Miracle-dz/UniFAR-FTUs huggingface dataset:
Flat free boundaries regularity in two-phase problems for a class of fully nonlinear elliptic operators with variable coefﬁcients

In this paper we prove that flat free boundaries of the solutions of elliptic two-phase problems associated with a class of fully nonlinear operators are C1,γ . In [11] the C1,γ regularity of Lipschitz free boundaries of two-phase problems was proved for a class of homogeneous fully nonlinear elliptic operators F(D2u(x), x), containing convex (concave) operators, with Holder dependence on x. Here we consider the same class of operators. More precisely, we prove the regularity of flat free boundaries of the solutions of the following two-phase problems:  F(D2u(x), x) = 0 in Ω(u) = {x ∈ Ω ⊂ R : u > 0}, F (D2u(x), x) = 0 in Ω(u) = {x ∈ Ω ⊂ R : u 6 0}, u = 0 on Fu, u+ν = G(u − ν ) on Fu, (1)
Jammer Localization in the Internet of Vehicles: Scenarios, Experiments, and Evaluation

The Internet of Vehicles (IoV) paradigm aims to improve road safety and provide a comfortable driving experience for Internet-connected vehicles, by transmitting early warning and infotainment signals to Internet-connected vehicles in the network. The unique characteristics of the IoV, such as their mobility and pervasive Internet connectivity, expose such networks to many cyberattacks. In particular, jamming attacks represent a considerable risk to their performance, as they can significantly affect vehicles’ functionality, possibly leading to collisions in dense networks. This paper presents a new scheme enabling the detection and localization of jamming attacks carried out within an IoV network. We consider several scenarios, e.g., where the Internet-connected vehicles and the jammer are statically positioned, as when parked on a street, moving in the same direction and with variable speeds, and moving in opposite directions. We leverage the physical-layer characteristics of the received signals, particularly the Received Signal Strength (RSS), and devise a solution minimizing the jammer localization error based on a set of antennas deployed on the vehicle. Specifically, we compute the power emitted by the jammer and received by the arrays of omnidirectional antennas and we use such values to estimate the location of the jammer in the previous-cited scenarios. Through an extensive simulation campaign, we provide a thorough study of our algorithm, evaluating the effect of several system and channel parameters on the measurement error. The results obtained for all scenarios show a significant localization accuracy, i.e., ranging from 0.23 meters to 13 meters, depending on the channel conditions.
The journey of gene therapy in haemophilia – putting the patient at the centre of the hub and spoke model

Abstract As gene therapy for haemophilia is now licensed in Europe, and the hub and spoke approach is widely promoted for its delivery and follow-up, it is essential that people with haemophilia (PwH) who are eligible and opt to have this treatment are enabled to obtain the maximum benefit. Ensuring the pathway that makes up the patient gene therapy journey is effective is key to achieving this. EAHAD and the EHC have recommended that gene therapy is delivered through a hub and spoke model of care to ensure that the right expertise is available throughout the various stages of the haemophilia gene therapy journey. Effective communication between hub and spoke centres is essential, and the processes that make up the journey must be understood clearly by both PwH and the multidisciplinary teams delivering their care. The starting point for this is to take each step of the gene therapy journey in turn – through initial engagement, eligibility, detailed patient education, informed decision-making, dosing, and follow up in year 1, year 2 and beyond – and to consider and identify the roles and responsibilities of the patient, the hub centre and the spoke centre. It is important that the expectations of both health care practitioners (HCPs) and patients are aligned with the key challenges and goals associated with each step. Understanding these from the patient point of view will help to ensure that the individual PwH treading this path receive the information, guidance and support they need from hub and spoke HCPs throughout their journey, and that they, as the patient, remain the focus of care. Visualising the journey may help to explain the gene therapy clinical pathway to PwH and could provide a useful tool for HCPs in spoke centres. Visualisation may also serve as a tool for facilitating discussion, not only in terms of initial engagement and education, but throughout the haemophilia gene therapy journey.
Patient-reported outcomes using a wearable cardioverter-defibrillator: results from a systematic review

