Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-Energy Collisions of Zeeman-Decelerated NH Radicals with He Atoms

We report an experimental study of state-to-state inelastic scattering of NH (X 3Σ–, N = 0, j = 1) radicals with He atoms. Using a crossed molecular beam apparatus that combines a Zeeman decelerator and velocity map imaging, we study both integral and differential cross sections in the N = 0, j = 1 → N = 2, j = 3 inelastic channel. We developed various new REMPI schemes to state-selectively detect NH radicals, and tested their performance in terms of sensitivity and ion recoil velocity. We found a 1 + 2′ + 1′ REMPI scheme using the A 3Π ← X 3Σ– resonant transition, which yields acceptable recoil velocities and is more than an order of magnitude more sensitive than conventional one-color REMPI schemes to detect NH. We used this REMPI scheme to probe state-to-state integral and differential cross sections around the channel opening at 97.7 cm–1, as well as at higher energies where structure in the scattering images could be resolved. The experimental results are in excellent agreement with the predictions from quantum scattering calculations which are based on an ab initio NH-He potential energy surface.
Arterial stiffness and blood pressure in treated hypertension: a longitudinal study

Objectives: It has been reported that an increase in arterial stiffness precedes an increase in blood pressure (BP) in the general population. Whether BP lowering results from of reducing arterial wall or vice versa in antihypertensive treatment is unclear. This study aimed to investigate the association between arterial stiffness and BP in patients with treated hypertension. Methods: This study included 3277 participants who were treated with antihypertensive agents and with repeated measurements of branchial-ankle pulse wave velocity (baPWV) and BP during 2010–2016 from the Kailuan study. Temporal relation between baPWV and BP was assessed by cross-lagged path analyses. Results: After adjustment for potential confounders, the standard regression coefficient from baseline baPWV to follow-up SBP was 0.14 [95% confidence interval (95% CI), 0.10–0.18], which was significantly greater than that from baseline SBP to follow-up baPWV (0.05; 95% CI, 0.02–0.08) (P < 0.0001 for difference). Similar results were observed for the cross-lagged analysis with changes of baPWV and mean arterial pressure. Further analysis showed that the yearly rate of change in SBP during the follow-up period significantly varied across increasing quartiles of baseline baPWV (P < 0.0001), whereas the yearly rate of change in baPWV showed a nonsignificantly varied trend across quartiles of baseline SBP (P = 0.2443). Conclusion: These findings provided strong evidence that reduction in arterial stiffness through antihypertensive treatment could precede BP lowering.
Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia

Abstract Frontotemporal dementia is clinically and neuropathologically heterogeneous, but neuroinflammation, atrophy and cognitive impairment occur in all of its principal syndromes. Across the clinical spectrum of frontotemporal dementia, we assess the predictive value of in vivo neuroimaging measures of microglial activation and grey-matter volume on the rate of future cognitive decline. We hypothesized that inflammation is detrimental to cognitive performance, in addition to the effect of atrophy. Thirty patients with a clinical diagnosis of frontotemporal dementia underwent a baseline multimodal imaging assessment, including [11C]PK11195 PET to index microglial activation and structural MRI to quantify grey-matter volume. Ten people had behavioural variant frontotemporal dementia, 10 had the semantic variant of primary progressive aphasia and 10 had the non-fluent agrammatic variant of primary progressive aphasia. Cognition was assessed at baseline and longitudinally with the revised Addenbrooke's Cognitive Examination, at an average of 7-month intervals (for an average of ∼2 years, up to ∼5 years). Regional [11C]PK11195 binding potential and grey-matter volume were determined, and these were averaged within four hypothesis-driven regions of interest: bilateral frontal and temporal lobes. Linear mixed-effect models were applied to the longitudinal cognitive test scores, with [11C]PK11195 binding potentials and grey-matter volumes as predictors of cognitive performance, with age, education and baseline cognitive performance as covariates. Faster cognitive decline was associated with reduced baseline grey-matter volume and increased microglial activation in frontal regions, bilaterally. In frontal regions, microglial activation and grey-matter volume were negatively correlated, but provided independent information, with inflammation the stronger predictor of the rate of cognitive decline. When clinical diagnosis was included as a factor in the models, a significant predictive effect was found for [11C]PK11195 BPND in the left frontal lobe (−0.70, P = 0.01), but not for grey-matter volumes (P > 0.05), suggesting that inflammation severity in this region relates to cognitive decline regardless of clinical variant. The main results were validated by two-step prediction frequentist and Bayesian estimation of correlations, showing significant associations between the estimated rate of cognitive change (slope) and baseline microglial activation in the frontal lobe. These findings support preclinical models in which neuroinflammation (by microglial activation) accelerates the neurodegenerative disease trajectory. We highlight the potential for immunomodulatory treatment strategies in frontotemporal dementia, in which measures of microglial activation may also improve stratification for clinical trials.
Supply chain resilience in the Colombian defense sector before and during the COVID-19 pandemic: A comparative study

