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Method-of-moments (MoMs) is coupled with partial element equivalent circuit (PEEC) to compute Joule and hysteresis losses in the armor, shields, and moisture barriers (MBs) of a submarine tripolar cable. The large size and complex structure of the linear algebraic system resulting from the problem discretization demands for a suitably tailored solver. We describe a block–Gauß–Seidel preconditioner for Krylov subspace methods that allows for a matrix-free solver implementation, resulting in a dramatic reduction of computation time and memory requirements with respect to other brute-force modeling approaches.

IMPORTANCE: Current third-line therapies for patients with metastatic colorectal cancer (MCRC) have limited efficacy. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors for RAS wild-type (WT) MCRC may be valuable for these patients. OBJECTIVE: To compare the anti-EGFR monoclonal antibody panitumumab plus standard-of-care trifluridine-tipiracil with trifluridine-tipiracil alone as third-line therapy for RAS WT MCRC. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 randomized clinical trial (RCT) was conducted in 7 Italian centers from June 2019 to April 2022. Patients with refractory RAS WT MCRC who had a partial or complete response to first-line chemotherapy plus an anti-EGFR monoclonal antibody and an anti-EGFR drug–free interval of 4 or more months during second-line therapy were included. INTERVENTIONS: Patients were randomized 1:1 to receive panitumumab plus trifluridine-tipiracil or trifluridine-tipiracil alone. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS). Circulating tumor DNA (ctDNA) extended sequence variation analysis was performed in a subgroup of patients. RESULTS: Of 62 included patients, 31 received panitumumab plus trifluridine-tipiracil (19 [61.3%] male; median age, 65 years [range, 39-81 years]) and 31 received trifluridine-tipiracil alone (17 [54.8%] male; median age, 66 years [range, 32-82 years]). The primary end point was met. Median PFS was 4.0 months (95% CI, 2.8-5.3 months) in the panitumumab plus trifluridine-tipiracil arm vs 2.5 months (95% CI, 1.4-3.6 months) in the trifluridine-tipiracil only (hazard ratio [HR], 0.48; 95% CI, 0.28-0.82; P = .007). Pretreatment plasma RAS/BRAF WT ctDNA identified patients obtaining prolonged clinical benefit with panitumumab plus trifluridine-tipiracil compared with trifluridine-tipiracil, with PFS rates at 6 months of 38.5% vs 13.0% and at 12 months of 15.4% vs 0%. A ctDNA liquid-biopsy extended mutation analysis by FoundationOne Liquid CDx (profiling 324 genes) was performed in a subgroup of patients with baseline plasma RAS/BRAF WT ctDNA; in 15 of 23 patients (65.2%) whose tumors were WT for KRAS, NRAS, BRAFV600E, EGFR, ERBB2, MAP2K1, and PIK3CA, median PFS was 6.4 months (95% CI, 3.7-9.2 months). Within this group of 15 patients, 2 (13.3%) had partial response, 11 (73.3%) had stable disease, and 2 (13.3%) had disease progression as best response. CONCLUSIONS AND RELEVANCE: In this RCT, third-line treatment with the anti-EGFR monoclonal antibody panitumumab plus the standard-of-care trifluridine-tipiracil resulted in improved PFS compared with treatment with trifluridine-tipiracil alone among patients with refractory RAS WT MCRC. The findings support the clinical utility of liquid biopsy–guided anti-EGFR rechallenge therapy for refractory RAS WT MCRC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05468892

Our study delves into the evolving landscape of Agrivoltaics (APV) diffusion in Italy, where this innovative application of photovoltaics encounters multifaceted challenges. Through an analysis of press reports and experts' interviews, we aim to elucidate the Social Representations of APV, considering the nuanced perspectives of both expert and non-expert stakeholders. Within these viewpoints, a complex interplay emerges, marked by four major themes: ambiguity, justice, (agronomic) risk, and exploitation. By analysing the representational processes behind the construction of each theme, we posit the need for a more comprehensive understanding of sustainability in the context of APV diffusion, highlighting the importance of clear definitions and guidelines within regulations and policies.

The introduction of quantum concepts is increasingly making its way into generative machine learning models. However, while there are various implementations of quantum generative adversarial networks, the integration of quantum elements into diffusion models remains an open and challenging task. In this work, we propose a potential version of a quantum diffusion model that leverages the established idea of classical latent diffusion models. This involves using a traditional autoencoder to reduce images, followed by operations with variational circuits in the latent space. To effectively assess the benefits brought by quantum computing, the images generated by the quantum latent diffusion model have been compared to those generated by a classical model with a similar number of parameters, evaluated in terms of quantitative metrics. The results demonstrate an advantage in using a quantum version, as evidenced by obtaining better metrics for the images generated by the quantum version compared to those obtained by the classical version. Furthermore, quantum models continue to outperform even when considering small percentages of the dataset for training, demonstrating the quantum’s ability to extract features more effectively even in a few shot learning scenario.