Abstract Objectives The aim of this study was to assess the effect of the wearable cardioverter-defibrillator (WCD) on patient-reported outcomes (PRO) in adult patients with high risk for sudden cardiac arrest. Methods We performed a systematic literature search in Medline (via PubMed) and Cochrane Library in February 2022 and included studies with a study population ≥18 years and prescribed WCD. PRO include health-related quality of life (QoL), symptoms, utilities, or satisfaction ratings. Study selection was done by two reviewers independently using predefined inclusion and exclusion criteria. Quality assessment of studies as well as data extraction was performed by one author and approved by a second author. Results of the included studies are presented quantitatively. Results One randomized controlled trial (RCT), one comparative non-randomized trial, and three single-arm trials were included. QoL was assessed in four studies, but with different assessment tools. One study additionally evaluated the change in depressive symptoms and anxiety and one study focused on acceptability of WCD but evaluated items that are closely related to QoL. Results of the RCT show no statistically significant difference in QoL assessed by SF-36 and EQ-5D comparing WCD and Guideline-Directed Medical Therapy (GDMT) versus GDMT alone. One comparative study reports an improvement in depressive symptoms and anxiety within groups but no significant difference between groups. Further, one single-arm study reported improvement in QoL between baseline and day 90 and day 180. Conclusions The available evidence demonstrates that the usage of WCD is not affecting PRO, like QoL, depressive symptoms or anxiety negatively.
The association of parathyroid hormone with serum 25-hydroxyvitamin during pregnancy

Abstract It is currently debated whether vitamin D requirements during pregnancy differ from those during non-gravid states. In current analyses, we aimed to determine the best model for the association between PTH and serum 25-hydroxyvitamin D (25(OH)D) and the threshold for circulating 25(OH)D at which serum parathyroid hormone (PTH) is suppressed. This multicenter prospective cross-sectional study was conducted on 227 Iranian pregnant women aged 15–45 years in their third trimester of pregnancy. The locally weighted smoothing scatter plot (LOWESS) was used to determine the curvilinear shape of the 25(OH)D/PTH relationship. Linear and non-linear methods were employed to determine the best fit and cut-point for serum 25(OH)D concentration. The median serum 25(OH)D and corresponding serum PTH concentration were 17⋅26 (13⋅44–23⋅08) ng/ml and 19⋅46 (15⋅08–25⋅04) pg/ml in our study population, respectively. The LOWESS curve suggested a non-linear and monotonic with a negative slope relation between PTH (pg/ml) and serum 25(OH)D (ng/ml). The optimal model for the association between PTH and serum 25(OH)D was a one-term fractional polynomial (FP1) (AIC = 1640⋅463). The FP1 analysis identified the 25(OH)D threshold of 12⋅48 ng/ml at which serum PTH rapidly rose. The expected degree of PTH stimulation seems to have a linear trend as 25(OH)D falls below 40 ng/ml. 25(OH)D (ng/ml) and PTH (pg/ml) had a non-linear and monotonic relationship with a negative slope. Our data suggest that a 25(OH)D threshold of 12⋅48 ng/ml is sufficient for parathyroid hormone suppression, which could be used to screen for deficient individuals.
Defects in liquid crystals

Defects are local breakings of symmetry in an ordered medium. The physics of defects has long been reduced to the study of dislocations in solids, and to the main physical phenomena they are responsible for, like plastic deformation. Dislocations break translational symmetries. Disclinations break rotational symmetries and are the basic defects of media with continuous symmetries, like liquid crystals. In this review, it is stressed how their study has contributed to a renewal of the physics of defects. Static and dynamic properties in the nematic, cholesteric, blue, smectic and columnar phases of liquid crystals are described in detail, up to the most recent results, for small-molecule thermotropic liquid crystals as well as for lyotropic and polymeric liquid crystals. The authors also discuss the homotopy classification of defects, including point defects, and compare it with the Volterra classification; finally they present the curved-crystal description of frustration in the light of the relevant situation in liquid crystals. The usefulness of the concepts introduced for liquid crystals for the study of other systems (structural problems in biology, dissipative structures, magnetic domains, etc.) is also emphasised.
The study of fibrotic scar at the long term spinal cord lesion rats

The fibrotic lesion formation is the main deterrent at regeneration of neurons in CNS injuries. In this paper we studied fibrotic scar formation in rat corticospinal tract lesion after one year survival time. The glial scar formation and Extracellular Matrix (ECM) fibronection derived scaffolds were investigated and the fore paw reaching task was performed during this period to see whether there is any regeneration of neurons along the lesion or not.
The statistics of natural shapes predict high-level aftereffects in human vision

