Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphatidylinositol 4,5-bisphosphate drives Ca 2 (cid:2) -independent membrane penetration by the tandem C2 domain proteins synaptotagmin-1 and Doc2 (cid:3)

Exocytosis mediates the release of neurotransmitters and hormones from neurons and neuroendocrine cells. Tandem C2 domain proteins in the synaptotagmin (syt) and double C2 domain (Doc2) families regulate exocytotic membrane fusion via direct interactions with Ca 2 (cid:2) and phospholipid bilayers. Syt1 is a fast-acting, low-affinity Ca 2 (cid:2) sensor that penetrates membranes upon binding Ca 2 (cid:2) to trigger synchronous vesicle fusion. The closely related Doc2 (cid:3) is a slow-acting, high-affinity Ca 2 (cid:2) sensorthattriggersspontaneousandasynchronousvesicle fusion, but whether it also penetrates membranes is unknown. Both syt1 and Doc2 (cid:3) the dynamically regulated plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ), but it is unclear whether PIP 2 serves only as a membrane contact or enables specialized membrane-binding modes by these Ca 2 (cid:2) sensors. Furthermore, it has been shown that PIP 2 uncaging can trigger rapid, syt1-dependent exocytosis in the absence of Ca 2 (cid:2) influx, suggesting that current models for the action of these Ca 2 (cid:2) sensors are incomplete. using a series of steady-state and time-resolved fluorescence measurements, we syt1, Ca (cid:2) in the absence of Ca 2 (cid:2) , providing a plausible mechanism for Ca 2 (cid:2) -independent, PIP 2 -dependent exocytosis. Quantitative measurements of provide and some
Ultrasound to guided epicutaneo-caval catheter insertion in newborn infants

Objective Recently, ultrasound (US) has been increasingly used for epicutaneo-caval catheter (ECC) tip positioning; however, the selection of blood vessels for ECC still depends on the operator’s subjective judgment. This study aimed to explore the value of US in decision-making regarding the great saphenous vein (GSV), tip navigation, and tip location of ECC. Methods Catheterization through the GSV of the lower extremity was selected. The running condition of the GSV was assessed by using US, and the angle between the GSV and the femoral vein was observed and measured. We selected the GSV with a smaller angle to the femoral vein for ECC catheterization. Results ECC catheterization under ultrasound guidance increased the success rate at the time of catheterization from 82.5% to 100% (increased by 17.5%) and shortened the catheterization time from 56.1 ± 5.30 min to 31.5 ± 2.58 min on average (shortened by 44%). The incidence rate of catheter-related complications decreased by 58.2% catheter days from 6.80/1,000 to 2.84/1,000. Conclusion ECC insertion under the guidance of US has numerous advantages, including significantly improving the success rate of one-time catheterization, shortening the time of catheterization, and reducing catheter-related complications.
Mapping family connectedness across space and time

Understanding the structure and evolution of family networks embedded in space and time is crucial for various fields such as disaster evacuation planning and provision of care to the elderly. Computation and visualization can potentially play a key role in analyzing and understanding such networks. Graph visualization methods are effective in discovering network patterns; however, they have inadequate capability in discovering spatial and temporal patterns of connections in a network especially when the network exists and changes across space and time. We introduce a measure of family connectedness that summarizes the dynamic relationships in a family network by taking into account the distance (how far individuals live apart), time (the duration of individuals’ coexistence within a neighborhood), and the relationship (kinship or kin proximity) between each pair of individuals. By mapping the family connectedness over a series of time intervals, the method facilitates the discovery of hot spots (hubs) where family connectedness is strong and the changing patterns of such spots across space and time. We demonstrate our approach using a data set of nine families from the US North. Our results highlight that family connectedness reflects changing demographic processes such as migration and population growth.
Human occupational intensity and palaeoecology at Klasies River from MIS 5–3: Preliminary taphonomic analyses of faunal remains from the Deacon and Wurz excavations

