processes incrementally interact with other aspects of quantifier meaning, comparably to previous studies using other methods. Our results show that reading times were sensitive towards a match between context and sentence meaning and also towards an interaction between picture complexity and task demands. The results also point to the need for integrated processing models that combine refined notions of the relation between memory and expectations, on the one hand, with assumptions about adaptive processes and about representations involved in compositional interpretation, on the other.
Neopragmatic Reflections on Coastal Land Loss and Climate Change in Louisiana in Light of Popper’s Theory of Three Worlds
2023-01-28

This paper addresses the social resonances to the complex causes, effects, and feedback of land loss in southern Louisiana, particularly with respect to the region’s vulnerability to the impacts of anthropogenic climate change, especially against the backdrop of the consequences and side effects of the resident petrochemical industry. Using empirical findings from an online discussion about coastal land loss and talks to people in Louisiana, the different perceptions of coastal land loss of affected and not-affected people become apparent. As a result of the high complexity of the topic, a meta-theoretical framing by neopragmatism, as well as an analytical framing based on Popper’s theory of three worlds, is provided.
No home‐field advantage in litter decomposition from the desert to temperate forest
2023-01-28

Abstract Litter decomposition rates are determined by the interplay of climate, decomposer organisms and litter quality. It has been suggested that the decomposer community may be locally adapted to litter quality, providing a home‐field advantage (HFA) resulting in accelerated decomposition of local compared to non‐local litter, after accounting for decomposition differences due to litter quality and the functional capacity of microorganisms. Although widely tested in forests, this hypothesis remains controversial and lacks support of its generality across climates. We therefore tested the HFA hypothesis for litter decomposition in four contrasting ecosystems along an extensive climatic gradient in Chile, using a translocation experiment involving litter from 20 species. In addition to comparing mass loss, we adopted a novel way to disentangle decomposer effects from climate effects, based on loss rates of elements that are actively released from the litter by decomposers during its breakdown versus elements that are simply leached by precipitation. We used the ratios of nitrogen and potassium losses (N/K loss) and phosphorus and potassium losses (P/K loss) to unravel the relative role of microbial breakdown (N and P loss) versus physical leaching (K loss) along the climate gradient. Thus, at each site, we tested whether litter mass loss, N/K loss and P/K loss presented an additional loss due to a HFA for local compared to non‐local litter. Across a wide range of environments and litter types, our findings unequivocally contradicted the HFA hypothesis. We observed no significantly positive HFA along the gradient; however, litter quality and the general ability of the decomposer community influenced litter decomposition much more strongly than origin or location of the litter. Our study questions the applicability of the HFA for litter decomposition and calls for more studies that include a large range of climatic conditions to understand the context‐dependency of HFA. Read the free Plain Language Summary for this article on the Journal blog.
Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19
2023-01-28

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease’s catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.
Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients With Advanced Skin Cancers—Emerging Strategies for Clinical Management
2023-01-28

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.
CAR-T Cell Therapy and the Gut Microbiota
2023-01-28

Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects.
Evaluating Effects of Remotely Sensed Neighborhood Crowding and Depth-to-Water on Tree Height Growth
2023-01-28

Previous research on the effects of neighborhood crowding and soil moisture on tree height growth have been limited by time-consuming and sometimes inaccurate ground-based measurements of tree height. Recent developments in unmanned aerial vehicles (UAVs) allow detailed 3D point clouds of the canopy surface to be generated at relatively low cost. Using UAV-derived point clouds, we obtained height measurements of 4386 trees for the years 2019 and 2021. We also calculated four neighborhood crowding indices and a topography-based moisture index (depth-to-water) for these trees. Using initial tree height, neighborhood crowding indices and the depth-to-water index, we developed Bayesian hierarchical models to predict height growth for three tree species (Picea glauca (white spruce), Populus tremoluides (trembling aspen) and Pinus contorta (lodgepole pine)) across different stands. Bayes-R2 values of the final models were highest for white spruce (35%) followed by trembling aspen (28%) and lodgepole pine (25%). Model outputs showed that the effect of crowding and depth-to-water on height growth are limited and species-dependent, adding a maximum of 7% to the Bayes-R2 metric. Comparing different neighborhood crowding indices revealed that no index is clearly superior to others across all three species, as different neighborhood crowding indices resulted in only minor differences in model performance. While height growth can be partially explained by aerially derived neighborhood crowding indices and the depth-to-water index, future studies should focus on identifying relevant site characteristics to predict tree growth with greater accuracy.
Exploring Replay
2023-01-28

