Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a clot-adhesive coating to improve the performance of thrombectomy devices

Background The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures. Methods Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model. Results Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model. Conclusion Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients.
Plant spatial aggregation modulates the interplay between plant competition and pollinator attraction with contrasting outcomes of plant fitness

Ecosystem functions such as seed production are the result of a complex interplay between competitive plant-plant interactions and mutualistic pollinator-plant interactions. In this interplay, spatial plant aggregation could work in two different directions: it could increase intra- and interspecific competition, thus reducing seed production; but it could also attract pollinators increasing plant fitness. To shed light on how plant spatial arrangement modulates this balance, we conducted a field study in a Mediterranean annual grassland with three focal plant species with different phenology (Chamaemelum fuscatum (early phenology), Leontodon maroccanus (middle phenology) and Pulicaria paludosa (late phenology)) and a diverse guild of pollinators (flies, bees, beetles, and butterflies). All three species showed spatial aggregation of conspecific individuals. Additionally, we found that the two mechanisms were working simultaneously: crowded neighborhoods reduced individual seed production via plant-plant competition, but they also made individual plants more attractive for some pollinator guilds, increasing visitation rates and plant fitness. The balance between these two forces varied depending on the focal species and the spatial scale considered. Therefore, our results indicate that mutualistic interactions not always effectively compensate for competitive interactions in situations of spatial aggregation of flowering plants, at least in our study system. We highlight the importance of explicitly considering the spatial structure at different spatial scales of multitrophic interactions to better understand individual plant fitness and community dynamics.
Responses of carbapenemase-producing and non-producing carbapenem-resistant Pseudomonas aeruginosa strains to meropenem revealed by quantitative tandem mass spectrometry proteomics

Pseudomonas aeruginosa is an opportunistic pathogen with increasing incidence of multidrug-resistant strains, including resistance to last-resort antibiotics, such as carbapenems. Resistances are often due to complex interplays of naturally and acquired resistance mechanisms that are enhanced by its remarkably large regulatory network. This study describes the proteomic responses of two carbapenem-resistant P. aeruginosa strains of high-risk clones ST235 and ST395 to subminimal inhibitory concentrations (sub-MICs) of meropenem by identifying differentially expressed proteins and pathways. Strain CCUG 51971, carries a VIM-4 metallo-β-lactamase or ‘classical’ carbapenemase, and strain CCUG 70744 carries no known acquired carbapenem-resistance genes and exhibits ‘non-classical’ carbapenem-resistance. Each strain was cultivated with different sub-MICs of meropenem, and analyzed, using quantitative shotgun proteomics, based on tandem mass tag (TMT) isobaric labeling followed by nano-liquid chromatography tandem-mass spectrometry. Exposure of both strains to sub-MICs meropenem resulted in hundreds of differentially expressed proteins, including β-lactamases, proteins associated with transport, peptidoglycan metabolism, cell wall organization, and regulatory proteins. Strain CCUG 51971 showed up-regulation of intrinsic β-lactamases and VIM-4 carbapenemase, while CCUG 70744 exhibited a combination of up-regulated intrinsic β-lactamases, efflux pumps, penicillin-binding proteins and down-regulation of porins. All components of the H1 type VI secretion system were up-regulated in strain CCUG 51971. Enrichment analyses revealed multiple metabolic pathways affected in both strains. Sub-MICs of meropenem cause marked changes in the proteomes of carbapenem-resistant strains of P. aeruginosa exhibiting different resistance mechanisms, involving a wide range of proteins, many uncharacterized, which might play a role in the susceptibility of P. aeruginosa to meropenem.
Radiation content of conformally flat initial data

We study the radiation of energy and linear momentum emitted to infinity by the head-on collision of binary black holes, starting from rest at a finite initial separation, in the extreme mass ratio (particle) limit. For these configurations we identify the radiation that may be attributed to a choice of the initial three geometry. This identification suggests that for evolution of holes from initial proper separations ${L}_{0}g~7M,$ the radiated energy and momentum from head-on collisions will not be dominated by that choice. For non-head-on orbits, where the amount of radiation is orders of magnitude larger, computations may be even less sensitive to the choice of initial three geometry.
Large-scale mass distribution behind the Galactic plane