Klasies River is a key site in understanding the behaviour of coastal foragers in the southern Cape of South Africa. Faunal remains from Klasies River, recovered from an almost 70,000 year sequence over the Late Pleistocene, are a valuable dataset in investigating subsistence and occupational dynamics, yet few taphonomic studies have been conducted on the fauna from Klasies River. Here, the first taphonomic analyses of faunal remains from the Deacon and Wurz excavation is presented. The aim of this paper is to link occupational patterns during the Late Pleistocene at Klasies River with coastal ecology using taxonomic data from previous studies, and recently analysed taphonomic data. Taphonomic analyses of samples from the MSA II Lower, the Howiesons Poort and the MSA III periods were used to examine occupational intensity based on proportions of anthropogenic and zoogenic bone surface modification, trampling marks, transverse fractures and faunal density. Declining foraging efficiency or subsistence intensification was also investigated using indicators for expanded diet breadth (e.g., small fauna exploitation and increases in juveniles), more intensive marrow extraction and evidence for greater foraging distances. Herbivore functional types and dietary preferences were examined using taxonomic data and these show three main ecological phases at Klasies River: the MSA I; the upper and lower MSA II; and the HP and MSA III phases. Taphonomic data show increased occupational intensity in the MSA II Lower, with subsistence intensification also more evident here than other layers. Trampling data suggests that occupational intensity was greater in the earlier Howiesons Poort than later phase with little evidence of declining foraging efficiency then. The data indicate that, while humans contributed significantly to the MSA III assemblage, carnivores were the main accumulators here suggesting lower occupational intensity in this phase. The results of this study shows a possible link between increased occupational intensity and declining foraging efficiency at Klasies River but larger taphonomic samples are needed to explore this relationship further.
Advances in platinum-based and platinum-free oxygen reduction reaction catalysts for cathodes in direct methanol fuel cells

Direct methanol fuel cells (DMFCs) have been the focus of future research because of their simple structure, abundant fuel sources, high energy conversion efficiency and low cost. Among the components in DMFC, the activity and stability of the cathode catalyst is the key to the performance and lifetime of the DMFCs. Oxygen reduction reaction (ORR) is an important electrode reaction on DMFC cathode. It is known that Pt is widely used in the fabrication of ORR catalysts, but the limited earth storage of Pt and its high price limit the use of Pt-based commercial catalysts in DMFCs. To overcome these problems, advances have been made on new low Pt-based catalysts and Pt-free catalysts in recent years. In this article, the development of novel ORR catalysts and the carbon supports is reviewed and discussed.
Study of the anticancer effect of new quinazolinone hydrazine derivatives as receptor tyrosine kinase inhibitors

The advent of novel receptor tyrosine kinase inhibitors has provided an important therapeutic tool for cancer patients. In this study, a series of quinazolinone hydrazide triazole derivatives were designed and synthesized as novel MET (c-MET) receptor tyrosine kinase inhibitors. The antiproliferative effect of the synthesized compounds was examined against EBC-1, A549, HT-29 and U-87MG cells by MTT assay. MET kinase inhibitory effect was tested by a Homogenous Time Resolved Fluorescence (HTRF) assay. The antiproliferative effect of compounds in a three-dimensional spheroid culture was studied by acid phosphatase (APH) assay, while apoptosis induction was examined by Hoechst 33258 staining. We found that compound CM9 bearing p-bromo benzyl pendant inhibited MET kinase activity at the concentrations of 10–50 μM (% Inhibition = 37.1–66.3%). Compound CM9 showed antiproliferative effect against cancer cells, in particular lung cancer cells with MET amplification (EBC-1) with an IC50 value of 8.6 μM. Moreover, this derivative inhibited cell growth in spheroid cultures in a dose-dependent manner and induced apoptosis in cancer cells. Assessment of inhibitory effect of CM9 against a panel of 18 different protein kinases demonstrated that this compound also inhibits ALK, AXL, FGFR1, FLT1 (VEGFR1) and FLT4 (VEGFR3) more than 50% at 25 μM. Finally, molecular docking and dynamics simulation corroborated the experimental findings and showed critical structural features for the interactions between CM9 and target kinases. The findings of this study present quinazolinone hydrazide triazole derivatives as kinase inhibitors with considerable anticancer effects.
“Doing good and feeling good” Relationship between authentic leadership with followers' work engagement: The mediating role of hedonic and eudaimonic wellbeing