Unforeseen events can significantly affect organizations’ supply chains and disrupt their continuous flow. Therefore, organizations need to develop a response capability that allows them to minimize the negative effect of such events and quickly recover from them, also known as resilience. This research performs a comparative analysis of the influence that risk, vulnerability, and adaptability have on the resilience capability of supply chains in Colombian defense sector organizations before and during the coronavirus outbreak. Based on a literature review, a survey was designed and applied online to collect data from respondents related to the activities of the Colombian Air Force supply chain. For the first wave, data was collected between December 2019 and January 2020. Data for the second wave was collected in August 2020. Results suggest that identifying and managing risks positively impact reducing vulnerability and increasing adaptability. Moreover, by decreasing exposure and improving adaptability, the organization positively influences supply chain resilience capability. The results also indicate that the pandemic positively affected risk and vulnerability awareness. The identification of vulnerabilities had a positive impact on the resilience capacity during the Corona Virus outbreak. This research provides relevant information for the Colombian government on developing public policies and mechanisms of service and support for defense sector organizations to strengthen their resilience capability. Likewise, the study offers valuable information to those organizations interested in improving their resilience capability and that of the sector in which they are involved.
Apoptotic, cytotoxic, antioxidant, and antibacterial activities of biosynthesized silver nanoparticles from nettle leaf

Here, we reported the biosynthesis of silver nanoparticles (AgNPs) using Urtica dioica (nettle) leaf extract as green reducing and capping agents and investigate their anticancer and antibacterial, activity. The Nettle‐mediated biosynthesized AgNPs was characterized by UV–Vis a spectrophotometer. Their size, shape and elemental analysis were determined with the using of SEM and TEM. The crystal structure was determined by XRD and the biomolecules responsible for the reduction of Ag+ were determined using FTIR analysis. Nettle‐mediated biosynthesis AgNPs indicated strong antibacterial activity against pathogenic microorganisms. Again, the antioxidant activity of AgNPs is quite high when compared to ascorbic acid. Anticancer effect of AgNPs, IC50 dose was determined by XTT analysis using MCF‐7 cell line and the IC50 value was found to be 0.243 ± 0.014 μg/mL (% w/v).
Architecture of head and neck soft tissues and associated entheses: An exploration of sexual dimorphism in, and population differences between, New Zealand and Thai individuals

