Miracle-dz/UniFAR-FTUs huggingface dataset:
A Multi-scale, Multi-region and Attention Mechanism-based Deep Learning Framework for Prediction of Grading in Hepatocellular Carcinoma.

BACKGROUND Histopathological grading is a significant risk factor for postsurgical recurrence in hepatocellular carcinoma (HCC). Preoperative knowledge of histopathological grading could provide instructive guidance for individualized treatment decision-making in HCC management. PURPOSE This study aims to develop and validate a newly proposed deep learning model to predict histopathological grading in HCC with improved accuracy. METHODS In this dual-center study, we retrospectively enrolled 384 HCC patients with complete clinical, pathological and radiological data. Aiming to synthesize radiological information derived from both tumor parenchyma and peritumoral microenvironment regions, a modeling strategy based on a multi-scale and multi-region dense connected convolutional neural network (MSMR-DenseCNNs) was proposed to predict histopathological grading using preoperative contrast enhanced computed tomography (CT) images. Multi-scale inputs were defined as three-scale enlargement of an original minimum bounding box in width and height by given pixels, which correspondingly contained more peritumoral analysis areas with the enlargement. Multi-region inputs were defined as three regions of interest (ROIs) including a squared ROI, a precisely delineated tumor ROI, and a peritumoral tissue ROI. The DenseCNN structure was designed to consist of a shallow feature extraction layer, dense block module, and transition and attention module. The proposed MSMR-DenseCNN was pretrained by the ImageNet dataset to capture basic graphic characteristics from the images and was retrained by the collected retrospective CT images. The predictive ability of the MSMR-DenseCNN models on triphasic images was compared with a conventional radiomics model, radiological model and clinical model. RESULTS MSMR-DenseCNN applied to the delayed phase (DP) achieved the highest area under the curve (AUC) of 0.867 in the validation cohort for grading prediction, outperforming those on the arterial phase (AP) and portal venous phase (PVP). Fusion of the results on triphasic images did not increase the predictive ability, which underscored the role of DP for grading prediction. Compared with a single-scale and single-region network, the DP-phase based MSMR-DenseCNN model remarkably raised sensitivity from 67.4% to 75.5% with comparable specificity of 78.6%. MSMR-DenseCNN on DP defeated conventional radiomics, radiological and clinical models, where the AUCs were correspondingly 0.765, 0.695 and 0.612 in the validation cohort. CONCLUSIONS The MSMR-DenseCNN modeling strategy increased the accuracy for preoperative prediction of grading in HCC, and enlightens similar radiological analysis pipelines in a variety of clinical scenarios in HCC management. This article is protected by copyright. All rights reserved.
The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes

Abstract In-depth analysis of the transcriptomes of several model organisms has revealed that genomes are pervasively transcribed, giving rise to an abundance of non-canonical and mainly antisense RNA polymerase II-derived transcripts that are produced from almost any genomic context. Pervasive RNAs are degraded by surveillance mechanisms, but the repertoire of proteins that control the fate of these non-productive transcripts is still incomplete. Trypanosomes are single-celled eukaryotes that show constitutive RNA polymerase II transcription and in which initiation and termination of transcription occur at a limited number of sites per chromosome. It is not known whether pervasive transcription exists in organisms with unregulated RNA polymerase II activity, and which factors could be involved in the process. We show here that depletion of RBP33 results in overexpression of ∼40% of all annotated genes in the genome, with a marked accumulation of sense and antisense transcripts derived from silenced regions. RBP33 loss does not result in a significant increase in chromatin accessibility. Finally, we have found that transcripts that increase in abundance upon RBP33 knockdown are significantly more stable in RBP33-depleted trypanosomes, and that the exosome complex is responsible for their degradation. Our results provide strong evidence that RBP33 dampens non-productive transcription in trypanosomes.
Combined spectral and speech features for pig speech recognition

The sound of the pig is one of its important signs, which can reflect various states such as hunger, pain or emotional state, and directly indicates the growth and health status of the pig. Existing speech recognition methods usually start with spectral features. The use of spectrograms to achieve classification of different speech sounds, while working well, may not be the best approach for solving such tasks with single-dimensional feature input. Based on the above assumptions, in order to more accurately grasp the situation of pigs and take timely measures to ensure the health status of pigs, this paper proposes a pig sound classification method based on the dual role of signal spectrum and speech. Spectrograms can visualize information about the characteristics of the sound under different time periods. The audio data are introduced, and the spectrogram features of the model input as well as the audio time-domain features are complemented with each other and passed into a pre-designed parallel network structure. The network model with the best results and the classifier were selected for combination. An accuracy of 93.39% was achieved on the pig speech classification task, while the AUC also reached 0.99163, demonstrating the superiority of the method. This study contributes to the direction of computer vision and acoustics by recognizing the sound of pigs. In addition, a total of 4,000 pig sound datasets in four categories are established in this paper to provide a research basis for later research scholars.
On time-irreversibility and other non-linear features in time series