The positive behavioral style of authentic leadership has attracted academicians' and practitioners' attention to focus more on a healthy workplace environment and its influence on followers' valued workplace relationship outcomes, such as employees' work engagement. From the lens of social exchange perspective, we tested a unified model of authentic leadership and its influence on the followers' wellbeing (hedonic and eudaimonic wellbeing) and work engagement. We also examined the mediating role of hedonic and eudaimonic wellbeing on followers' work engagement. Using a time-lagged design, we collected data from 250 telecom sector workers employed in the capital city of Islamabad, Pakistan. The results indicate the positive influence of authentic leadership on followers' work engagement and employees' hedonic and eudaimonic wellbeing. Hedonic and eudaimonic wellbeing also positively mediated the relationship between authentic leadership and followers' work engagement. The theoretical and practical implications of the study are also discussed.
Dust Production Rates in the Fomalhaut Debris Disk from SOFIA/FORCAST Mid-infrared Imaging

We present the first spatially resolved mid-infrared (37.1 μm) image of the Fomalhaut debris disk. We use point spread function fitting and subtraction to distinctly measure the flux from the unresolved component and the debris disk. We measure an infrared excess in the point source of 0.9 ± 0.2 Jy, consistent with emission from warm dust in an inner disk structure, and inconsistent with a stellar wind origin. We cannot confirm or rule out the presence of a pileup ring near the star. In the cold region, the 37 μm imaging is sensitive to emission from small, blowout grains, which is an excellent probe of the dust production rate from planetesimal collisions. Under the assumptions that the dust grains are icy aggregates and the debris disk is in steady state, this result is consistent with the dust production rates predicted by Kenyon & Bromley from theoretical models of icy planet formation. We find a dust luminosity of (7.9 ± 0.8) × 10−4 L⊙ and a dust mass of 8–16 lunar masses, depending on grain porosity, with ∼1 lunar mass in grains with radius 1 μm–1 mm. If the grains are icy and highly porous, meter-sized objects must be invoked to explain the far-infrared, submm, and mm emission. If the grains are composed of astronomical silicates, there is a dearth of blowout grains and the mass loss rate is well below the predicted dust production values.
Mismatch negativity–stimulation paradigms in past and in future

Mismatch negativity (MMN) studies were initiated as part of a well-controlled experimental research tradition with the aim to identify some key principles of auditory processing and memory. During the past two decades, empirical paradigms have moved toward more ecologically valid ones while retaining rigid experimental control. In this paper, I will introduce this development of MMN stimulation paradigms starting from the paradigms used in basic science and then moving to paradigms that have been particularly relevant for studies on music learning and musical expertise. Via these historical and thematic perspectives, I wish to stimulate paradigm development further to meet the demands of naturalistic ecologically valid studies also when using MMN in the context of event-related potential technique that necessarily requires averaging across several stimulus presentations.
In silico assessment of pharmacotherapy for carbon monoxide induced arrhythmias in healthy and failing human hearts