In the architectural heritage field, a complete and in-depth knowledge of the assets is indispensable for any restoration and conservation strategy. In this context, the Historical Building Information Modelling (HBIM) technique is gaining much interest in supporting the diagnostic phase and the design and management of conservation activities. The HBIM provides opportunities to collect, organize and integrate information coming from different sources, inspections, and diagnosis techniques as well as to use standardized and effective tools for orienting cultural heritage asset management. This study addresses the challenges of developing HBIM for large-scale assets, that require adapting the conventional workflow to deliver results in a reasonable time. To this aim, a novel procedure involving a fit-for-purpose Inventory form and a scan-to-BIM approach is proposed. The data acquisition process is speeded up using multiple surveying techniques, and the modelling and information phases benefit from the interoperability among different tools that are already known by professionals in the field. As such, the main innovation lies in the ability to oversee the entire process through a single software, ensuring centralized and efficient control. This innovative process has been applied to investigate a significant portion of the city walls of Pisa, proving its ability to support the decision-making phase for planned conservation of large-scale architectural heritage. The emphasis is on the all-encompassing, interdisciplinary understanding of the assets across different scales. The suggested approach ensures a swift yet precise and reliable outcome in the diagnostic process and facilitating the critical temporal assessments and the review of information by any actor involved in the conservation.

We present a two-dimensional semi-conservative variant of the depth-averaged material point method (DAMPM) for modeling flow-like landslides. The mathematical model is given by the shallow water equations, derived from the depth-integration of the Navier–Stokes equations with the inclusion of an appropriate bed friction model and material rheology, namely Voellmy and the depth-integrated Bingham viscoplastic stress model, respectively. After assessing the accuracy and performance of the proposed numerical method by means of several idealized benchmarks, we test its behavior in a realistic scenario. • The method accurately reproduces realistic landslides and mudflow run-out. • The method can be effectively applied to real scenarios with complex bed topologies. • A well-balanced DAMPM formulation is presented and tested on different topographies. • The method ensures the conservation of mass and momenta between particles and nodes. [ABSTRACT FROM AUTHOR]

It is known that if Gis a group such that the centre factor group G/ζ(G)is polycyclic, then also the commutator subgroup G′is polycyclic. The aim of this paper is to describe this situation from a lattice point of view. It is proved that if Gis a group admitting a permodularly embedded non-periodic subgroup Psuch that the interval [G/P] is a polycyclic lattice, then Gcontains a polycyclic normal subgroup Nsuch that G/Nis quasihamiltonian.

In comprehensive lipidomics studies, accurate quantification is essential but biological and/or clinical relevance is often hindered due to unwanted variations such as lipid degradation during sample preparation, matrix effects and non-linear responses of analytical instruments. In addition, the wide chemical diversity of lipids can complicate the accurate identification of individual lipids. These analytical limitations can potentially be corrected efficiently by the use of lipid-specific isotopically labelled internal standards (IS) but currently such IS mixtures have limited coverage of the mammalian lipidome. In this study, an in vivo13C labelling strategy was employed to explore four species (Escherichia coli, Arthrospira platensis, Saccharomyces cerevisiaeand Pichia pastoris) as a source of 13C-labelled internal standards (13C-ISs) for more accurate and quantitative liquid chromatography (LC)-mass spectrometry (MS)-based lipidomics. Results showed that extracts from 13C-labelled P. pastorisand S. cerevisiaecontain the highest percentage of uniformly labelled lipids (both 83% compared to 67% and 69% in A. platensisand E. coli, respectively) and 13C-labelled P. pastorisextract was identified as the optimum source of 13C-ISs for comprehensive data normalisation to correct unwanted variations during sample preparation and LC-MS analysis. Overall, use of a biologically generated 13C-IS lipid mixture of 357 identified lipid ions resulted in significant reduction in the lipid CV% of normalisation compared with other normalisation methods using total ion counts or a commercially available deuterated internal standard mixture. This improved normalisation using 13C-IS was confirmed in a typical lipidomics analysis using a large number of samples (>100+) and long analysis time (>70 h). This study highlights the benefit of an in vivolabelling strategy for reducing technical and analytical variations introduced during sample preparation and analysis in lipidomics studies.

