julilili42/papers huggingface dataset:
Solid tumor-on-chip model for efficacy and safety assessment of CAR-T cell therapy
2023-07-15

ABSTRACT The non-clinical assessment of CAR-T cells demands innovative models that are capable of predicting safety and efficacy in the clinical setting. Here, we present a novel solid tumor-on-chip model that allows CAR-T cell perfusion and integrates the vasculature and tumor lesions to recapitulate key events of CAR-T cell performance including extravasation, tumor infiltration and cytokine release. We assessed CAR-T cells targeting the ROR1 antigen against tumor aggregates that were derived from a breast cancer cell line and primary breast cancer organoids. The data show the temporal kinetic of ROR1 CAR-T cell migration and expansion, lytic activity and cytokine production over the course of 8 days, and reveal a correlation between anti-tumor efficacy and ROR1 antigen density on tumor cells. CAR-modified T cells extravasated faster, infiltrated tumor lesions stronger, persisted longer and in higher numbers than non-CAR modified T cells. Intriguingly, we detected cytokine release levels and kinetics typically observed in patients who developed cytokine release syndrome, and administered dasatinib as a pharmacologic OFF switch to control this inflammatory response. The data illustrate the ability of this tumor-on-chip platform to assess parameters associated withherapeutic outcome and the potential to aid in patient stratification and monitoring of CAR-T cell therapy.
Processing references in context: when the polar bear does not meet a polar bear
2023-07-15

Abstract Discourse understanding is hampered when missing or conflicting context information is given. In four experiments, we investigated what happens (a) when the definite determiner “the,” which presupposes existence and uniqueness, does not find a unique referent in the context or (b) when the appropriate use of the indefinite determiner is violated by the presence of a unique referent (Experiment 1 and Experiment 2). To focus on the time-course of processing the uniqueness presupposition of the definite determiner, we embedded the determiner in different sentence structures and varied the context (Experiment 3 and Experiment 4). Reading time served as an index of processing difficulty in a word-by-word self-paced reading task and acceptability judgments provided hints for a possible repair of a presupposition violation. Our results showed that conflicting and missing context information lowered acceptability ratings and was associated with prolonged reading times. The pattern of results differed depending on the nature of the presupposition (Experiments 1 and 2) and whether supplementing missing context information was possible (Experiment 3 and Experiment 4). Our findings suggest that different cognitive processes come into play when interpreting presuppositions in order to get a meaningful interpretation of a discourse.
Mod2Panel: A Design Framework for Model-Based Automated Generation of Interactive Panels
2023-07-15

A panel is an event-centric starting point for implementing a model-based interactive system. The design and construction of an interactive panel involve deciding what information to display, how to display it, and ways to implement the design intent to produce an interactive panel. Traditionally, the design of panels has been implicit in the deployed applications, rather than explicitly considered as digital artifacts. In addition, users must realize this implicit design manually by coding or configuring it on programming platforms, resulting in hampered and time-consuming control and analysis. Besides, current tools do not have a unified generation mechanism, which makes it difficult for cooperation. In this paper, we propose a unified framework Mod2Panel, which enables users to draw their interactive panel designs as models and can automatically generate interactive panels from these models. The models are described in a modeling language that involves structures, behaviors, layout, and parameters. Mod2Panel also provides a GUI-assisted editor for customization to fine-tune the generated panels and update their associated models. With the capabilities of Mod2Panel, users can unify prototyping, generation and deployment in this framework for purposes of operation and control. We evaluate its effectiveness and efficiency in applied case studies on complex control systems and system modeling, in which Mod2Panel successfully generates interactive panels to support control monitoring and system-level analysis. The operations in the generated panel systems demonstrate the effectiveness of Mod2Panel for real-world scenarios.
Potential of UAV-Based Pattern Classification with Convolutional Neural Network on Moderate/Low Quality UAV Data
2023-07-16