We map the 1200 km s(-1) smoothed mass-density distribution in the Galactic zone of avoidance (ZOA), within 6000 km s(-1) of the Local Group, using POTENT reconstruction from peculiar velocities of galaxies. The interpolation into the ZOA is based on the assumed gravitational nature of the velocity field implying a potential now. The main dynamical features at a distance r similar to 4000 km s(-1) are (a) the peak of the Great Attractor connecting Centaurus and Pave at l similar or equal to 330 degrees, (b) a moderate bridge connecting Perseus-Pisces and Cepheus at l = 140 degrees, and (c) an extension of a large void from the southern Galactic hemisphere into the ZOA near the direction of Puppis, l = 220 degrees-270 degrees. We find a strong correlation between the mass density and the IRAS and optical galaxy density at b = +/- 20 degrees, which indicates that the main dynamical features in the ZOA should also be seen in galaxy surveys throughout the Galactic plane. The gravitational acceleration at the Local Group, based on the mass distribution out to similar to 6000 km s(-1), is strongly affected by the mass distribution in the ZOA: its direction changes by 31 degrees when the \b\<20 degrees ZOA is included, bringing it to within 4 degrees +/- 19 degrees of the CMB dipole.
Body temperature rebounds on sea ice and is elevated by mercury contamination in a keystone predator

Despite overall stability, plasticity in endothermic body temperature (Tb) occurs, which may facilitate maintenance of crucial activities in the face of climate change-related environmental variations. However, this plasticity may be limited by physiological or energetic constraints, which are potentially exacerbated by other environmental stressors. For instance, chemical contamination may elevate energetic costs and have endocrine disrupting effects that undermine thermoregulation. We leveraged advanced biologging techniques to elucidate how Tb varies with different behavioral states and environmental conditions in a keystone Arctic seabird, the little auk (Alle alle). We additionally evaluated whether mercury (Hg) contamination independently affected Tb, or limited or increased state-dependent changes in Tb. Tb was highest and relatively invariable when birds were at the colony, and rebounded when birds were resting on sea ice, following declines while foraging (diving) in polar waters. These results suggest that the colony and sea ice function as thermal refuges for little auks. In addition, Tb increased with ambient temperature and relative humidity across behavioral states, and increased with wind speed when birds were flying. Little auks with higher Hg levels had higher, less variable, Tb across behaviors and environmental contexts, perhaps reflecting increased metabolic rates linked to detoxification costs. Results provide evidence for environment- and contaminant-related effects on Tb, but not interactive effects between the two, and suggest that loss of sea ice and increased environmental contamination under global change may have serious implications for Tb regulation and energy balance.
Overexpression of Interleukin-8 and Interleukin-13 as potent immune markers associated with survival and dietary habits in esophageal squamous cell carcinoma

Background Interleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters. Methods Expression analysis of IL8, IL12 and IL13 were performed by Real time qPCR in blood and tumor tissue of 120 ESCC patients. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. Results When compared to normal controls, IL8 expression showed upregulation in 83% tissue samples (p=0.000) and 62% blood samples (p=0.388), IL12 expression showed upregulation in 62% tissue samples (p=0.435) and 57% blood samples (p=0.222) and IL13 expression showed upregulation in 83% tissue samples (p=0.001) and 68% blood samples (p=0.312). Significant positive correlation (p<0.05) was observed between tissue and blood level expression of IL8, IL12 and IL13. Different clinicopathological factors and dietary habits showed significant association (p<0.05) with IL8, IL12 and IL13 expression. Statistically significant positive correlation were observed for IL8 and IL13 expression in tissue as well as IL13 and IL12 expression in both tissue and blood. Also significant negative correlation of IL8 and IL12 expression in blood and tissue were also observed. Tumor stage, node stage, metastasis, consumption of betel nut, tobacco, alcohol, hot food, smoked food, spices, IL8 expression in blood, IL13 expression in tissue and IL12 expression in blood and tissue showed significant association (p<0.05) with survival of ESCC patients. Conclusions Altered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ECSS screening. Additionally, results from both survival and hazard analysis data indicate the effects of various parameters on the survival and mortality rate of ESCC patients.
Mechanotransduction events at the physiological site of touch detection