Time-irreversibility, asymmetry of the distribution, and the occurrence of sudden bursts are considered, amongst others, as non-linear features in time series modeling. The implication is often made that time series showing these features must be analyzed using non-linear models. In contrast, this paper shows that time-irreversible asymmetric time series showing certain types of sudden bursts may be generated by linear models with adequate input sequences. Thus some non-linear time series features may be caused by the pattern in the input sequence rather than by non-linearity in the model. Examples are considered to illustrate the situation.
DDX17 helicase promotes resolution of R-loop-mediated transcription–replication conflicts in human cells

Abstract R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81–LIG4–ELL pathway for resolution of R-loop-mediated transcription–replication conflicts, which may be involved in R-loop unwinding.
Transient characteristics of a GdBCO racetrack pancake coil without turn-to-turn insulation

This paper reports the transient characteristics of two types of magnetically coupled GdBCO racetrack pancake coils: (1) a pair of insulated coils (INS–INS coils) and (2) a pair of non-insulated coils (NI–NI coils). In order to investigate the electromagnetic behavior of the INS–INS and NI–NI coils, charging/sudden discharging tests were performed with respect to the distance between primary and secondary coils of the coil pairs. The charging/sudden discharging test results show that the amount of induced current and measured axial magnetic field decreased with increasing distance between the primary and secondary coils. Additionally, charge and discharge delays were clearly observed in the NI–NI coils. The simulated results show good agreement with the experimental results, which validates the proposed approach involving an equivalent circuit model.
Local Stochastic Volatility with Jumps: Analytical Approximations

We present new approximation formulas for local stochastic volatility models, possibly including Levy jumps. Our main result is an expansion of the characteristic function, which is worked out in the Fourier space. Combined with standard Fourier methods, our result provides efficient and accurate formulas for the prices and the Greeks of plain vanilla options. We finally provide numerical results to illustrate the accuracy with real market data.
Measurements of X-Ray Selected AGN and Novel Superconducting X-Ray Detectors

Major astrophysical advances typically come through combining new observational approaches with new technologies. This thesis involves work on both fronts, combining observational work using data from the Chandra X-ray Observatory and Keck Observatory with novel superconducting detector development to further technology for future observatories. The subject of the first part of this thesis is the Serendipitous Extragalactic X-ray Source Identification (SEXSI) program, a survey using Chandra data selected to probe the dominant contributors to the 2-10 keV cosmic X-ray background. SEXSI covers more than 2 square degrees of sky and employs optical photometric and spectroscopic followup of sources discovered in archival Chandra fields. The resulting sample consists of 1034 hard X-ray-selected sources with R-band optical-followup imaging, and optical spectroscopy for 477 of the sources, filling the gap between wide-area, shallow surveys and the deep, pencil-beam surveys. The vast majority of the 2-10 keV-selected sample are AGN with redshifts between 0.1 and 3. We discuss results from our survey, including the spectroscopic properties of hard X-ray sources and the relationship between X-ray and optical properties of our sources. In addition, we present infrared data from the Spitzer Space Telescope that cover a subset of the Chandra fields, which allows us to explore the relative strengths of Chandra and Spitzer as black-hole finders. The second part of this thesis focuses on microwave kinetic inductance detectors (MKIDs), a superconducting detector technology that has breakthrough potential for providing megapixel imagers with several eV energy resolution for use in future X-ray missions. These detectors utilize simple, thin-film lithographed microwave resonators as photon detectors in a multiplexed readout approach. X-ray absorption in a superconductor creates quasiparticle excitations, with number proportional to the X-ray energy. The surface impedance of a superconductor changes with the quasiparticle density, and if operated at T MKIDs offer the advantage over many other cryogenic detector technologies that they can be easily multiplexed by coupling many resonators to a single microwave transmission line. In addition, the readout electronics can be operated at room temperature, a significant advantage for space applications. The practical application of MKIDs for photon detection requires a method of efficiently coupling the photon energy to the MKID. To this end we have been studying MKIDs in a strip detector architecture. The second part of this thesis presents our results using strip detectors with tantalum absorbers coupled to aluminum MKIDs.
Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury

Astrocytes and microglia play an orchestrated role following spinal cord injury; however, the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood. Herein, microglia were pharmacologically depleted and the effects on the astrocytic response were examined. We further explored the potential mechanisms involving the signal transducers and activators of transcription 3 (STAT3) pathway. For in vivo experiments, we constructed a contusion spinal cord injury model in C57BL/6 mice. To deplete microglia, all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397, starting 2 weeks prior to surgery until they were sacrificed. Cell proliferation was examined by 5-ethynyl-2-deoxyuridine (EdU) and three pivotal inflammatory cytokines were detected by a specific Bio-Plex ProTM Reagent Kit. Locomotor function, neuroinflammation, astrocyte activation and phosphorylated STAT3 (pSTAT3, a maker of activation of STAT3 signaling) levels were determined. For in vitro experiments, a microglia and astrocyte coculture system was established, and the small molecule STA21, which blocks STAT3 activation, was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia. PLX3397 administration disrupted glial scar formation, increased inflammatory spillover, induced diffuse tissue damage and impaired functional recovery after spinal cord injury. Microglial depletion markedly reduced EdU+ proliferating cells, especially proliferating astrocytes at 7 days after spinal cord injury. RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397. Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes. Importantly, in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration. These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation, and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.
A photo‐based communication intervention to promote diet‐related discussions among older adults with multi‐morbidity

Little is known about how to best communicate with older adults about dietary behaviors and related factors in complex chronic disease care. Photo‐based communication could promote efficient information exchange and activate patients to effectively communicate their lived experiences. We conducted a pilot study to assess the feasibility and acceptability of a photo‐based patient‐clinician communication intervention to promote dietary discussions in geriatric primary care.
Global features of Kelvin‐Helmholtz waves at the magnetopause for northward interplanetary magnetic field

We investigate the global features of Kelvin‐Helmholtz waves (KHW) at the low‐latitude magnetopause for constant northward interplanetary magnetic field conditions, using global magnetohydrodynamic simulations. The root‐integrated power (RIP) of X component of bulk velocity is employed to analyze the magnetopause mode of KHW along the boundary layer. The RIP distribution of the outer KHW is much broader than that of the inner one, and the maximum amplitude of global KHW occurs near the dawn/dusk terminator regions. In the dayside magnetopause, the phase of the waveform at middle latitudes leads to that at low latitudes, while the situation reversed in the nightside. The global evolution of KHW phases is a representation of an interesting feature that the axis of the Kelvin‐Helmholtz vortex aligns with the geomagnetic field lines. We suggest that the reported features may also exist in other KHW active regions with flow‐sheared plasma.
Scaling exponents of the second-order structure function of turbulence

The Kolmogorov equation, which is an exact relationship between the second-order structure function and the third-order structure function , is applied to study the relative scaling of against according to the extended self-similarity (ESS) method. It is found that the relative ESS scaling exponent is greater than the real (or theoretical) inertial range scaling exponent of in the case of normal scaling as well as anomalous scaling : when and when . Therefore, the experimental and numerical results favours the Kolmogorov 2/3 law rather than anomalous scaling . Previously the results were interpreted as clear evidence of anomalous scaling based upon the assumption that .
Inhibiting the biogenesis of myeloid-derived suppressor cells enhances immunotherapy efficacy against mammary tumor progression

While immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape in oncology, they are effective in select subsets of patients. Efficacy may be limited by tumor-driven immune suppression, of which 1 key mechanism is the development of myeloid-derived suppressor cells (MDSCs). A fundamental gap in MDSC therapeutics is the lack of approaches that target MDSC biogenesis. We hypothesized that targeting MDSC biogenesis would mitigate MDSC burden and bolster tumor responses to ICIs. We tested a class of agents, dihydroorotate dehydrogenase (DHODH) inhibitors, that have been previously shown to restore the terminal differentiation of leukemic myeloid progenitors. DHODH inhibitors have demonstrated preclinical safety and are under clinical study for hematologic malignancies. Using mouse models of mammary cancer that elicit robust MDSC responses, we demonstrated that the DHODH inhibitor brequinar (a) suppressed MDSC production from early-stage myeloid progenitors, which was accompanied by enhanced myeloid maturation; (b) augmented the antitumor and antimetastatic activities of programmed cell death 1–based (PD-1–based) ICI therapy in ICI-resistant mammary cancer models; and (c) acted in concert with PD-1 blockade through modulation of MDSC and CD8+ T cell responses. Moreover, brequinar facilitated myeloid maturation and inhibited immune-suppressive features in human bone marrow culture systems. These findings advance the concept of MDSC differentiation therapy in immuno-oncology.
Analytical Well Models for Reservoir Simulation