Lithium-ion batteries are widely used in electric vehicles due to their high specific energy value. The continuous charge/discharge cycles pf batteries, determining a change of their State of Health (SoH) and a reduction of their Remaining Useful Life (RUL). The relevant literature describes a variety of methods for the prognostic of battery degradation and RUL estimation, based on electrochemical models or on statistical and artificial intelligence techniques. However, the capacity degradation of lithium-ion batteries depends on many uncertain parameters that are suitable to be estimated and modeled within a probabilistic framework. Therefore, the development of new probabilistic methodologies for the prognostic of lithium-ion batteries can be useful and effective. In this paper, probabilistic models based on time series (AutoRegressive Integrated Moving Average model with eXogenous predictors, (ARIMAX)) and regression approaches (Linear Quantile Regression (LQR), Bootstrap Multiple Linear Regression (B-MLR) and Bayesian Bootstrap Multiple Linear Regression (BB-MLR)) are developed and compared for this purpose. All the considered models are specifically suited up to exploit data coming from Accelerated Degradation Tests (ADTs), and developed under two different approaches (i.e., non-differentiation and differentiation of the target time series) to predict SoH and RUL. Moreover, a dedicated procedure to extract a single, point value from the probabilistic predictions is presented to let the models work also in deterministic scenarios. The performance and the comparison between the proposals and several benchmarks taken from the literature are carried out using data from publicly available databases, confirming the validity and the accuracy of the proposed solutions.

This article proposes a circuital model that describes polarization and depolarization currents (PDCs) observed in thin samples of polymeric materials under the application of an average electric field up to 30 kV/mm. The model employs the least possible number of parameters to fit the experimental measurements. A single carrier with a negative charge is considered. The polarization curves are modeled by a power law to account for transport assisted by shallow traps. A model for the deep traps with a Gaussian distribution of the density of states (DOS) describes the depolarization curves. Experimental measurements made on various materials with different charging and discharging times suggest that a portion of the deep traps is filled within a few seconds, while the time needed to release the trapped charges is in the order of several hours. The agreement between experimental and simulated currents confirms the validity of the proposed model that can be seen as a generalization of the extended Debye model.

ABSTRACTRecent restoration work on Pisa Cathedral provided the opportunity for a multidisciplinary analysis of the monument that identified interesting aspects of its history, preservation, and structural safety. In particular, the study of the matroneumprovided clues about the role of the structures in the well-known fire that occurred in 1595. Alteration patterns and damage forms on the stone masonry walls were analysed to better understand their relationship with this catastrophic event. The investigation of the stone specimens enabled textural and mineralogical features typical of fire damage to be identified on the surface. The evidence of fire also provided a terminus ante quemto correctly interpret and diachronically date a damage pattern consisting of cracks in the eastern arch supporting the dome. The cracks were likely to have been induced by a soil consolidation phenomenon related to the renowned leaning of the Pisa tower, centuries before the fire.

ABSTRACTData communication networks have large importance for the immediate post-earthquake emergency management and community resilience. In this study, the framework of simulation-based probabilistic seismic risk analysis of data communication infrastructure is applied to the real case of the inter-university data network of the Campania region (southern Italy). The network is constituted by point-like facilities (racks located within buildings and containing the device routing and managing traffic) and distributed links (buried fiber optic cables). The seismological, geological, and geotechnical features of the region were characterized together with the seismic vulnerability of each element of the network. The network performance is quantified in terms of traffic loss before and after the seismic event. Results are provided in terms of annual rate of events exceeding traffic loss thresholds and allow to identify the portion of the network mostly contributing to the seismic performance.

A study to investigate the relationship between the occurrences of uterine dehiscence in term pregnant scarred uteri and the presence of altered biochemical behavior of the scarring process was conducted. The results revealed that uterine dehiscence of scarred uterus may be related to altered biochemical behavior of the scarring process.

Research has been conducted on collagen content and platelet-derived growth factor and on tissue growth factor expression in the uterine lower segment's myometrium from a woman with type IA osteogenesis imperfecta. Results demonstrate the minimum collagen amount from osteogenesis imperfecta, and suggest myoterial biochemical modifications and the recurrent uterine rupture.

Research has been conducted on insulin-like growth factor type I receptor expression in uterine leiomyomas. The authors have demonstrated that the shrinkage in uterine volume after gonadotropin-releasing hormone analog administration is due to the reduction in insulin-like growth factor type I receptor levels.

Purpose: To describe a case of fulminant idiopathic intracranial hypertension (IIH) in a child with “malignant” presentation.Case report: A 16-year-old, previously healthy, girl presented with bilateral visual loss and bilateral global limitation of eye movements in the absence of headache. Extensive laboratory evaluation for infectious, inflammatory, autoimmune, and neoplastic conditions was negative. Magnetic resonance imaging (MRI) of the brain and lumbar puncture findings were consistent with a diagnosis of IIH. Extraocular motility improved in the next few days as well as optic disc edema but visual acuity remained poor.Conclusion: The authors believe that the acute, severe, and fulminant (“malignant”) presentation with markedly elevated intracranial pressure may produce the unique presentation of severe vision loss and bilateral complete ophthalmoplegia. Interestingly, there was no headache. To our knowledge this is the first such case to be reported in the English language ophthalmic literature.

