Miracle-dz/UniFAR-FTUs huggingface dataset:
Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates

Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch’s effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4β7 in conventional T cells while preserving α4β7 in regulatory T cells, with findings suggesting increased β1 competition for α4 binding in conventional T cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4β7 integrin in T cells after allo-HCT. Together, DLL4-Notch blockade decreased effector T cell infiltration into the gut, with increased regulatory to conventional T cell ratios early after allo-HCT. Our results identify a conserved, biologically unique, and targetable role of DLL4-Notch signaling in intestinal GVHD. Description Evolutionarily conserved Notch signaling promotes pathogenic effector T cell infiltration of the intestine during acute graft-versus-host disease. Editor’s summary Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation, and additional treatment strategies are urgently needed. Here, Tkachev et al. moved one candidate treatment, blockade of the Delta-like Notch ligand DLL4, closer to the clinic. DLL4 blockade has previously been shown to control aGVHD in mice, and here the authors found that that efficacy translated into nonhuman primate models. The authors also identified the mechanism by which the treatment may specifically control intestinal aGVHD; DLL4 blockade decreased effector T cell infiltration into the gut, thereby increasing the relative frequency of regulatory T cells. These studies highlight the clinical potential for targeting DLL4-Notch signaling for patients with aGVHD. —Courtney Malo
Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice

Inner ear gene therapy has recently effectively restored hearing in neonatal mice, but it is complicated in adulthood by the structural inaccessibility of the cochlea, which is embedded within the temporal bone. Alternative delivery routes may advance auditory research and also prove useful when translated to humans with progressive genetic-mediated hearing loss. Cerebrospinal fluid flow via the glymphatic system is emerging as a new approach for brain-wide drug delivery in rodents as well as humans. The cerebrospinal fluid and the fluid of the inner ear are connected via a bony channel called the cochlear aqueduct, but previous studies have not explored the possibility of delivering gene therapy via the cerebrospinal fluid to restore hearing in adult deaf mice. Here, we showed that the cochlear aqueduct in mice exhibits lymphatic-like characteristics. In vivo time-lapse magnetic resonance imaging, computed tomography, and optical fluorescence microscopy showed that large-particle tracers injected into the cerebrospinal fluid reached the inner ear by dispersive transport via the cochlear aqueduct in adult mice. A single intracisternal injection of adeno-associated virus carrying solute carrier family 17, member 8 (Slc17A8), which encodes vesicular glutamate transporter-3 (VGLUT3), rescued hearing in adult deaf Slc17A8−/− mice by restoring VGLUT3 protein expression in inner hair cells, with minimal ectopic expression in the brain and none in the liver. Our findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step toward using gene therapy to restore hearing in humans. Description Hearing in adult deaf mice can be rescued by delivering gene therapeutics to the cochlea from the cisterna magna via the cochlear aqueduct. Editor’s summary Although gene therapy can treat genetic hearing loss in neonatal mice, treating adult animals is harder because of the location of the cochleae and the risk of damage to inner ear structures. Here, Mathiesen and colleagues showed that the cochlear aqueduct connects the cerebrospinal fluid (CSF) and cochlear fluid in adult mice. Tracers injected into the CSF reached the mouse inner ear, and intracisternal injection of an adeno-associated virus carrying the solute carrier family 17, member 8 (Slc17A8) gene restored vesicular glutamate transporter-3 protein in the inner hair cells of the cochlea and rescued hearing in Slc17A8 knockout mice. These findings suggest that CSF administration of gene therapy through the cochlear aqueducts could be a treatment for genetic deafness in adults. —Melissa Norton
A coherent composite approach for the continuous circular hydraulic jump and vortex structure

Abstract We examine the structure of the continuous circular hydraulic jump and recirculation for a jet impinging on a disk. We use a composite mean-field thin-film approach consisting of subdividing the flow domain into three regions of increasing gravity strength: a developing boundary layer near impact, an intermediate supercritical viscous layer and a region comprising the jump and subcritical flow. Unlike existing models, the approach does not require any empirically or numerically adjusted boundary conditions. We demonstrate that the stress or corner singularity for a film draining at the edge is equivalent to an infinite slope of the film surface, which we impose as the downstream boundary condition. The model is validated against existing experiment and numerical simulation of the boundary-layer and Navier–Stokes equations. We find that the flow in the supercritical region remains insensitive to the change in gravity level but is greatly affected by viscosity. The existence of the jump is not necessarily commensurate with the presence of recirculation, which is strongly dependent on the upstream curvature and steepness of the jump.
Particle orbiting constrained by elastic filament as a model cilium for fluid pumping