The computation of flowing well bottom-hole pressure from the pressure of the block containing the well, or the computation of well flow rate when the flowing bottom-hole well pressure is specified, are important considerations in reservoir simulation. While this problem has been addressed by several authors, some important aspects of the problem ae not adequately treated in the literature. An analytical method is presented for computing the well block factors (constants of the productivity index) for a well coated anywhere in a square or rectangular block. Equations for well geometric factors and well fraction constants are given for grid blocks of various types, containing a single well, encountered in reservoir simulation studies. The equations given can be used for both block-centered and point-distributed grids in 5- and 9-point (2-dimensional) finite difference formulations. However, the radial flow assumption utilized in deriving the equations is not always strictly valid. For most practical situations it provides an adequate approximation for near well flow. 12 ref. ).
Bioluminescence Goes Dark: Boosting the Performance of Bioluminescent Sensor Proteins Using Complementation Inhibitors

Bioluminescent sensor proteins have recently gained popularity in both basic research and point-of-care diagnostics. Sensor proteins based on intramolecular complementation of split NanoLuc are particularly attractive because their intrinsic modular design enables for systematic tuning of sensor properties. Here we show how the sensitivity of these sensors can be enhanced by the introduction of catalytically inactive variants of the small SmBiT subunit (DarkBiTs) as intramolecular inhibitors. Starting from previously developed bioluminescent antibody sensor proteins (LUMABS), we developed single component, biomolecular switches with a strongly reduced background signal for the detection of three clinically relevant antibodies, anti-HIV1-p17, cetuximab (CTX), and an RSV neutralizing antibody (101F). These new dark-LUMABS sensors showed 5–13-fold increases in sensitivity which translated into lower limits of detection. The use of DarkBiTs as competitive intramolecular inhibitor domains is not limited to the LUMABS sensor family and might be used to boost the performance of other bioluminescent sensor proteins based on split luciferase complementation.
Updated insight into the characterization of nano-emulsions

ABSTRACT Introduction In most of the studies, nano-emulsion characterization is limited to their size distribution and zeta potential. In this review, we present an updated insight of the characterization methods of nano-emulsions, including new or unconventional experimental approaches to explore in depth the nano-emulsion properties. Area covered We propose an overview of all the main techniques used to characterize nano-emulsions, including the most classical ones, up to in vitro, ex vivo and in vivo evaluation. Innovative approaches are then presented in the second part of the review that presents innovative, experimental techniques less known in the field of nano-emulsion such as the nanoparticle tracking analysis, small-angle X-ray scattering, Raman spectroscopy, and nuclear magnetic resonance. Finally, in the last part we discuss the use of lipophilic fluorescent probes and imaging techniques as an emerging tool to understand the nano-emulsion droplet stability, surface decoration, release mechanisms, and in vivo fate. Expert opinion This review is mostly intended for a broad readership and provides key tools regarding the choice of the approach to characterize nano-emulsions. Innovative and uncommon methods will be precious to disclose the information potentially reachable behind a formulation of nano-emulsions, not always known in first intention and with conventional methods.
Preliminary Comparison of the Conventional and Quasi‐Snowflake Divertor Configurations with the 2D Code EDGE2D/EIRENE in the FAST Tokamak

The new magnetic configurations for tokamak divertors, snowflake and super‐X, proposed to mitigate the problem of the power exhaust in reactors have clearly evidenced the need for an accurate and reliable modeling of the physics governing the interaction with the plates. The initial effort undertaken jointly by ENEA and IPPLM has been focused to exploit a simple and versatile modeling tool, namely the 2D TECXY code, to obtain preliminary comparison between the conventional and snowflake configurations for the proposed new device FAST that should realize an edge plasma with properties quite close to those of a reactor. The very interesting features found for the snowflake, namely a power load mitigation much larger than expected directly from the change of the magnetic topology, has further pushed us to check these results with the more sophisticated computational tool EDGE2D coupled with the neutral code module EIRENE. After a preparatory work that has been carried out in order to adapt this code combination to deal with non‐conventional, single null equilibria and in particular with second order nulls in the poloidal field generated in the snowflake configuration, in this paper we describe the first activity to compare these codes and discuss the first results obtained for FAST. The outcome of these EDGE2D runs is in qualitative agreement with those of TECXY, confirming the potential benefit obtainable from a snowflake configuration. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)