Shape perception is essential for numerous everyday behaviors from object recognition to grasping and handling objects. Yet how the brain encodes shape remains poorly understood. Here, we probed shape representations using visual aftereffects—perceptual distortions that occur following extended exposure to a stimulus—to resolve a long-standing debate about shape encoding. We implemented contrasting low-level and high-level computational models of neural adaptation, which made precise and distinct predictions about the illusory shape distortions the observers experience following adaptation. Directly pitting the predictions of the two models against one another revealed that the perceptual distortions are driven by high-level shape attributes derived from the statistics of natural shapes. Our findings suggest that the diverse shape attributes thought to underlie shape encoding (e.g., curvature distributions, ‘skeletons’, aspect ratio) are the result of a visual system that learns to encode natural shape geometries based on observing many objects.
In Vivo Delivery of Therapeutic Molecules by Transplantation of Genome-Edited Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (iPSCs) have already been used in transplantation therapies. Currently, cells from healthy people are transplanted into patients with diseases. With the rapid evolution of genome editing technology, genetic modification could be applied to enhance the therapeutic effects of iPSCs, such as the introduction of secreted molecules to make the cells a drug delivery system. Here, we addressed this possibility by utilizing a Fabry disease mouse model, as a proof of concept. Fabry disease is caused by the lack of α-Galactosidase A (GLA). We previously developed an immunotolerant therapeutic molecule, modified α-N-acetylgalactosaminidase (mNAGA). We confirmed that secreted mNAGA from genome-edited iPSCs compensated for the GLA activity in GLA-deficient cells using an in vitro co-culture system. Moreover, iPSCs transplanted into Fabry model mice secreted mNAGA and supplied GLA activity to the liver. This study demonstrates the great potential of genome-edited iPSCs secreting therapeutic molecules.
Crosstalk between chromatin and the transcription factor Shavenbaby defines transcriptional output along the Drosophila intestinal stem cell lineage

The transcription factor Shavenbaby (Svb), the only member of the OvoL family in Drosophila, controls intestinal stem cell differentiation. Post-translational modification of Svb produces two protein isoforms, Svb-ACT and Svb-REP, which promote intestinal stem cell renewal or differentiation, respectively. Using engineered cell lines, we express either isoform to define their mode of action, and develop an unbiased method to identify Svb target genes in intestinal cells. Within a given cell type, Svb-ACT and Svb-REP antagonistically regulate the expression of a set of target genes, binding specific enhancers whose accessibility is constrained by. During intestinal differentiation, the set of target genes progressively changes, together with chromatin accessibility. Moreover, Svb-REP binding stabilizes three-dimensional enhancer-promoter loops, while influencing the local chromatin landscape to repress target genes. We propose that SvbACT-to-REP switch promotes enterocyte differentiation of intestinal stem cells through direct gene regulation and chromatin remodeling.
Tool-sensed object information effectively supports vision for multisensory grasping

Tools enable humans to extend their sensing abilities beyond the natural limits of their hands, allowing them to sense objects as if they were using their hands directly. The similarities between tool-mediated and hand-based sensing entail the existence of comparable processes for integrating tool- and hand-sensed information with vision, raising the intriguing question of whether tools can support vision in bimanual object manipulations. Here we investigated this question by measuring participants’ performance while reaching for and grasping objects either held with a tool or with their hand. We found that tool-mediated sensing effectively supports vision in multisensory grasping. Even more intriguingly, tool-mediated sensing resembled hand-based sensing. In addition, by manipulating the object features (availability of position and size versus position only), we found that both tool- and hand-mediated action performance was not hindered by the absence of size information. Thus, integrating the tool-sensed position of the object with its vision is sufficient to promote a multisensory advantage in grasping. In sum, our findings indicate that multisensory integration mechanisms significantly improve grasping actions, fine-tuning contralateral hand movements even when object information is only indirectly sensed through the hand operating a tool. Significance statement Tools allow extending the hands sensing capabilities beyond their anatomical limits. Here we show that object information sensed through a tool can guide bimanual object manipulations as effectively as when directly sensed by the hand. Both tool and hand sensing provide relevant object positional information that are merged with vision to improve action performance. Our findings provide evidence about the interchangeable use of tools and hands for skilled actions and open new perspectives for prosthetic applications and rehabilitative plans.
A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development

The specialized cell-types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell-fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying novel, multipotent early epithelial progenitors that execute multi-lineage cues before specialising into late-stage ionocytes, goblet and basal cells. Combining in silico lineage inference, in situ hybridization and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors, chart cell- type emergence and fate progression into specialized cell-types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programmes across vertebrates. We uncover a continuous non-hierarchical model of MCE development alongside a significant data resource for understanding respiratory biology.
Electrostatic Discharge Effects on AlGaN/GaN High Electron Mobility Transistors on Sapphire Substrates