AbstractThis paper continues the investigation of the structure of uncountable groups whose large subgroups are normal. Moreover, we describe the behaviour of uncountable groups in which every large subgroup is close to normal with the only obstruction of a finite section.

Euphorbia myrsinites is one of the oldest spurges described and used in folk medicine. It is characterized by blue-grey stems similar to myrtle, and it is spread in the Mediterranean region, Asia, and the USA. Chemical analysis of E. myrsinites collected in Turkey afforded the isolation of 4 diterpenes based on the so-called myrsinane skeleton being tetraesters of the tetracyclic diterpene alcohol myrsinol. In this study, the phytochemical analysis of this species collected in Italy has been undertaken to afford the isolation of a new atisane diterpene, named myrsatisane, 3 ingenol derivatives, along with the 4 tetraester derivatives previously found. A triterpene compound based on the euphane skeleton has also been isolated. Structural elucidation of the new myrsatisane was based on spectroscopic techniques, including HR-MS and 1- and 2-dimensional NMR experiments. Its relative configuration was determined by NOE correlations, while absolute stereochemistry was obtained by quantum-mechanical DFT studies. While diterpenes with the atisane skeleton are relatively common in Euphorbia species, this is the first report of an atisane diterpene from E. myrsinites. All the isolated terpenes were tested for anti-inflammatory activity on J774A.1 macrophages stimulated with lipopolysaccharide by evaluation of nitrite and pro-inflammatory cytokine Il-1 β levels. Among tested compounds, the 3 ingenol diterpenes exhibited a dose-dependent (0.001 – 3 µM) significant activity, thus showing their potential as anti-inflammatory drug candidates. [ABSTRACT FROM AUTHOR]

Euphorbia myrsinites is one of the oldest spurges described and used in folk medicine. It is characterized by blue-grey stems similar to myrtle, and it is spread in the Mediterranean region, Asia, and the USA. Chemical analysis of E. myrsinites collected in Turkey afforded the isolation of 4 diterpenes based on the so-called myrsinane skeleton being tetraesters of the tetracyclic diterpene alcohol myrsinol. In this study, the phytochemical analysis of this species collected in Italy has been undertaken to afford the isolation of a new atisane diterpene, named myrsatisane, 3 ingenol derivatives, along with the 4 tetraester derivatives previously found. A triterpene compound based on the euphane skeleton has also been isolated. Structural elucidation of the new myrsatisane was based on spectroscopic techniques, including HR-MS and 1- and 2-dimensional NMR experiments. Its relative configuration was determined by NOE correlations, while absolute stereochemistry was obtained by quantum-mechanical DFT studies. While diterpenes with the atisane skeleton are relatively common in Euphorbia species, this is the first report of an atisane diterpene from E. myrsinites. All the isolated terpenes were tested for anti-inflammatory activity on J774A.1 macrophages stimulated with lipopolysaccharide by evaluation of nitrite and pro-inflammatory cytokine Il-1 β levels. Among tested compounds, the 3 ingenol diterpenes exhibited a dose-dependent (0.001 – 3 µM) significant activity, thus showing their potential as anti-inflammatory drug candidates. [ABSTRACT FROM AUTHOR]

Euphorbia myrsinites is one of the oldest spurges described and used in folk medicine. It is characterized by blue-grey stems similar to myrtle, and it is spread in the Mediterranean region, Asia, and the USA. Chemical analysis of E. myrsinites collected in Turkey afforded the isolation of 4 diterpenes based on the so-called myrsinane skeleton being tetraesters of the tetracyclic diterpene alcohol myrsinol. In this study, the phytochemical analysis of this species collected in Italy has been undertaken to afford the isolation of a new atisane diterpene, named myrsatisane, 3 ingenol derivatives, along with the 4 tetraester derivatives previously found. A triterpene compound based on the euphane skeleton has also been isolated. Structural elucidation of the new myrsatisane was based on spectroscopic techniques, including HR-MS and 1- and 2-dimensional NMR experiments. Its relative configuration was determined by NOE correlations, while absolute stereochemistry was obtained by quantum-mechanical DFT studies. While diterpenes with the atisane skeleton are relatively common in Euphorbia species, this is the first report of an atisane diterpene from E. myrsinites. All the isolated terpenes were tested for anti-inflammatory activity on J774A.1 macrophages stimulated with lipopolysaccharide by evaluation of nitrite and pro-inflammatory cytokine Il-1 β levels. Among tested compounds, the 3 ingenol diterpenes exhibited a dose-dependent (0.001 – 3 µM) significant activity, thus showing their potential as anti-inflammatory drug candidates. [ABSTRACT FROM AUTHOR]

