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The inventory of the taxa collected in 2021 during the annual field trip of the Working Group for Floristics, Systematics, and Evolution of the Italian Botanical Society is reported. The field trip was held in the Mount Pennino massif, between Umbria and Marche administrative regions (central Italy). The flora documented for the study area amounts to 413 specific and subspecific taxa (including one hybrid), belonging to 234 genera and 64 families. Thirty-seven taxa are endemic to Italy; 42 are included in the IUCN Red List of the Italian Flora. Only three alien taxa were found. Ten taxa and one hybrid are considered floristic novelties because either new or confirmed for the regional flora of Umbria and/or Marche. Particularly, 6 taxa are new and 4 are confirmed for Umbria; one taxon and one hybrid are new for Marche.

The aim of this work was to develop a kinetic model based on the power law to describe the evolution of glycerol conversion and product distribution in the crude glycerol (G) acetylation reaction with acetic acid (AA) without the use of a catalyst. For this purpose, experimental tests were carried out with analytical glycerol under different reaction conditions (T = 80–160 °C, AA/G = 1–9 molar ratio, t = 0.25–2 h). The results showed the formation of mono- (MAG), di- (DAG) and tri- (TAG) acetylglycerols, liquid products with multiple applications in the chemical industry. From these results, a kinetic model based on the power law was implemented, which could acceptably estimate the experimental concentrations with an average relative error of 14.9%. Then, crude glycerol samples from different biodiesel industries were characterized by identifying and quantifying the impurities present in them (H2O, CH3OH, NaOH, NaCOOH, MONG and NaCl), and employed as reactants in the reaction tests. Given the significant differences observed in the glycerol conversion values compared to those obtained with analytical glycerol, further reaction tests were conducted to elucidate the effect of each impurity over the glycerol conversion. In these tests, the different impurities were added individually, maintaining the same concentration range as that of the crude glycerol samples. From the results obtained, global activity factors were introduced, which allowed us to modify the kinetic model to estimate glycerol conversions in the crude glycerol samples with an average relative error of 7%. It is hoped that this kinetic model will be a powerful tool useful for designing reactors on an industrial scale.

Abstract Isolated multiple port DC/DC converters, such as the Multiple Active Bridge (MAB) converter, have many recent applications, such as interconnection between grids, isolated uninterruptible power sources (UPSs) and electric vehicle chargers. MAB converter is an attractive solution from the point of view of the hardware because of its symmetry and its capability to be extended to any number of bridges with a moderate number of components. However, the main challenge of this converter is the control method in order to achieve independent control between the different ports and to minimize recirculating currents. For that reason, three‐port power converters have been already investigated, but many improvements can be done for a larger number of ports. This paper proposes to use a Fourier decomposition for the main power signals to separate their real and imaginary parts. As the signals work at the switching frequency, this decomposition is developed with analog electronics. Based on that, a general control method for regulating the power at the different ports is presented using the first harmonic component, which delivers most of the power. In this proposal, two nested control loops ensure accuracy for the DC power flow. Simulation and experimental results validate the proposal.

Abstract MYCN oncogene amplification is frequently observed in aggressive childhood neuroblastoma. Using an unbiased large-scale mutagenesis screen in neuroblastoma-prone transgenic mice, we identify a single germline point mutation in the transcriptional corepressor Runx1t1, which abolishes MYCN-driven tumorigenesis. This loss-of-function mutation disrupts a highly conserved zinc finger domain within Runx1t1. Deletion of one Runx1t1 allele in an independent Runx1t1 knockout mouse model is also sufficient to prevent MYCN-driven neuroblastoma development, and reverse ganglia hyperplasia, a known pre-requisite for tumorigenesis. Silencing RUNX1T1 in human neuroblastoma cells decreases colony formation in vitro, and inhibits tumor growth in vivo. Moreover, RUNX1T1 knockdown inhibits the viability of PAX3-FOXO1 fusion-driven rhabdomyosarcoma and MYC-driven small cell lung cancer cells. Despite the role of Runx1t1 in MYCN-driven tumorigenesis neither gene directly regulates the other. We show RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex recruited by HAND2 to enhancer regions to regulate chromatin accessibility and cell-fate pathway genes.