Afferents of peripheral mechanoreceptors innervate the skin of vertebrates, where they detect physical touch via mechanically gated ion channels (mechanotransducers). While the afferent terminal is generally understood to be the primary site of mechanotransduction, the functional properties of mechanically activated (MA) ionic current generated by mechanotransducers at this location remain obscure. Here, we report patch-clamp recordings from the afferent terminal innervating Grandry (Meissner) corpuscles in the bill skin of a tactile specialist duck. We show that mechanical stimulation evokes MA current in the afferent with fast kinetics of activation and inactivation during the dynamic phases of the mechanical stimulus. These responses trigger rapidly adapting firing in the afferent detected at the terminal and in the afferent fiber outside of the corpuscle. Our findings elucidate the initial electrogenic events of touch detection in the mechanoreceptor nerve terminal.
Model predictive control for Max-Plus-Linear and piecewise affine systems

This Ph.D. thesis considers the development of new analysis and control techniques for special classes of hybrid systems and discrete event systems. Two particular classes of hybrid systems (piecewise affine systems and max-min-plus-scaling systems), and two particular classes of discrete event systems (max-plus-linear systems and switching max-plus-linear systems) are studied. Using the optimal control framework, model predictive control schemes are designed that make use of the special structure of these systems and that incorporate conditions to guarantee a priori closed-loop asymptotic stability. Stability is obtained by deriving bounds on the tuning parameters or by imposing a terminal set constraint and using an appropriate terminal cost. The thesis considers three main topics: * Optimal control and model predictive control for max-plus-linear systems; * Min-max model predictive control for max-min-plus-scaling systems; * Model predictive control for piecewise affine systems.
Inherent envelope fluctuations in forward masking: Effects of age and hearing loss

Forward masking is generally greater for Gaussian noise (GN) than for low-fluctuation noise maskers, i.e., GN disruption. Because the minimal hearing loss that is associated with older age may affect GN disruption differently than more significant hearing loss, the current study explored the contribution of minimal hearing loss associated with older age to GN disruption. GN disruption was measured using three masker-signal delays (25, 75, and 150 ms) for three adult groups: younger participants with normal hearing, older participants with minimal hearing loss, and older participants with sensorineural hearing loss. The role of underlying mechanisms was tested using a computational model for midbrain neurons. The primary result suggests that older listeners with mild threshold elevations that typically occur with age may be more susceptible to the deleterious effects of masker-envelope fluctuations than younger listeners with normal hearing. Results from the computational model indicate that there may be a larger influence of efferent feedback and saturation of inner hair cells on forward masking and GN disruption than previously thought.
Associations of Microbial Diversity with Age and Other Clinical Variables among Pediatric Chronic Rhinosinusitis (CRS) Patients

Chronic rhinosinusitis (CRS) is a heterogenous disease that causes persistent paranasal sinus inflammation in children. Microorganisms are thought to contribute to the etiology and progression of CRS. Culture-independent microbiome analysis offers deeper insights on sinonasal microbial diversity and microbe-disease associations than culture-based methods. To date, CRS-related microbiome studies have mostly focused on the adult population, and only one study has characterized the pediatric CRS microbiome. In this study, we analyzed the bacterial diversity of adenoid tissue, adenoid swab, maxillary sinus, and sinus wash samples from 45 pediatric CRS patients recruited from the Johns Hopkins All Children’s Hospital (JHACH) in St Petersburg, FL, USA. The alpha diversity in these samples was associated with baseline nasal steroid use, leukotriene receptor antagonist (LTRA) use, and total serum immunoglobulin (Ig) E (IgE) level. Streptococcus, Moraxella, and Haemophilus spp. were most frequently identified from sinus cultures and the sequenced 16S rRNA gene content. Comparative analyses combining our samples with the samples from the previous microbiome study revealed differentially abundant genera between patients with pediatric CRS and healthy controls, including Cutibacterium and Moraxella. Additionally, the abundances of Streptobacillus and Staphylococcus were consistently correlated with age in both adenoid- and sinus-derived samples. Our study uncovers new associations of alpha diversity with clinical parameters, as well as associations of specific genera with disease status and age, that can be further investigated.
Retention time prediction to facilitate molecular structure identification with tandem mass spectrometry