•Yolk sac tumor (YST) is a rare cancer that affects young people. Symptoms include visual problems, seizures, and paralysis. Treatment options include surgery, chemotherapy (CT), and radiation therapy (RT).•A man with seminoma and liver metastases had seizures and was found to have a lesion on the left frontal lobe. The tumor was removed through craniotomy surgery and identified as a pure-YST. Adjuvant RT and CT led to remission and the patient is symptom-free after two years.•Tumors were commonly found in the pineal region, cerebral lobes, and sellar region. Male and female patients had different overall survival but not among different tumor locations. There was no significant difference in overall survival between the two histological subtypes.•The study found that complete tumor resection along with radiation and chemotherapy is the best option for managing brain tumors. Females have a better prognosis. The patients were followed for an average of 28 months, with a median overall survival of 13 months.

This paper presents a radio-frequency power amplifier (RF PA) with load impedance sensing circuitry incorporated into its output matching network (OMN), but without insertion of series elements into the RF transmission path, limiting its impact on performance. The approach is based on multi-port reflectometry, such as can be used in sampled-line impedance sensors, generalized to an arbitrary linear network and applied to the existing OMN of a PA. With the addition of samplers to the OMN, offline computation is performed to determine the complex reflection coefficient at a specified reference plane. The proof-of-concept class-AB harmonically-tuned sampled-OMN PA operating at 3 GHz demonstrates load reflection coefficient sensing within less than 4.6% error over the entire measured region of the Smith chart, i.e. up to 0.8 magnitude reflection coefficient, when the PA is driven with a 6-dBm CW signal. For a 2-tone input with 5-MHz tone spacing and 6-dBm average input power, sensing accuracy is within 16.3% for 80% of the measured loads. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text.Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer’s disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer’s disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity. Metal-protein attenuating compounds represent a class of agents proposed for Alzheimer’s disease treatment, as they reduce abnormal interactions of metal ions with Aβ, inhibit Aβ oligomerization and prevent deleterious redox reactions in the brain. The present work investigates the protective action of an isoniazid-derived aroylhydrazone, INHHQ, on AβO-induced memory impairment. Systemic administration of a single dose of INHHQ (1 mg/kg) prevented both short-term and long-term memory impairment caused by AβOs in mice. In-vitro studies showed that INHHQ prevents Cu(Aβ)-catalyzed production of reactive oxygen species. Although the mechanism of protection by INHHQ is not yet fully understood at a molecular level, the results reported herein certainly point to the value of aroylhydrazones as promising neuroprotective agents in Alzheimer’s disease and related disorders.

Purpose: Worldwide, natural hazards are affecting urban cultural heritage and World Heritage Sites, exacerbating other environmental and human-induced threats deriving from deterioration, uncontrolled urbanization and unsustainable tourism. This paper aims to develop a disaster risk analysis in Italian historic centers because they are complex large-scale systems that are cultural and economic resources for the country, as well as fragile areas. Design/methodology/approach: A heritage-oriented qualitative methodology for risk assessment is proposed based upon the formalization of risk as a function of hazard, vulnerability and exposure, taking into account the values of cultural heritage assets. Findings: This work provides a contribution to the body of knowledge in the Italian context of disaster risk mitigation on World Heritage Sites, opening for further research on the monitoring and maintenance of the tangible heritage assets. The application to the site of San Gimignano proves the effectiveness of the methodology for proposing preventive measures and actions that ensure the preservation of cultural values and a safer built environment. Originality/value: The application of a value-based simplified approach to risk analysis is a novelty for historic centers that are listed as World Heritage Sites.

Background: In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12.5g per day) is still unknown. Objective: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset. Methods: To collect the scientific evidences regarding this topic the keywords “light alcohol drinking”, “light alcohol consumption” and “cancer”, were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded. Results: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed. Conclusion: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.