This work serves as demonstrator, how low/medium quality UAV data can be integrated for agricultural pattern classification with convolutional neural network (CNN). The study also illustrates the potential sources of error in spectral and texture information that arise during image acquisition and processing, which can be improved during image processing and correct choice of mosaicking parameters.CNN classification of six agricultural patterns of interest (weed infested area, dry and vital crop area, dry and vital lodged crop area, bare soil area) of corn, rapeseed, winter wheat and spring barley fields. The performance of the classification is assessed on images with different units (reflectance and DN) and images with different sun lightening conditions, shadows and 'blur' effects (moderate/low quality data).
Antarctic Bedmap data: Findable, Accessible, Interoperable, and Reusable (FAIR) sharing of 60 years of ice bed, surface, and thickness data
2023-07-17

Abstract. One of the key components of this research has been the mapping of Antarctic bed topography and ice thickness parameters that are crucial for modelling ice flow and hence for predicting future ice loss and the ensuing sea level rise. Supported by the Scientific Committee on Antarctic Research (SCAR), the Bedmap3 Action Group aims not only to produce new gridded maps of ice thickness and bed topography for the international scientific community, but also to standardize and make available all the geophysical survey data points used in producing the Bedmap gridded products. Here, we document the survey data used in the latest iteration, Bedmap3, incorporating and adding to all of the datasets previously used for Bedmap1 and Bedmap2, including ice bed, surface and thickness point data from all Antarctic geophysical campaigns since the 1950s. More specifically, we describe the processes used to standardize and make these and future surveys and gridded datasets accessible under the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles. With the goals of making the gridding process reproducible and allowing scientists to re-use the data freely for their own analysis, we introduce the new SCAR Bedmap Data Portal (https://bedmap.scar.org, last access: 1 March 2023) created to provide unprecedented open access to these important datasets through a web-map interface. We believe that this data release will be a valuable asset to Antarctic research and will greatly extend the life cycle of the data held within it. Data are available from the UK Polar Data Centre: https://data.bas.ac.uk (last access: 5 May 2023​​​​​​​). See the Data availability section for the complete list of datasets.
A Means-End Account of Explainable Artificial Intelligence
2023-07-17

Abstract Explainable artificial intelligence (XAI) seeks to produce explanations for those machine learning methods which are deemed opaque. However, there is considerable disagreement about what this means and how to achieve it. Authors disagree on what should be explained (topic), to whom something should be explained (stakeholder), how something should be explained (instrument), and why something should be explained (goal). In this paper, I employ insights from means-end epistemology to structure the field. According to means-end epistemology , different means ought to be rationally adopted to achieve different epistemic ends. Applied to XAI, different topics, stakeholders, and goals thus require different instruments. I call this the means-end account of XAI. The means-end account has a descriptive and a normative component: on the one hand, I show how the specific means-end relations give rise to a taxonomy of existing contributions to the field of XAI; on the other hand, I argue that the suitability of XAI methods can be assessed by analyzing whether they are prescribed by a given topic, stakeholder, and goal.
Non-shared coding of observed and executed actions prevails in macaque ventral premotor mirror neurons
2023-07-17

According to the mirror mechanism the discharge of F5 mirror neurons of a monkey observing another individual performing an action is a motor representation of the observed action that may serve to understand or learn from the action. This hypothesis, if strictly interpreted, requires mirror neurons to exhibit an action tuning that is shared between action observation and execution. Due to insufficient data it remains contentious if this requirement is met. To fill in the gaps, we conducted an experiment in which identical objects had to be manipulated in three different ways in order to serve distinct action goals. Using three methods, including cross-task classification, we found that at most time points F5 mirror neurons did not encode observed actions with the same code underlying action execution. However, in about 20% of neurons there were time periods with a shared code. These time periods formed a distinct cluster and cannot be considered a product of chance. Population classification yielded non-shared coding for observed actions in the whole population, which was at times optimal and consistently better than shared coding in differentially selected subpopulations. These results support the hypothesis of a representation of observed actions based on a strictly defined mirror mechanism only for small subsets of neurons and only under the assumption of time-resolved readout. Considering alternative concepts and recent findings, we propose that during observation mirror neurons represent the process of a goal pursuit from the observer’s viewpoint. Whether the observer’s goal pursuit, in which the other’s action goal becomes the observer’s action goal, or the other’s goal pursuit is represented remains to be clarified. In any case, it may allow the observer to use expectations associated with a goal pursuit to directly intervene in or learn from another’s action.
Zooming out the microscope on cumulative cultural evolution: ‘Trajectory B’ from animal to human culture
2023-07-17