The effects of electrostatic discharge (ESD) on the variation of electrical characteristics of AlGaN/GaN high electron mobility transistors (HEMTs), such as on-current, leakage current of gate and transconductance (gm), have been investigated. The failure phenomena of HEMTs due to the ESD stress have also been studied. We have applied the ESD stress by transmission line pulsing (TLP) method, which is widely used in ESD stress experiments, and measured the electrical characteristics before and after applying ESD stress. The on-current after applying ESD stress was increased because the space between the drain and the gate was narrowed due to the migration of the metal caused by the high electric field and temperature under the ESD stress. The leakage current was decreased and gm was changed slightly. The failure points were located mainly in the middle and on each side of the gate. AlGaN/GaN HEMTs, in contrast with GaAs HEMTs, have been shown to easily fail due to the poor thermal characteristics of the sapphire substrate.
Beyond Euler's Method: Implicit Finite Differences in an Introductory ODE Course

Abstract A typical introductory course in ordinary differential equations (ODEs) exposes students to exact solution methods. However, many differential equations must be approximated with numerical methods. Textbooks commonly include explicit methods such as Euler's and Improved Euler's. Implicit methods are typically introduced in more advanced courses and texts aimed specifically at numerical analysis or partial differential equations. This article will present techniques and advantages of using implicit methods in an early ODE course.
Potential of imputation for cost-efficient genomic selection for resistance to Flavobacterium columnare in rainbow trout (Oncorhynchus mykiss)

Background Flavobacterium columnare is the pathogen agent of columnaris disease, a major emerging disease affecting rainbow trout aquaculture. Selective breeding using genomic selection has potential to achieve cumulative improvement of host resistance. However, genomic selection is expensive partly due to the cost of genotyping high numbers of animals using high-density SNP arrays. The objective of this study was to assess the efficiency of genomic selection for resistance to F. columnare using in silico low-density (LD) panels combined with imputation. After a natural outbreak of columnaris disease, 2,874 challenged fish and 469 fish from the parental generation (n=81 parents) were genotyped with 27,907 SNPs. The efficiency of genomic prediction using LD-panels was assessed for panels of 10 different densities, created in silico using two sampling methods, random and equally spaced. All LD-panels were also imputed to the full 28K HD-panel using the parental generation as the reference population, and genomic predictions were reevaluated. The potential of prioritizing SNPs showing association with resistance to F. columnare was also tested for the six lower densities. Results Similar results were obtained with random and equally spaced sampling of SNPs for accuracy of both imputation and genomic predictions. Using LD-panels of at least 3,000 makers or lower density panels (as low as 300 markers) combined with imputation resulted in comparable accuracy to the 28K HD-panel and 11% higher accuracy than pedigree-based predictions. Conclusions Compared to using the commercial HD-panel, LD-panels with imputation may provide a more affordable route to genomic prediction of breeding values, supporting wider adoption of genomic selection in aquaculture breeding programmes.
E-Računi: Razlogi za Uporabo in Uporabniška Prijaznost

Digitalisation is a hot topic among businesses, policy makers and end-consumers. It is about the integration of digital technologies into business and social processes as well as everyday life. In this paper, we focus in e-invoices as a corner stone of digitalisation in business. With as survey among Slovenian companies, we examine the main reasons for adoption of e-invoices and their usability. The main conclusions are that rules imposed by the state are the main reason for adoption of e-invoices and that there is no significant difference in usability between paper invoices and e-invoices
A Neighbourhood-based Location- and Time-aware Recommender System

We address the problem of location- and time-aware recommender systems where users with dynamically changing locations are interested in trending and volatile items. Unlike existing work, we do not assume a known static location of each user and derive user-locational preferences from their long-term history of implicit feedback. We propose a recommendation model that accounts for spatial, temporal, popularity and social influences, thereby assuming items tagged with a location, i.e. geotag, city or country. Key ingredients of our online method include: (1) deriving location preferences from the history, (2) learning relevant nearby locations, (3) accounting for recency and popularity jointly, and (4) combining location- and time-aware recommendations with collaborative filtering. Supported by realistic offline and online experiments on a large dataset collected from a popular newspaper, and public datasets, we find that the proposed recommender outperforms content-based and time-aware collaborative filtering approaches.
Deep Reinforcement Learning Compared to Human Performance in Playing Video Games

Through deep reinforcement learning, a computer can learn to play simple video games under the same conditions as human players — by watching the pixels on the screen and issuing the button-press type of actions. In this paper, we investigate how quickly a computer can reach and surpass human performance in a simple two-player video game, given no background knowledge of how to play the game. We implement a Deep Q-Learning (DQN) algorithm using Python and integrate it with the Atari 2600 emulator that runs the Pong game. We train the neural network for up to 3 million training steps and evaluate its performance after every 100.000 steps. As a reference, we measure the performance of 18 human players and take their average rating as the human-level baseline. We propose an evaluation metric that considers the obtained game points and the player’s endurance during the game. We find that the Deep Q-Learning algorithm can surpass beginner-level human players in playing the Pong game after about 4 hours of training.