Abstract Many microorganisms use cilia to propel themselves in low Reynolds number ($Re$) environments. In this work, we study the dynamics of a composite cilium consisting of an elastic filament and a spherical particle attached at the filament tip driven by an external time-periodic force acting on the particle. The elastic filament is modelled numerically using a slender body theory with hydrodynamic interactions. When tilted at a large angle from the normal direction of the wall, the filament buckles, and the induced velocity field by the cilium shows a large net flux. By varying the tilt angle or the force amplitude, the particle trajectory and the net flux display abrupt changes along with a reversal of the buckling direction. We further demonstrate through a segmental model that the abrupt changes arise from the deviation of the cilium orientation at the start of the recovery stroke from the natural orientation. Our results suggest a simple approach to engineering particle motions and designing artificial cilia for fluid pumping in low $Re$ environments.
An experimental study of off-centred rotating thermal convection: a laboratory model for the tidal effects

Abstract A novel experiment was performed in rotating Rayleigh–Bénard convection (RRBC), wherein the convection cell with radius $R$ was shifted away from the rotation axis by a distance $d$. In this case, the centrifugal force felt by a fluid parcel (characterized by the Froude number $Fr$) can be decomposed into an axisymmetrical part $Fr_R$ and a directed one $Fr_d$. It has been reported that the global heat transport enhances at $Fr_{d,c}$ and then reaches an optimal state at $Fr_{d,max}$ (Hu et al., Phys. Rev. Lett., vol. 127, 2021, 244501). In this paper, the local properties after the offset effects set in are investigated further, which show different features before and after $Fr_{d,max}$. The local temperature measurements at the cell centre reveal that the bulk flow turns from a turbulent state into a laminar state at $Fr_{d,max}$, which is consistent with the particle image velocimetry results. This transition can be qualitatively understood by an equivalent tilted RRBC system. As for the hot and cold coherent structures near the sidewall, their vertical temperature variations reach a minimum at $Fr_{d,max}$, implying that these structures are mostly uniform in the vertical direction at $Fr_{d,max}$. Their temperature contrasts show a linear dependence on $Fr_d$ and start to deviate from this linear behaviour when $Fr_d>Fr_{d,max}$. Besides the dominant effects of $Fr_d$, the secondary effects of $Fr_R$ are also investigated. Due to the positive effect of $+Fr_R$ on the cold structure and the negative effect of $-Fr_R$ on the hot one, the cold structure is more coherent than the hot one, but its size is smaller. The shift of the cold cluster centre from the farthest point is also larger than the shift of the hot one from the nearest point.
Systematic Revision of the Whip Spider Family Paracharontidae (Arachnida: Amblypygi) with Description of a New Troglobitic Genus and Species from Colombia

ABSTRACT The ancient, enigmatic whip spider family Paracharontidae Weygoldt, 1996, representing the basalmost lineage of the arachnid order Amblypygi Thorell, 1883, is revised. The monotypic West African genus Paracharon Hansen, 1921, from Guinea Bissau, is redescribed, based on a reexamination and reinterpretation of the newly designated lectotype. A new troglobitic whip spider, Jorottui ipuanai, gen. et sp. nov., is described from a cave system in the upper basin of the Camarones River in the La Guajira Department of northeastern Colombia. This new taxon is the second extant representative of Paracharontidae and the first outside Africa. It is unambiguously assigned to the family based on several characters shared with Paracharon caecus Hansen, 1921, notably a projection of the anterior carapace margin, the tritosternum not projecting anteriorly, similar pedipalp spination, a reduced number of trichobothria on the tibia of leg IV, and cushionlike female gonopods. A detailed examination confirmed the absence of ocelli in both genera and the presence of three (Paracharon) vs. four (Jorottui, gen. nov.) prolateral teeth on the basal segment of the chelicera, the dorsalmost tooth bicuspid in both genera. The male gonopods of Paracharontidae are described for the first time. Paracharonopsis cambayensis Engel and Grimaldi, 2014, is removed from Paracharontidae and placed incertae sedis in Euamblypygi Weygoldt, 1996; amended, comparative diagnoses are presented for Paracharontidae and Paracharon; and previous interpretations of various diagnostic characters for Paracharontidae are discussed.
The Impact of Free-Play: A Longitudinal Study of Trip-Level Visitation and Wagering Behavior