Exploration is vital for animals and artificial agents who face uncertainty about their environments due to initial ignorance or subsequent changes. Their choices need to balance exploitation of the knowledge already acquired, with exploration to resolve uncertainty [1, 2]. However, the exact algorithmic structure of exploratory choices in the brain still remains largely elusive. A venerable idea in reinforcement learning is that agents can plan appropriate exploratory choices offline, during the equivalent of quiet wakefulness or sleep. Although offline processing in humans and other animals, in the form of hippocampal replay and preplay, has recently been the subject of highly successful modelling [3–5], existing methods only apply to known environments. Thus, they cannot predict exploratory replay choices during learning and/or behaviour in dynamic environments. Here, we extend the theory of Mattar &amp; Daw [3] to examine the potential role of replay in approximately optimal exploration, deriving testable predictions for the patterns of exploratory replay choices in a paradigmatic spatial navigation task. Our modelling provides a normative interpretation of the available experimental data suggestive of exploratory replay. Furthermore, we highlight the importance of sequence replay, and license a range of new experimental paradigms that should further our understanding of offline processing.
In Silico Targeting of Fascin Protein for Cancer Therapy: Benchmarking, Virtual Screening and Molecular Dynamics Approaches
2023-01-29

Fascin is an actin-bundling protein overexpressed in various invasive metastatic carcinomas through promoting cell migration and invasion. Therefore, blocking Fascin binding sites is considered a vital target for antimetastatic drugs. This inspired us to find new Fascin binding site blockers. First, we built an active compound set by collecting reported small molecules binding to Fascin’s binding site 2. Consequently, a high-quality decoys set was generated employing DEKOIS 2.0 protocol to be applied in conducting the benchmarking analysis against the selected Fascin structures. Four docking programs, MOE, AutoDock Vina, VinaXB, and PLANTS were evaluated in the benchmarking study. All tools indicated better-than-random performance reflected by their pROC-AUC values against the Fascin crystal structure (PDB: ID 6I18). Interestingly, PLANTS exhibited the best screening performance and recognized potent actives at early enrichment. Accordingly, PLANTS was utilized in the prospective virtual screening effort for repurposing FDA-approved drugs (DrugBank database) and natural products (NANPDB). Further assessment via molecular dynamics simulations for 100 ns endorsed Remdesivir (DrugBank) and NANPDB3 (NANPDB) as potential binders to Fascin binding site 2. In conclusion, this study delivers a model for implementing a customized DEKOIS 2.0 benchmark set to enhance the VS success rate against new potential targets for cancer therapies.
Tire and Road Wear Particle-Containing Sediments with High Organic Content Impact Behavior and Survival of Chironomid Larvae (Chironomus riparius)
2023-01-29

Tire and road wear particles (TRWP), which contribute significantly to microplastic emission, are receiving more attention, but details about particle composition, translocation from source to sink, and particularly the possible effects on ecosystems are largely unknown. We examined the influence of native TRWP-containing sediments from two settling ponds on the mortality and behavior of the aquatic larvae of Chironomus riparius. Both sediments, whether pure or mixed with different proportions of quartz sand and suspended in water, led to increased mortalities with increasing concentrations and were shown to be oxygen consuming. Artificial aeration significantly reduced larval mortality in both sediments. Chironomid larvae show high tolerance to anoxic and polluted environments due to physiological and behavioral adaptations, such as the construction of vertical sediment tubes (chimneys), in which they create oxic compartments. A significant correlation was found between the proportion of contaminated sediment and the number of chimneys: the more contaminated sediment, the fewer chimneys were constructed. The number of chimneys per surviving larva decreased with an increased proportion of contaminated sediment in parallel to increased larval mortality. We hypothesize that contents of these sediments negatively impact the larvae’s ability to survive at low oxygen concentrations due to impairments of essential behavioral and physiological processes.
Arginine‐stimulated copeptin in children and adolescents
2023-01-30