Objective: New echocardiographic definitions have been proposed for hemodynamic structural valve deterioration. We aimed to study their consistency in classifying structural valve deterioration after surgical aortic valve replacement. Methods: Data were used of patients undergoing surgical aortic valve replacement in a multicenter, prospective cohort study with a 5-year follow-up. All patients received the same stented bioprosthesis. Echocardiographic parameters were assessed by an independent core laboratory. Moderate or greater stenotic hemodynamic structural valve deterioration was defined according to Capodanno and colleagues, Dvir and colleagues, and the Valve Academic Research Consortium 3; regurgitation data were not considered in this analysis. Consistency was quantified on the basis of structural valve deterioration classification at subsequent time points. Results: A total of 1118 patients received implants. Patients’ mean age was 70 years, and 75% were male. Hemodynamic structural valve deterioration at any visit was present in 51 patients (4.6%), 32 patients (2.9%), and 34 patients (3.0%) according to Capodanno, Dvir, and Valve Academic Research Consortium 3. A total of 1064 patients (95%) were never labeled with structural valve deterioration by any definition. After the first classification with structural valve deterioration, 59%, 59%, and 65% had no subsequent structural valve deterioration classification according to Capodanno, Dvir, and Valve Academic Research Consortium 3, respectively. Conclusions: The current definitions of hemodynamic structural valve deterioration are strong negative predictors but inconsistent positive discriminators for the detection of stenotic hemodynamic structural valve deterioration. Although the diagnosis of structural valve deterioration may be categorical, echocardiographic indices lack this degree of precision in the first 5 years after surgical aortic valve replacement. The inconsistency of current structural valve deterioration definitions impedes the detection of true valve degeneration, which challenges the clinical usefulness of these definitions.

This article presents a new control strategy for a DC-DC boost converter used to supply a constant power load. The designed controller allows regulates the converter output voltage to a required reference value. By designing the controller based on the reduced order averaged model of the converter and using a nonlinear control technique based on feedback linearization, a simple-to-implement and stable controller for both operating modes of the converter (continuous and discontinuous conduction modes respectively) is obtained. The designed control strategy is validated through simulation and experimental results, demonstrating good dynamic performance and stability in both conduction modes, under variations in reference values and significant load changes. In addition, a comparison of the performance and implementation costs between the control strategy proposed in this paper and two strategies proposed by other authors is included.

Microbial communities in the world ocean are affected strongly by oceanic circulation, creating characteristic marine biomes. The high connectivity of most of the ocean makes it difficult to disentangle selective retention of colonizing genotypes (with traits suited to biome specific conditions) from evolutionary selection, which would act on founder genotypes over time. The Arctic Ocean is exceptional with limited exchange with other oceans and ice covered since the last ice age. To test whether Arctic microalgal lineages evolved apart from algae in the global ocean, we sequenced four lineages of microalgae isolated from Arctic waters and sea ice. Here we show convergent evolution and highlight geographically limited HGT as an ecological adaptive force in the form of PFAM complements and horizontal acquisition of key adaptive genes. Notably, ice-binding proteins were acquired and horizontally transferred among Arctic strains. A comparison with Tara Oceans metagenomes and metatranscriptomes confirmed mostly Arctic distributions of these IBPs. The phylogeny of Arctic-specific genes indicated that these events were independent of bacterial-sourced HGTs in Antarctic Southern Ocean microalgae.

Abstract The almost complete absence of regulations to protect invertebrates is a common condition in legal systems, including the European one, especially when it comes to invertebrates intended for human consumption. Thus, in the vast majority of cases, edible invertebrates do not receive even the most basic protection at slaughter. Despite recent research indicating that invertebrates are capable of feeling pain and stress, the humane step of stunning is not used on them. This is also the case for land snails, which are gastropod invertebrates whose consumption has now reached significant levels, already involving tonnes and that is expected to increase significantly as edible snail farming becomes more popular as a relatively low-cost, easy-to-perform, and sustainable alternative animal husbandry, thereby making land snails an increasingly economically important species. This paper presents and investigates a proposed stunning method based on the immersion of mollusks in CO2-supplemented and refrigerated water that could be used in the snail meat production chain to reduce the slaughter suffering of millions of these invertebrates. To this end, body condition descriptors (hemolymph parameters) in snails were determined before and after CO2 treatment in cold water, while generating useful data for defining a preliminary set of reference intervals for basal values.