ABSTRACTThe identification of the mechanisms predisposing to stroke may improve its preventive and therapeutic strategies in patients with essential hypertension. The role of macroautophagy/autophagy in the development of hypertension-related stroke needs to be clarified. We hypothesized that a defective autophagy may favor hypertension-related spontaneous stroke by promoting mitochondrial dysfunction. We studied autophagy in the stroke-prone spontaneously hypertensive (SHRSP) rat, which represents a clinically relevant model of stroke associated with high blood pressure. We assessed autophagy, mitophagy and NAD+:NADH levels in brains of SHRSP and stroke-resistant SHR fed with high salt diet. Vascular smooth muscle cells silenced for the mitochondrial complex I subunit Ndufc2gene (NADH:ubiquinone oxidoreductase subunit C2) and cerebral endothelial cells isolated from SHRSP were also used to assess autophagy/mitophagy and mitochondrial function in response to high salt levels. We found a reduction of autophagy in brains of high salt-fed SHRSP. Autophagy impairment was associated with NDUFC2 downregulation, mitochondrial dysfunction and NAD+depletion. Restoration of NAD+levels by nicotinamide administration reactivated autophagy and reduced stroke development in SHRSP. A selective reactivation of autophagy/mitophagy by Tat-Beclin 1 also reduced stroke occurrence, restored autophagy/mitophagy and improved mitochondrial function. Endothelial progenitor cells (EPCs) from subjects homozygous for the thymine allele variant at NDUFC2/rs11237379, which is associated with NDUFC2deficiency and increased stroke risk, displayed an impairment of autophagy and increased senescence in response to high salt levels. EPC senescence was rescued by Tat-Beclin 1. Pharmacological activation of autophagy may represent a novel therapeutic strategy to reduce stroke occurrence in hypertension.Abbreviations10 VSMCs: aortic vascular smooth muscle cells; COX4I1/COX IV: cytochrome c oxidase subunit 4I1; ECs: endothelial cells; EPCs: endothelial progenitor cells; JD: Japanese-style diet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NAD: nicotinamide adenine dinucleotide; NDUFC2: NADH:ubiquinone oxidoreductase subunit C2; NMN: nicotinamide mononucleotide; RD: regular diet; SHRSP: stroke-prone spontaneously hypertensive rat; SHRSR: stroke-resistant spontaneously hypertensive rat.

Fetal exposure to certain phthalate esters can disrupt testis development in rodents and lead to male reproductive disorders, but with a causal link less certain in humans. Di(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates found in the environment and in rodents it is known to induce serious testis toxicity, as well as male reproductive disorders including cryptorchidism, hypospadias, impaired spermatogenesis and reduced fertility. In this study, we show that perinatal DEHP exposure disrupts gap junction localization in fetal and postnatal rat testis and correlate these findings to morphological changes. The protein Connexin 43 (CX43), normally expressed strongly in testicular gap junctions, was markedly downregulated in Leydig cells of DEHP-exposed fetal testes. In the postnatal testes, CX43 expression was recovered in the DEHP-exposed animals, even though Leydig cell clusters and malformed cords with intratubular Leydig cells were still present.

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Textiles are one of the major sources of microplastic pollution to aquatic environments and have also been reported in dry and wet atmospheric deposition. There is still a lack of information on the direct release of microfibers from garments to the air and on the influence of textile characteristics including structure, type of yarn, and twist. The present study examines microfiber emissions directly to the air and to water as a consequence of laundering. Polyester garments with different textile characteristics were examined including various material compositions, fabric structure, yarn twist, fiber type, and hairiness. Scaling up our data indicates release of microfibers per person per year to the air is of a similar order of magnitude to that released to wastewater by laundering. The lowest releases to both air and water were recorded for a garment with a very compact woven structure and highly twisted yarns made of continuous filaments, compared with those with a looser structure (knitted, short staple fibers, lower twist). Our results demonstrate for the first time that direct release of microfibers from garments to air as a consequence of wear is of equal importance to releases to water. Currently there is considerable interest in interventions focused on capture from wastewater. However, our results suggest more effective interventions are likely to result from changes in textile design that could reduce emissions to both air and water.

Combinatorially generated molecular repertoires have been largely used to identify novel bioactive compounds. Ever more sophisticated technological solutions have been proposed to simplify and speed up such process, expanding the chemical diversity space and increasing the prospect to select new molecular entities with specific and potent activities against targets of therapeutic relevance. In this context, random mixtures of oligomeric peptides were originally used and since 25 years they represent a continuous source of bioactive molecules with potencies ranging from the sub-nM to microM concentration. Synthetic peptide libraries are still employed as starting “synthetic broths” of structurally and chemically diversified molecular fragments from which lead compounds can be extracted and further modified. Thousands of studies have been reported describing the application of combinatorial mixtures of synthetic peptides with different complexity and engrafted on diverse structural scaffolds for the identification of new compounds which have been further developed and also tested in in vivo models of relevant diseases. We briefly review some of the most used methodologies for library preparation and screening and the most recent case studies appeared in the literature where compounds have reached at least in vivo testing in animal or similar models. Recent technological advancements in biotechnology, engineering and computer science have suggested new options to facilitate the discovery of new bioactive peptides. In this instance, we anticipate here a new approach for the design of simple but focused tripeptide libraries against druggable cavities of therapeutic targets and its complementation with existing approaches.