Understanding the musculoskeletal anatomy of soft tissues of the head and neck is important for surgical applications, biomechanical modelling and management of injuries, such as whiplash. Additionally, analysing sex and population differences in cervical anatomy can inform how biological sex and population variation may impact these anatomical applications. Although some muscles of the head and neck are well‐studied, there is limited architectural information that also analyses sex and population variation, for many small cervical soft tissues (muscles and ligaments) and associated entheses (soft tissue attachment sites). Therefore, the aim of this study was to present architectural data (e.g., proximal and distal attachment sites, muscle physiological cross‐sectional area, ligament mass, enthesis area) and analyse sex and population differences in soft tissues and entheses associated with sexually dimorphic landmarks on the cranium (nuchal crest and mastoid process) and clavicle (rhomboid fossa). Through the dissection and three‐dimensional analysis of 20 donated cadavers from New Zealand (five males, five females; mean age 83 ± 8 years; range 67–93 years) and Thailand (five males, five females; 69 ± 13 years; range 44–87 years), the following soft tissues and their associated entheses were analysed: upper trapezius, semispinalis capitis and the nuchal ligament (nuchal crest); sternocleidomastoid, splenius capitis and longissimus capitis (mastoid process); the clavicular head of pectoralis major, subclavius, sternohyoid and the costoclavicular (rhomboid) ligament (rhomboid fossa). Findings indicate that although muscle, ligament and enthesis sizes were generally similar to previously published data, muscle size was smaller for six of the eight muscles in this study, with only the upper trapezius and subclavius demonstrating similar values to previous studies. Proximal and distal attachment sites were largely consistent with the current research. However, some individuals (six of 20) had proximal upper trapezius attachments on the cranium, with most attaching solely to the nuchal ligament, contrasting with existing literature, which often describes attachment to the occipital bone. With respect to sexual dimorphism, the Thai sample exhibited more sex differences in muscle size than the New Zealand sample, but for enthesis size (area), both samples had the same amount of statistically significant sex differences (5 of 10). Additionally, some significant population differences were found when comparing muscle and enthesis size data between the New Zealand and Thai samples. Despite these findings, no sex or population differences were found for ligament size (mass) in either group. This paper presents new architectural data for several understudied areas of the head and neck, as well as providing analyses on sex and population differences, two areas that have limited representation in anatomy.
Taxonomic re-evaluation of African anuran trypanosomes with the redescription and molecular diagnosis of Trypanosoma (Trypanosoma) nelspruitense Laveran, 1904 and Trypanosoma (Haematomonas) grandicolor Pienaar, 1962

Abstract Abstract The aquatic and terrestrial clades of species of Trypanosoma could provide insight into the evolutionary history of the genus, as well as complementary information for biomedical studies of medically and economically important species of Trypanosoma. The ecological interactions and phylogeny of aquatic trypanosomes are currently not well-understood, mostly due to their complex life cycles and a deficiency of data. The species of Trypanosoma from African anuran hosts are of the least understood taxa in the genus. Trypanosomes were collected from South African frogs and subjected to morphological and phylogenetic analyses. This study redescribes Trypanosoma (Trypanosoma) nelspruitense Laveran, 1904 and Trypanosoma (Haematomonas) grandicolor Pienaar, 1962, with morphological and molecular data. The present study aims to create a platform for further future research on African anuran trypanosomes.
A framework for epistemic uncertainty quantification of turbulent scalar flux models for Reynolds-averaged Navier-Stokes simulations

Reynolds-averaged Navier-Stokes (RANS) simulations are a practical approach for solving complex multi-physics turbulent flows, but the underlying assumptions of the turbulence models introduce errors and uncertainties in the simulation outcome. The flow in scramjet combustors is an example of such a complex flow and the accurate characterization of safety and operability limits of these engines using RANS simulations requires an assessment of the model uncertainty. The objective of this paper is to present a framework for the epistemic uncertainty quantification of turbulence and mixing models in RANS simulations. The capabilities of the methodology will be demonstrated by performing simulations of the mixing of an underexpanded jet in a supersonic cross flow, which involves many flow features observed in scramjet engines. The fundamental sources of uncertainty in the RANS simulations are the models used for the Reynolds stresses in the momentum equations and the turbulent scalar fluxes in the scalar tran.
Chemistry, structure and function of approved oligonucleotide therapeutics