Abstract Background Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. Methods We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. Results We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Conclusions Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

In November 1957, a significant milestone in the history of Opus Dei in the United States –which he had started in 1949–, marking the establishment of two distinct circumscriptions: the Chicago region and the Washington region. This article focuses on the formative years of the Washington region, spanning from 1957 to 1961, specifically highlighting the experiences of the male members of Opus Dei. It provides a chronological account, outlines the geographical and demographic aspects, and delves into certain institutional aspects, such as the organization’s relationship with the American hierarchy and its presence in Washington D.C., Boston and Cambridge, and New York.

Abstract Aspartate–glutamate carrier isoform 1 (AGC1) is a carrier responsible for the export of mitochondrial aspartate in exchange for cytosolic glutamate and is part of the malate–aspartate shuttle, essential for the balance of reducing equivalents in the cells. In the brain, mutations in SLC25A12 gene, encoding for AGC1, cause an ultra-rare genetic disease, reported as a neurodevelopmental encephalopathy, whose symptoms include global hypomyelination, arrested psychomotor development, hypotonia and seizures. Among the biological components most affected by AGC1 deficiency are oligodendrocytes, glial cells responsible for myelination processes, and their precursors [oligodendrocyte progenitor cells (OPCs)]. The AGC1 silencing in an in vitro model of OPCs was documented to cause defects of proliferation and differentiation, mediated by alterations of histone acetylation/deacetylation. Disrupting AGC1 activity could possibly reduce the availability of acetyl groups, leading to perturbation of many biological pathways, such as histone modifications and fatty acids formation for myelin production. Here, we explore the transcriptome of mouse OPCs partially silenced for AGC1, reporting results of canonical analyses (differential expression) and pathway enrichment analyses, which highlight a disruption in fatty acids synthesis from both a regulatory and enzymatic stand. We further investigate the cellular effects of AGC1 deficiency through the identification of most affected transcriptional networks and altered alternative splicing. Transcriptional data were integrated with differential metabolite abundance analysis, showing downregulation of several amino acids, including glutamine and aspartate. Taken together, our results provide a molecular foundation for the effects of AGC1 deficiency in OPCs, highlighting the molecular mechanisms affected and providing a list of actionable targets to mitigate the effects of this pathology.

Polydora hoplura is an invasive species and a harmful pest in commercial shellfish aquaculture, particularly for farmed abalone species. Different lines of treatment for Polydora affecting abalone have been explored, but with limited success. Using selective breeding to increase abalone resistance to and reduce shell damage from Polydora infestation could be a promising alternative. However, in abalone there is currently no information on the genetic variability for resistance to Polydora infestation. In the present study, heritability (h2) of traits associated with Pacific abalone resistance to P. hoplura were estimated after challenging abalone juveniles with trojan abalones heavily infested, using a nested experimental design, with 1 male crossed with 2–4 females. The heritability values were low but significant for some of those traits: survival h2=0.09; Infestation Intensity at Q50 h2 = 0.16 ± 0.11; and the proportion of the shell area occupied by blisters caused by the mud-worms h2 = 0.29 ± 0.14. These results suggest a significant potential for improving resistance or tolerance to P. hoplura infestation through selective breeding in Pacific abalone.

Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) is an ultra-rare autosomal recessive neurometabolic disorder caused by ALDH5A1 mutations presenting with autism and epilepsy. Here, we report the generation and characterization of human induced pluripotent stem cells (hiPSCs) derived from fibroblasts of three unrelated SSADHD patients – one female and two males with the CRISPR-corrected isogenic controls. These individuals are clinically diagnosed and are being followed in a longitudinal clinical study.