The aim of this study was to understand the impacts of changes in free-play (FP) award values on visitation frequency and gaming revenue. With costly and perpetual FP campaigns well established in many markets, a critical issue for operators centers on the potential consequences of walking back offer values, especially when nearby competitors do not. The results of experimentally manipulated FP offers suggested that widely held industry beliefs about their ability to influence visitation are equivocal. Additional outcomes related to the economic impact of FP awards across the experimental groups also questioned the sensitivity of loyalty club members to reductions in FP offers. Working from a common offer tier of 600 loyalty club members, subjects were randomly assigned to one of six groups, each comprised of 100 subjects. Daily group-level outcomes were produced by aggregating player performance data over a 191-day sample period, collected from the records of a tribal casino operating in a competitive repeater market. This longitudinal design allowed for the measurement of multiple levels of FP offers on visitation behavior and gaming value, over a meaningful duration. Our findings fill gaps in the literature related to the impacts of FP on visitation frequency and the ability to drive own-money wagering. Our results also add to literature within the domains of operant conditioning, goal gradient theory, and a growing stream of research on FP efficacy. There are also connections to the house money effect, reverse house money effect, and the endowment effect.
Clinical and therapeutic features of myositis associated with anti-MDA5 antibodies: three new cases

Abstract Purpose To assess clinical features, therapy, and outcome of the myositis associated with anti-MDA5 antibodies, and to propose a successful therapeutic protocol for rapidly progressive interstitial lung disease (RP-ILD) in anti-MDA5 dermatomyositis (DM). Methods A retrospective and descriptive study of three cases of anti-MDA5 associated myositis was conducted in the Department of Internal Medicine in the University Hospital Hedi Chaker, Sfax, Tunisia, between 1996 and 2016. Results From a series of 115 cases of myositis, three cases of anti-MDA5-positive DM were identified. They were three men with a mean age of 63 years. They manifested specific cutaneous manifestations including ulcers and palmar papules, mild muscular involvement, and RP-ILD. The severity of the disease was correlated to the ILD in all patients. Aggressive therapies were tried including high-dose corticoids, cyclophosphamide (CYC) cures, intravenous immunoglobulins, and rituximab (RTX), with a good outcome in the patient who received combined high steroids, CYC, and RTX pulses. The two other patients died because of a rapid worsening of their respiratory condition. Conclusion Anti-MDA positive myositis is characterised by a specific cutaneous phenotype, the discretion of muscular signs, and the correlation with RP-ILD. The poor prognosis of this entity is correlated to the high resistance of pulmonary involvement despite aggressive therapeutics. The combination between high-dose steroids, CYC, and RTX has shown good results in many reports, as well as in one of our patients.
Digital marketing adoption of microenterprises in a technology acceptance approach

Abstract External knowledge sources such as professional social media accounts represent an understudied domain in the digital media adoption literature of small enterprises. This article extends the Technology Acceptance Model with two additional factors – external knowledge source and trust in digital marketing professionals – to better understand the digital marketing adoption of microenterprises. We collected and analyzed data from 181 microenterprises using online survey and structural equation modeling methodology. Results indicate that participation in events and following professional Facebook groups are positively related to perceived ease of use, while following professional Facebook groups, blogs, and vlogs, and meeting consultants are positively related to perceived usefulness. Besides, trust in marketing professionals has a significant effect on both perceived ease of use and perceived usefulness. By applying the technology-in-practice literature to digital marketing adoption, the article highlights that marketing professionals can be a bridge between academia and small business managers by contextualizing and translating formal knowledge to practical easy-to-understand knowledge.
Bankruptcy Prediction Model Development and its Implications on Financial Performance in Slovakia

Abstract Research purpose. Financial distress being a global phenomenon makes it impact firms in all sectors of the economy and predicting corporate bankruptcy has become a crucial issue in economics. At the beginning of the last century, the first studies aimed to predict corporate bankruptcy were published. In Slovakia, however, several prediction models were developed with a significant delay. The main aim of this paper is to develop a model for predicting bankruptcy based on the financial information of 3,783 Slovak enterprises operating in the manufacturing and construction sectors in 2020 and 2021. Design / Methodology / Approach. A prediction model that uses the appropriate financial indicators as predictors may be developed using multiple discriminant analysis. Multiple discriminant analysis is currently used in prediction model development. In this case, financial health is assessed using several variables that are weighted in order to maximise the difference between the average value calculated in the group of prosperous and non-prosperous firms. When developing a bankruptcy prediction model based on multiple discriminant analysis, it is crucial to determine the independent variables used as primary financial health predictors. Findings. Due to the discriminant analysis results, the corporate debt level of the monitored firms may be regarded as appropriate. Despite the fact that the model identified 215 firms in financial distress due to an insufficient debt level, 3,568 out of 3,783 Slovak enterprises operating in the manufacturing and construction sectors did not have any problems with financing their debts. The self-financing ratio was identified in the developed model as the variable with the highest accuracy. Based on the results, the developed model has an overall discriminant ability of 93% since bankruptcy prediction models require strong discriminating abilities to be used in practice. Originality / Value / Practical implications. The principal contribution of the paper is its application of the latest available data, which could help in more accurate financial stability predictions for firms during the current difficult period. Additionally, this is a ground-breaking research study in Slovakia that models the financial health of enterprises in the post-pandemic period.
Insights into the bubble formation dynamics in converging shape microchannels using CLSVOF method