Abstract Eighteen nucleic acid therapeutics have been approved for treatment of various diseases in the last 25 years. Their modes of action include antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi) and an RNA aptamer against a protein. Among the diseases targeted by this new class of drugs are homozygous familial hypercholesterolemia, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary transthyretin-mediated amyloidosis, familial chylomicronemia syndrome, acute hepatic porphyria, and primary hyperoxaluria. Chemical modification of DNA and RNA was central to making drugs out of oligonucleotides. Oligonucleotide therapeutics brought to market thus far contain just a handful of first- and second-generation modifications, among them 2′-fluoro-RNA, 2′-O-methyl RNA and the phosphorothioates that were introduced over 50 years ago. Two other privileged chemistries are 2′-O-(2-methoxyethyl)-RNA (MOE) and the phosphorodiamidate morpholinos (PMO). Given their importance in imparting oligonucleotides with high target affinity, metabolic stability and favorable pharmacokinetic and -dynamic properties, this article provides a review of these chemistries and their use in nucleic acid therapeutics. Breakthroughs in lipid formulation and GalNAc conjugation of modified oligonucleotides have paved the way to efficient delivery and robust, long-lasting silencing of genes. This review provides an account of the state-of-the-art of targeted oligo delivery to hepatocytes.
Evaluation of headstarting as a conservation tool to recover Blanding’s Turtles (Emydoidea blandingii) in a highly fragmented urban landscape

Freshwater turtle populations are declining globally as a result of anthropogenic activities. Threats to turtles in urban areas are exacerbated by road mortality and subsidized predators, which can lead to catastrophic shifts in population size and structure. Headstarting is used as a conservation tool to supplement turtle populations that may otherwise face extirpation. A headstarting program began in 2012 to recover a functionally extinct population of Blanding’s Turtles (Emydoidea blandingii) 26in Rouge National Urban Park (RNUP), Ontario, Canada. The original population included five adults and one juvenile turtle. From 2014 to 2020, 270 headstarted turtles were released. The population has been monitored annually since 2014 using visual-encounter surveys, radio-telemetry, and live trapping (from 2018 onwards). We used mark-recapture and radio-telemetry data to quantify abundance, survival, and sex ratio of the headstarted turtle population. Using a Jolly-Seber model, we estimated abundance to be 183 turtles (20 turtles/ha) in 2020. Estimated survival of headstarted turtles approached 89%, except for turtles released in 2019 when survival was 43% as a result of a known mass mortality event at the study site. Pre- and post-release sex ratios were not significantly different (χ2 = 1.92; p = 0.16), but shifted from 1:1.5 to 1:1 male:female post-release. Given that the headstarted turtles have not yet reached sexual maturity, it is unclear whether headstarted turtles will reach adulthood and successfully reproduce to maintain a self-sustaining population. Thus, to evaluate the success of the headstarting program, long-term monitoring is required.
Tree species composition along environmental and disturbance gradients in tropical sub-montane forests, Tanzania

Understanding the environmental and disturbance determinants of tree species dominance and community composition in an ecosystem, is important for informing management and conservation decisions, through maintaining or improving the existing forest composition and structure. This study was carried out to quantify the relationship between forest tree composition structure and environmental and disturbance gradients, in a tropical sub-montane forest of Eastern Usambara. Vegetation, environmental, and anthropogenic disturbance data for 58 plots across Amani and Nilo nature forest reserves were obtained. Agglomerative hierarchical cluster analysis and canonical correspondence analysis (CCA) were used to identify plant communities and analyze the influence of environmental variables and anthropogenic disturbances on tree species and community composition respectively. Four communities were identified and CCA results showed that the variation was significantly related to elevation, pH, Annual mean temperature, temperature seasonality, phosphorus nutrients and pressures from adjacent villages and roads. Likewise, environmental factors (climate, soil and topography) explained the most variation (14.5%) of tree and community composition in relation to disturbance pressure (2.5%). The large and significant variation in tree species and community patterns explained by environmental factors suggests a need for site-specific assessment of environmental properties for biodiversity conservation plans. Similarly, the intensification of human activities and associated impacts on natural environment should be minimized to maintain forest species composition patterns and communities. The findings are useful in guiding in policy interventions that focus on minimizing human disturbances in the forests and could aid in preserving and restoring the functional organization and tree species composition of the sub-tropical montane forests.
The nuclear isoforms of the Fragile X mental retardation RNA-binding protein associate with genomic DNA bridges