Abstract It is widely believed that human culture originated in the appearance of Oldowan stone-tool production (circa 2.9 Mya) and a primitive but effective ability to copy detailed know-how. Cumulative cultural evolution is then believed to have led to modern humans and human culture via self-reinforcing gene-culture co-evolution. This outline evolutionary trajectory has come to be seen as all but self-evident, but dilemmas have appeared as it has been explored in increasing detail. Can we attribute even a minimally effective know-how copying capability to Oldowan hominins? Do Oldowan tools really demand know-how copying? Is there any other evidence that know-how copying was present? We here argue that this account, which we refer to as “Trajectory A”, may be a red herring, and formulate an alternative “Trajectory B” that resolves these dilemmas. Trajectory B invokes an overlooked group-level channel of cultural inheritance (the Social Protocell) whereby networks of cultural traits can be faithfully inherited and potentially undergo cumulative evolution, also when the underpinning cultural traits are apelike in not being transmitted via know-how copying (Latent Solutions). Since most preconditions of Trajectory B are present in modern-day Pan , Trajectory B may even have its roots considerably before Oldowan toolmaking. The cumulative build-up of networks of non-cumulative cultural traits is then argued to have produced conditions that both called for and afforded a gradual appearance of the ability to copy know-how, but considerably later than the Oldowan.
RX J0440.9+4431: another supercritical X-ray pulsar
2023-07-17

ABSTRACT In the beginning of 2023, the Be transient X-ray pulsar RX J0440.9+4431 underwent a first-ever giant outburst observed from the source peaking in the beginning of February and reaching peak luminosity of ≈4.3 × 1037 erg s−1. Here, we present the results of a detailed spectral and temporal study of the source based on NuSTAR, Swift, INTEGRAL, and NICER observations performed during this period and covering wide range of energies and luminosities. We find that both the pulse profile shape and spectral hardness change abruptly around ≈2.8 × 1037 erg s−1, which we associate with a transition to supercritical accretion regime and erection of the accretion column. The observed pulsed fraction decreases gradually with energy up to 20 keV (with a local minimum around fluorescence iron line), which is unusual for an X-ray pulsar, and then rises rapidly at higher energies with the pulsations significantly detected up to ≈120 keV. The broad-band energy spectra of RX J0440.9+4431 at different luminosity states can be approximated with a two-hump model with peaks at energies of about 10–20 and 50–70 keV previously suggested for other pulsars without additional features. In particular, an absorption feature around 30 keV previously reported and interpreted as a cyclotron line in the literature appears to be absent when using this model, so the question regarding the magnetic field strength of the neutron star remains open. Instead, we attempted to estimate field using several indirect methods and conclude that all of them point to a relatively strong field of around B ∼ 1013 G.
Effects of Online Teacher Professional Development on the Teacher, Classroom, and Student Level: A Meta-Analysis
2023-07-17

Teachers’ professional development is crucial for effective classroom practice. Due to its advantages, many teachers have participated in online professional development (OPD) in recent years. Numerous studies have investigated the effectiveness of OPD either on the teacher, their classroom, or the student level. However, a comprehensive meta-analysis of these studies is missing. This meta-analysis summarizes findings from 85 quantitative studies with a pre-posttest design. The results indicate large effects of OPD participation on the teacher level (d = 0.66), a medium to large effect on the classroom level (d = 0.59), and a small effect on the student level (d = 0.21). Additionally, we found that the core feature of PD activities, such as collective participation, was positively associated with the effect of the classroom level. Furthermore, we found that studies employing a control-group design reported significantly lower effect sizes on teacher-level outcomes than studies using a within-subject design. At the student level, studies with asynchronous OPD formats reported significantly smaller effect sizes than studies with synchronous OPD formats. Our results suggest that OPD can have substantial simultaneous effects on different school system levels and could be fostered more systematically to enhance school development and improvement processes.
Towards a logic for ‘because’
2023-07-17