In recent years, the Building Information Modeling (BIM) methodology has emerged as a pivotal approach for the design and management optimization of infrastructures. The need for fully integrated models has led to develop various tools to support the designers throughout the decision-making process of the entire life cycle of an infrastructure project. In particular, the design of transport infrastructures is a complex process that involves issues concerning all the different fields of civil engineering. In this framework, the BIM method can be efficiently applied to support the project of drainage systems capable of protecting railways and roadways from potential hydraulic risks. According to the above, this study presents an optimized BIM-based methodology for the integrated analysis of the flood risk and the design of the drainage system components. Specifically, the proposed method allows to implement hydraulics and hydrological numerical models as part of the different design phases. Such an approach holds two main advantages for the designer. On one hand, the computational modelling provides a decisive support in both defining water surface profiles over the designed area and identifying the spots exposed to major hydrological risks. On the other hand, the hydraulically guided modelling of each component of the drainage system allows for an increase of the overall productivity and efficiency of the project. A case study is presented to highlight the great potential of the proposed approach in ensuring both the integrity of datasets and the rapid clash detection of critical interferences between each system component. In conclusion, new perspectives about a fully integrated hydraulics analysis in the infrastructures design process are stressed out.

Analyzing harmful constituents in e-cigarette aerosols typically involves adopting a methodology used for analyzing tobacco smoke. Cambridge filter pads (CFP) are the basis of numerous protocols for analyzing the various classes of compounds representing 93 harmful and potentially harmful constituents identified in tobacco smoke by the FDA. This paper describes a simplified method for trapping the low volatility components of e-cigarette aerosols using a single trapping procedure followed by physical extraction. The trap is a plug of amorphous silica fibers (0.75 g of 4 μm diameter) within a 10 mL syringe inserted between the e-cigarette mouthpiece and the pump of the vaping machine. The method is evaluated for emissions from three generations of e-cigarette device (Kangertech CE4, EVOD, and Subox Mini-C). On average, the silica wool traps about 94% of the vaporized liquid mass in the three devices and higher levels of condensate is retained before reaching saturation compared with CFP. The condensate is then physically extracted from the silica wool plug using a centrifuge. Condensate is then available for use directly in multiple analytical procedures or toxicological experiments. The method is tested by comparison with published analyses of carbonyls, among the most potent toxicants and carcinogens in e-cigarette emissions. Ranges for HPLC-DAD analyses of carbonyl-DNPH derivatives in a laboratory formulation of e-liquid are formaldehyde (0.182 ± 0.023 to 9.896 ± 0.709 μg puff–1), acetaldehyde (0.059 ± 0.005 to 0.791 ± 0.073 μg puff–1), and propionaldehyde (0.008 ± 0.0001 to 0.033 ± 0.023 μg puff–1); other carbonyls are identified and quantified. Carbonyl concentrations are also consistent with published experiments showing marked increases with variable power settings (10W to 50W). Compared with CFPs, e-cigarette aerosol collection by silica wool requires only one vaping session for multiple analyte groups, traps more condensate per puff, and collects more condensate before saturation.

Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the ‘angio-lymphokine’ PlGF, in turn, specifically induced the differentiation of pathogenic TH17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.

The paper presents an interactive electronic guide application prototype able to recommend personalized multiple-day tourist itineraries to mobile web users. The proposed application relies on an evolutionary optimizer that allows the determination, in an acceptable time, of a near-optimal user-adapted tour for each day of the visit by considering different conflicting objectives. The tour optimizer automatically plans the itinerary by selecting the sights of potential interest based on user preferences, the available visit time considered on a daily basis, opening days and hours, visiting times, accessibility of the places of interest and weather forecasting. The interactive functionalities and facilities provided by the application are illustrated along with the model used to adapt the tourist itinerary to user preferences and constraints. An experimental qualitative and quantitative evaluation has been performed to assess the validity of the guide prototype. Particular attention has been devoted to the usability of the application and its graphic unit interface along with user satisfaction.

Abstract Problems involving large-scale global optimization (LSGO) are becoming more and more frequent. For this reason, the last few years have seen an increasing number of researchers interested in improving optimization metaheuristics in such a way as to cope effectively with high-dimensional search domains. Among the techniques to enhance scalability, one of the most studied is Cooperative Coevolution (CC), an effective divide-and-conquer strategy for decomposing a large-scale problem into lower-dimensional subcomponents. However, despite the progress made in the LSGO field, one of such optimizations can still require a very high number of objective function evaluations. Therefore, when the evaluation of a candidate solution requires complex calculations, LSGO can become a challenging task. Nonetheless, to date few studies have investigated the application of optimization metaheuristics to objective functions that are simultaneously high-dimensional and computationally significant. To address such a research issue, this article investigates a surrogate-assisted CC (SACC) optimizer, in which fitness surrogates are exploited within the low-dimensional subcomponents resulting from the problem decomposition. The SACC algorithm is investigated on a rich test-bed composed of 1000-dimensional problems. According to the results, SACC is able to significantly boost the convergence of the CC optimizer, leading in many cases to a relevant computational gain. [ABSTRACT FROM AUTHOR]