The fragile-X mental retardation protein (FMRP) is a canonical RNA-binding protein whose absence in humans leads to the development of the fragile-X syndrome, characterized by multiple phenotypes including neurodevelopmental disorders, intellectual disability, autism, and macroorchidism. The primary transcripts of the FMR1 gene undergo extensive alternative splicing processes, and multiple protein isoforms are produced. The predominantly cytoplasmic isoforms are translational regulators, while the roles of the nuclear ones have been neglected. In this study, we discovered that nuclear FMRP isoforms specifically associate with DNA bridges, aberrant genomic structures that form during mitosis and whose accumulation can drive genome instability by inducing DNA damage. Further localization studies showed that a subset of FMRP-positive bridges contain proteins that have been shown to associate with specific DNA bridges known as ultrafine DNA bridges (UFBs) and surprisingly are RNA positive. Significantly, the depletion of nuclear FMRP isoforms promotes the accumulation of DNA bridges, correlating with the accumulation of DNA damages and cell death, unveiling an important function of these neglected isoforms.
Bisulfite probing reveals DNA structural intricacies

Abstract In recent decades, study of DNA structure has largely been focused on the interrelationships between nucleotides at the level of nearest neighbours. A little-utilized approach to probing structure on a larger scale is non-denaturing bisulfite modification of genomic DNA in conjunction with high-throughput sequencing. This technique revealed a marked gradient in reactivity increasing towards the 5′ end of poly-dC:dG mononucleotide repeats as short as two base pairs, suggesting that access of the anion may be greater at these points due to positive-roll bending not predicted by existing models. Consistent with this, the 5′ ends of these repeats are strikingly enriched at positions relative to the nucleosome dyad that bend towards the major groove, while their 3′ ends tend to sit outside these areas. Mutation rates are also higher at the 5′ ends of poly-dC:dG when CpG dinucleotides are excluded. These findings shed light on the mechanisms underlying bending/flexibility of the DNA double helix as well as the sequences that facilitate DNA packaging.
Structural basis of the inhibition of cystathionine γ‐lyase from Toxoplasma gondii by propargylglycine and cysteine

Cystathionine γ‐lyase (CGL) is a PLP‐dependent enzyme that catalyzes the last step of the reverse transsulfuration route for endogenous cysteine biosynthesis. The canonical CGL‐catalyzed process consists of an α,γ‐elimination reaction that breaks down cystathionine into cysteine, α‐ketobutyrate, and ammonia. In some species, the enzyme can alternatively use cysteine as a substrate, resulting in the production of hydrogen sulfide (H2S). Importantly, inhibition of the enzyme and consequently of its H2S production activity, makes multiresistant bacteria considerably more susceptible to antibiotics. Other organisms, such as Toxoplasma gondii, the causative agent of toxoplasmosis, encode a CGL enzyme (TgCGL) that almost exclusively catalyzes the canonical process, with only minor reactivity to cysteine. Interestingly, the substitution of N360 by a serine (the equivalent amino acid residue in the human enzyme) at the active site changes the specificity of TgCGL for the catalysis of cystathionine, resulting in an enzyme that can cleave both the CγS and the CβS bond of cystathionine. Based on these findings and to deepen the molecular basis underlying the enzyme‐substrate specificity, we have elucidated the crystal structures of native TgCGL and the variant TgCGL‐N360S from crystals grown in the presence of cystathionine, cysteine, and the inhibitor d,l‐propargylglycine (PPG). Our structures reveal the binding mode of each molecule within the catalytic cavity and help explain the inhibitory behavior of cysteine and PPG. A specific inhibitory mechanism of TgCGL by PPG is proposed.