Abstract This paper explores the connective ‘because’, based on the idea that ‘ C because A ’ implies the acceptance/truth of the antecedent A as well as of the consequent C , and additionally that the antecedent makes a difference for the consequent. To capture this idea of difference-making a ‘relevantized’ version of the Ramsey Test for conditionals is employed that takes the antecedent to be relevant to the consequent in the following sense: a conditional is true/accepted in a state <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>σ</mml:mi> </mml:math> just in case (i) the consequent is true/accepted when <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>σ</mml:mi> </mml:math> is revised by the antecedent and (ii) the consequent fails to be true/accepted when <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>σ</mml:mi> </mml:math> is revised by the antecedent’s negation. To extend this to a semantics for ‘because’, we add that (iii) the antecedent and (iv) the consequent are accepted/true in the state <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>σ</mml:mi> </mml:math> . We get metaphysical or doxastic interpretations of these clauses, depending on what we mean by a model and a state. We introduce several semantics known from suppositional conditionals, which we reinterpret for difference-making conditionals and ‘because’. We present a minimal logic for ‘because’ sentences and show how it can be extended in ways that parallel the hierarchy of extensions of the logic of suppositional conditionals. We establish correspondence results between axioms for ‘because’ and properties of states, and prove that the specified logics are sound with respect to the semantics.
How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World
2023-07-17

Objective: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment. Methods: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics. Results: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases. Conclusion: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases. Key Points: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.
Precise and efficient C-to-U RNA base editing with SNAP-CDAR-S
2023-07-18

Abstract Site-directed RNA base editing enables the transient and dosable change of genetic information and represents a recent strategy to manipulate cellular processes, paving ways to novel therapeutic modalities. While tools to introduce adenosine-to-inosine changes have been explored quite intensively, the engineering of precise and programmable tools for cytidine-to-uridine editing is somewhat lacking behind. Here we demonstrate that the cytidine deaminase domain evolved from the ADAR2 adenosine deaminase, taken from the RESCUE-S tool, provides very efficient and highly programmable editing when changing the RNA targeting mechanism from Cas13-based to SNAP-tag-based. Optimization of the guide RNA chemistry further allowed to dramatically improve editing yields in the difficult-to-edit 5′-CCN sequence context thus improving the substrate scope of the tool. Regarding editing efficiency, SNAP-CDAR-S outcompeted the RESCUE-S tool clearly on all tested targets, and was highly superior in perturbing the β-catenin pathway. NGS analysis showed similar, moderate global off-target A-to-I and C-to-U editing for both tools.
Model averaging of machine learning algorithms for digital soil mapping: A minimum variance framework
2023-07-18

In the digital soil mapping framework, machine learning (ML) algorithms are currently the most popular methods for the spatial prediction of soil properties. The fast developments of easy-to-use software implementations for a large panel of ML algorithms have encouraged comparison studies between algorithms, with the goal of ranking their performances and identifying the best ones among them. However, as no firm conclusions can be drawn about the best ML algorithm to be used in general, this suggests that combining a set of them could be a better approach. Numerous methods have been proposed to do so, most of them relying on a linear weighting of the individual algorithms. However, there are almost as many methods for linearly weighting ML algorithms as there are ML algorithms, thus leaving the problem unsolved. Moreover, these weighting methods are mostly used out-of-the-box, without paying a proper attention to the associated hypotheses. In this paper, we propose to address this issue by setting the problem in a more formal framework. Starting from classical hypotheses, it is shown how the benefit of averaging various ML algorithms can be estimated from their joint performances. Relying afterwards on the most commonly used linear weighting schemes, it is reminded that, as long as the performance metrics are based on mean square errors, the best averaging method is by essence the best linear (unbiased) predictor. Using a more general Bayesian framework, it is also shown that accounting for conditional biases when weighting ML algorithms is a key issue for obtaining improved predictions, and explicit formulas are proposed for that goal. Finally, these theoretical results are illustrated and discussed using a soil data set collected over an arid and semi-arid region in Iran where clay content, calcium carbonate equivalent, soil organic carbon and electrical conductivity were measured in topsoil samples.