Abstract Objective Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide (AVP) from the neurohypophysis. Its stability makes it a perfect candidate for the endocrine approach in the diagnosis of AVP deficiency (AVPD; cranial diabetes insipidus; CDI). However, pediatric reference values are lacking. Design and Patients This is a monocentric retrospective analysis of donated residual serum samples from 72 children and adolescents who underwent arginine or growth hormone‐releasing hormone‐arginine stimulation to test GH secretory capacity from 2018 to 2022. Measurements Copeptin was measured in baseline, 30‐, and 60‐min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. Results Of the 72 patients, 4 suffered from complete AVPD (CDI). The baseline level of copeptin in the 68 non‐AVPD (non‐CDI) patients was highly variable (range: 1.3–44.4 pmol/L). The increase after arginine was moderate (30 min range: 1.6–40.4 pmol/L). The median baseline and peak copeptin levels were 5.6 and 8.0 pmol/L, respectively. The 2.5th percentile of the baseline and peak values of copeptin were 2.1 and 3.3 pmol/L, respectively. The increase and peak value of copeptin were inversely related to age ( R = −.405; p = .011, and R = −.335; p = .0072, respectively) but not to gender, body mass index (standard deviation score) or GH secretion. In the four patients with AVPD (CDI), baseline or stimulated copeptin was below the 2.5th percentile of non‐AVPD (non‐CDI) patients. Conclusions Stimulated copeptin is a promising parameter for the differential diagnosis of polyuria‐polydipsia syndrome. However, the low copeptin increase after arginine and the high limit of quantification of the assay are problematic for use in paediatrics.
Vegetation and climate change at the southern margin of the Neo-Tethys during the Cenomanian (Late Cretaceous): Evidence from Egypt
2023-01-30

Changes in terrestrial vegetation during the mid-Cretaceous and their link to climate and environmental change are poorly understood. In this study, we use plant macrofossils and analysis of fossil pollen and spores from the Western Desert, Egypt, to assess temporal changes in plant communities during the Cenomanian. The investigated strata have relatively diverse sporomorph assemblages, which reflect the nature of parent vegetation. Specifically, the palynofloras represent ferns, conifers, monosulcate pollen producers, Gnetales, and a diverse group of angiosperms. Comparisons of both, dispersed palynoflora and plant macrofossils reveal different characteristics of the palaeoflora owing to a plethora of taphonomical and ecological biases including the depositional environment, production levels, and discrepancies between different plant organs. A combination of detailed records of sporomorphs, leaves, and charcoal from the studied successions provide new understandings of the palaeoclimate and palaeogeography during the Cenomanian and Albian-Cenomanian transition in Egypt. The mixed composition of the palynofloral assemblages reflects the presence of different depositional situations with a weak marine influence, as evidenced by a minor dinoflagellate cysts component. The local vegetation comprised various categories including herbaceous groups including ferns and eudicots, fluvial, open environments, and xeric arboreal communities dominated by Cheirolepidiaceae and perhaps including drought- and/or salt-tolerating ferns (Anemiaceae) and other gymnosperms (Araucariaceae, Ginkgoales, Cycadales, and Gnetales) as well as angiosperms. The presence of riparian and freshwater wetland communities favouring aquatic and/or hygrophilous ferns (of Salviniaceae and Marsileaceae), is noted. The wide variation of depositional settings derived from the palynological data may be attributed to a prevalent occurrence of producers in local vegetation during the early Cenomanian of Egypt. For the purpose of this work on the studied Bahariya Formation and its equivalent rock units, where iconic dinosaurs and other fossil fauna roamed, we attempt to improve the understanding of Egypt’s Cenomanian climate, which is reconstructed as generally warm and humid punctuated by phases of considerably drier conditions of varying duration.
The social, emotional, and behavioral skill antecedents to college students' volunteering during theCOVID‐19 pandemic
2023-01-30

Abstract The disruptions to community functioning caused by the COVID‐19 pandemic spurred individuals to action. This empirical study investigated the social, emotional, and behavioral (SEB) skill antecedents to college students' volunteering during the COVID‐19 pandemic ( N = 248, M age = 20.6). We assessed eight SEB skills at the onset of a volunteering program, and students' volunteer hours were assessed 10‐weeks later. Approximately 41.5% of the sample did not complete any volunteer hours. Higher levels of perspective taking skill, abstract thinking skill, and stress regulation were associated with more time spent volunteering. These results suggest that strength in particular SEB skills can prospectively predict prosocial civic behaviors.