Comparing measured and predicted chromatographic retention time can improve molecular structure assignment in applications such as coupled liquid chromatography-tandem mass spectrometry. We assess a range of different machine learning methods to predict hydrophobicity, a molecular property that can be used as a proxy for retention time. The performance of the models is evaluated on the benchmark Martel and SAMPL7 datasets. We find that more powerful models perform better when predicting in-sample but not necessarily when generalizing to out-of-sample molecular families. We also find that ensemble methods can outperform individual models. Additionally, a multitask learning model shows promise for improving the generalization ability of graph neural networks for hydrophobicity prediction. Finally, we discuss how the ability of graph neural networks to generalize for molecular property prediction could be improved further.
Disentangling leaf structural and material properties in relation to their anatomical and chemical compositional traits in oaks (Quercus L.)

The existence of sclerophyllous plants has been considered an adaptive strategy against different environmental stresses. As it literally means “hard-leaved”, it is essential to quantify the leaf mechanical properties to understand sclerophylly. However, the relative importance of each leaf trait on mechanical properties is not yet well established. The genus Quercus is an excellent system to shed light on this since it minimizes phylogenetic variation while having a wide variation in sclerophylly. Thus, leaf anatomical traits and cell wall composition were measured, analyzing their relationship with LMA and leaf mechanical properties in a set of 25 oak species. Outer wall contributed strongly to leaf mechanical strength. Moreover, cellulose plays a critical role in increasing leaf strength and toughness. The PCA plot based on leaf trait values clearly separated Quercus species into two groups corresponding to evergreen and deciduous species. Sclerophyllous Quercus species are tougher and stronger due to their thicker epidermis outer wall and/or higher cellulose concentration. Furthermore, section Ilex species share common traits regardless of they occupy quite different climates. In addition, evergreen species living in Mediterranean-type climates share common leaf traits irrespective of their different phylogenetic origin.
Biostatistics and its impact on hazard characterization using in vitro developmental neurotoxicity assays

In the field of hazard assessment, Benchmark concentrations (BMC) and their associated uncertainty are of particular interest for regulatory decision making. The BMC estimation consists of various statistical decisions to be made, which depend largely on factors such as experimental design and assay endpoint features. In current data practice, the experimenter is often responsible for the data analysis and therefore relies on statistical software without being aware about the software default settings and how they can impact the outputs of data analysis. To provide more insight into how statistical decision making can influence the outcomes of data analysis and interpretation, we have used case studies on a large dataset produced by a developmental neurotoxicity (DNT) in vitro battery (DNT IVB). Here we focused on the BMC and its confidence interval (CI) estimation, as well as on the final hazard classification. We identified five crucial statistical decisions experimenter have to face during data analysis: choice of replicate averaging, response data normalization, regression modelling, BMC and CI estimation, as well as choice of benchmark response levels. In addition, the strength of our data evaluation platform is the integration of endpoint-specific hazard classifications, including flagging systems for uncertain cases, which none of the so far existing statistical data analysis platforms provide. The insights gained in this study demonstrate how important fit-for-purpose, internationally harmonized and accepted data evaluation and analysis procedures are for an objective hazard classification.
Facilitatory stimulation of the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity

Background The continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. Methods We implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, we stimulated each participant once with effective and once with sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. Results Effective stimulation increased activation relative to sham stimulation only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased functional connectivity in task-specific networks for semantic and executive conditions with high cognitive load. Notably, stimulation-induced changes in activation and connectivity related differently to behavior: While increased activation of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. Conclusions iTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.