Background: Although various hemodynamic parameters to assess prosthetic performance are available, prosthesis–patient mismatch (PPM) is defined exclusively by effective orifice area (EOA) index thresholds. Adjusting for the Society of Thoracic Surgeons predicted risk of mortality (STS PROM), we aimed to explore the added value of postoperative hemodynamic parameters for the prediction of all-cause mortality at 5 years after aortic valve replacement. Methods: Data were obtained from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial, a multicenter prospective cohort study examining the performance of the Avalus bioprosthesis. Candidate predictors were assessed at the first follow-up visit; patients who had no echocardiography data, withdrew consent, or died before this visit were excluded. Candidate predictors included peak jet velocity, mean pressure gradient, EOA, predicted and measured EOA index, Doppler velocity index, indexed internal prosthesis orifice area, and categories for PPM. The performance of Cox models was investigated using the c-statistic and net reclassification improvement (NRI), among other tools. Results: A total of 1118 patients received the study valve, of whom 1022 were eligible for the present analysis. In univariable analysis, STS PROM was the sole significant predictor of all-cause mortality (hazard ratio, 1.40; 95% confidence interval, 1.26-1.55). When extending the STS PROM with single hemodynamic parameters, neither the c-statistics nor the NRIs demonstrated added prognostic value compared to a model with STS PROM alone. Similar findings were observed when multiple hemodynamic parameters were added. Conclusions: The STS PROM was found to be the main predictor of patient prognosis. The additional prognostic value of postoperative hemodynamic parameters for the prediction of all-cause mortality was limited.

In-depth research has been done in the literature on applying sophisticated modulation and control systems for power converters, such as Feedback Quantizer and Predictive Control. This research aims to enhance the Feedback Quantizer, a closed-loop modulation technique used in three-phase voltage source inverters. This method naturally reduces harmonics at low frequencies, which harms electrical machinery like transformers and AC motors. This modulation technique achieves an excellent follow-up of the fundamental voltage reference. One of the disadvantages of Feedback Quantizer are the low sampling time to achieve a good waveform quality; in addition, as it is not a carrier-based method, the switching frequency is variable, resulting in a dispersed harmonic spectrum. The three-phase voltage source inverter has eight valid states to monitor the voltage reference; the proposal consists of modifying the feedback quantizer modulation using virtual vectors by discrete space vectors, which achieves a better follow-up. The proposal considers a simplified implementation of discrete space vectors in such a way as to reduce the computational cost to obtain voltage and current waveforms with low WTHD, THD distortion, and a defined harmonic spectrum but with a high sampling time. The proposed modulation scheme obtains a THD of less than 2% in the load current, reducing the noise produced by the traditional scheme of Feedback Quantizer and using a fixed switching frequency for a sampling time of ( $200~\mu $ s). The above is an improvement compared to the conventional Feedback Quantizer. Additionally, it was possible to reduce the mathematical operations of the algorithm by a factor of 5.38 by using strategies to simplify the algorithm of the suggested scheme. The proposed technique operates correctly, according to experimental tests.INDEX TERMS Feedback quantizer, discrete space vector modulation, total harmonic distortion, weighted total harmonic distortion, voltage source converter, modulation scheme.

Objectives: A flow-gradient classification is used to determine the indication for intervention for patients with severe aortic stenosis (AS) with discordant echocardiographic parameters. We investigated the agreement in flow-gradient classification by stroke volume (SV) measurement at the left ventricular outflow tract (LVOT) and at the left ventricle. Methods: Data were used from a prospective cohort study and patients with severe AS (aortic valve area index ≤0.6 cm2/m2) with preserved ejection fraction (>50%) were selected. SV was determined by an echocardiographic core laboratory at the LVOT and by subtracting the 2-dimensional left ventricle end-systolic from the end-diastolic volume (volumetric). Patients were stratified into 4 groups based on SV index (35 mL/m2) and mean gradient (40 mm Hg). The group composition was compared and the agreement between the SV measurements was investigated using regression, correlation, and limits of agreement. In addition, a systematic LVOT diameter overestimation of 1 mm was simulated to study flow-gradient reclassification. Results: Of 1118 patients, 699 were eligible. The group composition changed considerably as agreement on flow state occurred in only 50% of the measurements. LVOT SV was on average 15.1 mL (95% limits of agreement −24.9:55.1 mL) greater than volumetric SV. When a systematic 1-mm LVOT diameter overestimation was introduced, the low-flow groups halved. Conclusions: There was poor agreement in the flow-gradient classification of severe AS as a result of large differences between LVOT and volumetric SV. Furthermore, this classification was sensitive to small measurement errors. These results stress that parameters beyond the flow-gradient classification should be considered to ensure accurate recommendations for intervention.