Background: Carbon monoxide (CO) is gaining increased attention in air pollution-induced arrhythmias. The severe cardiotoxic consequences of CO urgently require effective pharmacotherapy to treat it. However, existing evidence demonstrates that CO can induce arrhythmias by directly affecting multiple ion channels, which is a pathway distinct from heart ischemia and has received less concern in clinical treatment. Objective: To evaluate the efficacy of some common clinical antiarrhythmic drugs for CO-induced arrhythmias, and to propose a potential pharmacotherapy for CO-induced arrhythmias through the virtual pathological cell and tissue models. Methods: Two pathological models describing CO effects on healthy and failing hearts were constructed as control baseline models. After this, we first assessed the efficacy of some common antiarrhythmic drugs like ranolazine, amiodarone, nifedipine, etc., by incorporating their ion channel-level effects into the cell model. Cellular biomarkers like action potential duration and tissue-level biomarkers such as the QT interval from pseudo-ECGs were obtained to assess the drug efficacy. In addition, we also evaluated multiple specific I Kr activators in a similar way to multi-channel blocking drugs, as the I Kr activator showed great potency in dealing with CO-induced pathological changes. Results: Simulation results showed that the tested seven antiarrhythmic drugs failed to rescue the heart from CO-induced arrhythmias in terms of the action potential and the ECG manifestation. Some of them even worsened the condition of arrhythmogenesis. In contrast, I Kr activators like HW-0168 effectively alleviated the proarrhythmic effects of CO. Conclusion: Current antiarrhythmic drugs including the ranolazine suggested in previous studies did not achieve therapeutic effects for the cardiotoxicity of CO, and we showed that the specific I Kr activator is a promising pharmacotherapy for the treatment of CO-induced arrhythmias.
Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model

The vascular endothelium plays a pivotal role in the maintenance of vascular homeostasis, mediated by vasoactive molecules produced by endothelial cells. The balance between vasoconstrictor and vasodilator biomolecules is what guarantees this equilibrium. Therefore, an increase in the bioavailability of vasoconstrictors along with a reduction in vasodilators may indicate a condition known as endothelial dysfunction. Endothelial dysfunction is marked by an inflammatory process and reduced activity of vasoprotective enzymes, being characterized by some factors like the reduction of the bioavailability of nitric oxide (NO) and increase in the production of reactive oxygen species (ROS), pro-inflammatory and vasoconstrictor molecules. This condition is a predictive marker of several cardiovascular diseases (e.g., atherosclerosis, hypertension, and diabetes). Research is affected by the scarcity of suitable in vitro models that simulate endothelial dysfunction. The goal of this study was to induce an in vitro condition to mimic endothelial dysfunction by inhibiting NO synthesis in cells. Thymus-derived endothelial cells (tEnd.1) were treated with different concentrations of L-NAME (from 1 to 1,000 μM) for different times (12, 24, 48, 72, 96, and 120 h without and with retreatment every 24 h). Cell viability, nitrite concentration, p22phox, NOX2, NOX4, IL-6, and ACE genes expression and lipid peroxidation were evaluated. The results indicate that the treatment with 100 μM L-NAME for 72 h without retreatment reduced NO concentration and NOX4 gene expression while increasing ACE expression, thus mimicking reduced vascular protection and possibly increased vasoconstriction. On the other hand, treatment with 100 μM L-NAME for 96 h with retreatment reduced the concentration of NO and the expression of the p22phox gene while increasing the expression of the IL-6 and ACE genes, mimicking the increase in inflammation and vasoconstriction parameters. Based on these results, we thus propose that both 100 μM L-NAME for 72 h without retreatment and 100 μM L-NAME for 96 h with retreatment may be used as models for in vitro endothelial dysfunction according to the purpose of the study to be conducted.
Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study

Background and objective: Vascular cognitive impairment (VCI) can be caused by multiple types of cerebrovascular pathology and is considered a network disconnection disorder. The heterogeneity hinders research progress in VCI. Glymphatic failure has been considered as a key common pathway to dementia recently. The emergence of a new method, Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), makes it possible to investigate the changes of the glymphatic function in humans non-invasively. We aimed to investigate alterations of glymphatic function in VCI and its potential impact on network connectivity. Methods: We recruited 79 patients with mild VCI, including 40 with cerebral small vessel disease cognitive impairment (SVCI) and 39 with post-stroke cognitive impairment (PSCI); and, 77 normal cognitive (NC) subjects were recruited. All subjects received neuropsychological assessments and multimodal magnetic resonance imaging scans. ALPS-index was calculated and structural networks were constructed by deterministic tractography, and then, the topological metrics of these structural connectivity were evaluated. Results: The ALPS-index of VCI patients was significantly lower than that of NC subjects (P < 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (β = 0.411, P < 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (r = −0.263, P = 0.001) and multiple cerebrovascular pathologies (P < 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (r = 0.348, P = 0.028) and PSCI (r = 0.732, P < 0.001) patients. Finally, the results of mediation analysis showed that Eg partially mediated in the impact of glymphatic dysfunction on cognitive impairment (indirect effect = 7.46, 95% CI 4.08–11.48). Conclusion: In both major subtypes of VCI, the ALPS-index was decreased, indicating impaired glymphatic function in VCI. Glymphatic dysfunction may affect cognitive function in VCI by disrupting network connectivity, and, may be a potential common pathological mechanism of VCI. ALPS-index is expected to become an emerging imaging marker for VCI.
Non-thermal afterglow of the binary neutron star merger GW170817: a more natural modelling of electron energy distribution leads to a qualitatively different new solution