Abstract Bubble formation in a square microchannel having a converging shape merging junction has been studied using the Coupled Level-Set and Volume-of-Fluid (CLSVOF) method. The influence of variations in merging junction angles, fluid properties, and operating conditions on the bubble length and pressure drop has been analyzed. The results show a direct relationship between surface tension, gas-liquid flow ratio, and the inverse relation of continuous phase viscosity with the bubble length. Moreover, opposite variations of these parameters are observed for pressure drop. This work reveals a discerning influence of the angle variations of merging junction on the interplay between inertial, viscous, and surface tension forces in the bubble formation mechanism. We envisage that this numerical work will be of significant interest for the process intensification in various industries that deal with gas-liquid microfluidic systems.
Owfuzz: Discovering Wi-Fi Flaws in Modern Devices through Over-The-Air Fuzzing

Fuzzing is a practical approach to discovering flaws in the design and implementation of Wi-Fi protocols. However, existing Wi-Fi fuzzers are either vendor- or ecosystem-specific. Besides, they only cover a subset of 802.11 protocols and frame types. The growing complexity of Wi-Fi protocols, which have evolved to Wi-Fi6 and WPA3 already, calls for a free and comprehensive fuzzing tool for modern Wi-Fi devices. In this paper, we present such a fuzzing tool named Owfuzz. Unlike previous works using mostly firmware emulation fuzzing or driver fuzzing, Owfuzz takes the over-the-air fuzzing approach. It can perform fuzzing tests on arbitrary Wi-Fi devices from any vendor and can fuzz all three types of Wi-Fi frames (management, control, and data) defined in all versions of the 802.11 standards. It can be easily extended to support interactive testing of various protocol models. With Owfuzz, we have tested the products of mainstream Wi-Fi chip and device vendors, leading to the discovery of 23 flaws. We have reported most of these flaws to the related vendors with 8 CVE IDs assigned. Moreover, we have open-sourced Owfuzz to the community to facilitate future research.
A non-probabilistic model of structural reliability based on interval analysis

In this paper,the uncertain parameters of structures are expressed by non\|probabilistic interval variables. Based on interval arithmetic, a non\|probabilistic measure and analysis methodology for structural reliability computpation is presented. The measure index of the non\|probabilistic reliability developed here has a clear meaning in physics and geometry. The rationality and feasibility of the proposed theory is explained. Examples of practical application are given.
Survey on Sketch-to-photo Translation

Sketch-based understanding is involved in human communication and cognitive development, making it essential in visual perception. A specific task in this domain is sketch-to-photo translation, where a model produces realistic images from simple drawings. To this end, large paired training datasets are commonly required, which is impractical in real applications. Thus, this work studies conditional generative models for sketch-to-photo translation, overcoming the lack of training datasets by a self-supervised approach that produces sketch-photo pairs from a target catalog. Our study shows the benefit of cycle-consistency loss and UNet architectures that, together with the proposed dataset generation, improve performance in real applications like eCommerce. Our results also reveal the weakness of conditional DDPMs for generating images resembling the input sketch, even though they achieve a high FID score.
The Devil is in the Details: Hidden Problems of Client-Side Enterprise Wi-Fi Configurators

In the context of connecting to enterprise Wi-Fi, previous works show that relying on human users to manually configure or enforce server authentication often leads to insecure outcomes. Consequently, many user credentials can potentially be stolen by the so-called "Evil-Twin'' (ET) attack. To ease the burden of human users, various easy-to-use Wi-Fi configurators have been released and deployed. In this work, we investigate whether such configurators can indeed protect users from variants of the ET attack. To our surprise, the results of our investigation show that all configurators considered in the study suffer from certain weaknesses due to their design, implementation, or deployment practices. Notable findings include a series of design flaws in the new trust-on-first-use (TOFU) configurator on Android (available since version 12), which can be exploited in tandem to achieve a stealthy ET attack. Moreover, we found that 2 open-source Android Wi-Fi configurators fail to properly enforce server authentication under specific situations. The cause of these could be partly attributed to the complexity stemmed from certificate name matching as well as the limitations of the Android API. Last but not least, we found that a commercial configurator not only allows insecure Wi-Fi configurations to be deployed, but also the covert injection of certificates on the user device to facilitate interception of other TLS traffic, posing yet another hidden security and privacy threat to its users. All in all, this study shows that despite years of research on the topic, developing a user-friendly yet reliable Wi-Fi configurator remains an elusive goal, and thus the threat of ET attacks continues to be relevant. As such, it is time to rethink whether the complexity of the standard certificate chain validation is actually good for enterprise Wi-Fi.