The observed nonthermal afterglow spectrum of the binary neutron star (BNS) merger GW170817 from radio to X-ray are consistent with synchrotron radiation by shock-accelerated electrons. However, previous afterglow modeling studies were based on a simplified assumption that the acceleration efficiency is extremely high, i.e. all electrons in the shock are accelerated as a nonthermal population. This affects the estimate of the minimum electron energy and hence $\nu_m$, the peak frequency of the afterglow spectrum. Here we present Bayesian fitting to the observed data with a more natural electron energy distribution, in which the acceleration efficiency is a free parameter. Interestingly, the maximum likelihood solutions are found with radio flux below $\nu_m$ in the early phase, in contrast to previous studies that found the radio frequency always above $\nu_m$. Therefore the $\nu_m$ passage through the radio band could have been clearly detected for GW170817, if sufficient low-frequency radio data had been taken in early time. In the new solutions, the lowest energy of electrons is found close to equipartition with the post shock protons, but only a small fraction ($<$10\%) of electrons are accelerated as nonthermal particles. The jet energy and interstellar medium density are increased by 1--2 orders of magnitude from the conventional modeling, though these are still consistent with other constraints. We encourage to take densely sampled low-frequency radio data in the early phase for future BNS merger events, which would potentially detect $\nu_m$ passage and give a strong constraint on electron energy distribution and particle acceleration efficiency.
School ethnic-racial socialization and critical action among Black youth

We explore the interaction of different types of school ethnic-racial socialization, youth’s perceptions of the messages that schools and their agents broadcast about race and ethnicity, as it shapes Black youth’s critical action, the individual and collective action that youth engage in to combat oppression and racism. In particular, the co-occurrence of critical consciousness socialization (emphasizes racial inequity; CCS), cultural socialization (celebrates youth’s culture/s; CS), and color evasive socialization (de-emphasizes and thus delegitimizes the importance of race; CES) are explored. The adaptive culture and Mustaffa’s conceptualization of Black lifemaking, an aspect of freedom dreaming in which Black people define and care for themselves in ways (such as critical action) that counter dominant, anti-Black ideologies, serve as the overarching theoretical frameworks. As both the adaptive culture paradigm and critical action necessitate a target of resistance, we hypothesize that CES, in providing Black youth something to resist against, may actually serve as a positive moderator between CCS and/or CS and their critical action. We investigate these questions among a sample of Black adolescents (n = 285, M = 15.09 years, and SD = 1.38 years). Benjamini–Hochberg corrected hierarchical moderations with age as a covariate and socialization type and interaction between types as predictors revealed that the interaction between CCS and CES significantly predicted critically conscious action [β = 0.25, SE = 0.08, t(193) = 2.54, and p < 0.05] and political anti-racist action [β = 0.21, SE = 0.09, t(193) = 2.38, and p < 0.05]. Critically conscious action was more frequent among Black youth who perceived greater CES. The relationship between CCS and political anti-racist action was stronger among those who perceived greater CES. These findings may provide comfort to those worried about CES’ impact. Black youth simultaneously socialized with CCS seem to develop a critical consciousness that allows them to trouble CES and to be critically active despite it. Engaging in varied, frequent critical action allows Black youth to continue the life-making which improves the Black American experience and drives their freedom dreaming.