Biobased plastics are sometimes promoted as “environmentally friendly” compared to their conventional petrochemical-based counterparts, but their ecotoxicity is only partially understood. Biobased fibers are widely used in clothing and wet wipes and can accumulate in soils through the application of biosolid fertilizers. This study examined the lethal thresholds and sublethal toxicity of chemically characterized, additive-free, biobased (viscose and lyocell) compared to petrochemical-based (polyester) fibers on the key ecosystem engineer, Esenia fetida. Viscose and lyocell had LC20values of 14.00 and 22.66 mg·L–1, respectively, and no observed effect concentrations (NOEC) of 0–2.8 mg·L–1(72 h, OECD TG207 filter paper method), while for polyester these were LC2015.6–31.3 mg·L–1and NOEC 0–15.6 mg·L–1. Following 28 days of exposure to soils (OECD TG222) contaminated with environmentally relevant concentrations (100 mg kg–1), viscose significantly reduced the mass of progeny compared to polyester. Earthworms exposed to lyocell had a marginal growth reduction (−18%; compared to −11% to −13% in other treatments) linked to increased bioturbation activity. The biobased fibers examined here have greater acute toxicity at high concentrations and broadly similar sublethal effects on E. fetidacompared to polyester. Our study highlights the importance of detailed testing before advocating specific materials as plastic alternatives/substitutes to conventional plastics.

•The SERPINA1 gene encodes Alpha-1-Antitrypsin (A1AT), a protease inhibitor.•SERPINA1 gene polymorphisms are associated with ANCA-associated vasculitis.•Their presence represents poor prognostic factors in ANCA-associated vasculitis.

The high toughness and work to fracture of hierarchical composites, like antler bone, involve structural mechanisms at the molecular, nano-, and micro scales, which are not completely explored. A key characteristic of the high energy absorption of such materials is the large hysteresis during cyclic loading, but its origin remains unknown. In situ synchrotron X-ray diffraction tests during tensile loading of antler bone showed heterogeneous fibrillar deformation and hysteresis. To explain the origin of these mechanisms from the nanostructure of antler bone, here we develop a class of finite-element fibril models whose predictions are compared to experimental data across a range of potential composite architectures. We demonstrate that the key structural motif enabling a match to experimental data is an axially staggered arrangement of stiff mineralized collagen fibrils coupled with weak, damageable interfibrillar interfaces.

Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers.

Attentional bias toward infant faces is associated with parental sensitivity and supports the infant-caregiver attachment relationship, ultimately fostering child health outcomes. However, experience-related determinants of parents' attentional bias to infant faces have been poorly investigated. We examined attentional bias to infant versus adult faces in a sample of same-sex mothers (N = 76), and whether it varied depending on maternal involvement in childcare and the perceived quality of past experiences of care.

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.

If $k$is a positive integer, a group $G$is said to have the $FE_{k}$-property if for each element $g$of $G$there exists a normal subgroup of finite index $X(g)$such that the subgroup $\langle g,x\rangle$is nilpotent of class at most $k$for all $x\in X(g)$. Thus, $FE_{1}$-groups are precisely those groups with finite conjugacy classes ($FC$-groups) and the aim of this paper is to extend properties of $FC$-groups to the case of groups with the $FE_{k}$-property for $k>1$. The class of $FE_{k}$-groups contains the relevant subclass $FE_{k}^{\ast }$, consisting of all groups $G$for which to every element $g$there corresponds a normal subgroup of finite index $Y(g)$such that $\langle g,U\rangle$is nilpotent of class at most $k$, whenever $U$is a nilpotent subgroup of class at most $k$of $Y(g)$.

The lack of a complete understanding of the complex reciprocal interactions between hydrological processes and the structure and function of microbial communities limits our ability to improve the predictions of microbial metabolism in streams. We report here on how overlying water velocity and losing and gaining flux interact with bacterial community structure and its activity to control oxygen consumption in a sandy streambed under high nutrient levels. We used an experimental flume packed with natural sediment and measured the bacterial biomass distribution and oxygen profiles in the streambed and across bed forms. Local oxygen consumption rates were calculated with a 1‐D numerical model (GRADIENT). Bacterial abundance and production rates varied across the bed form within 1 order of magnitude, while their taxonomic classes were similar across bed forms despite variations in flow conditions and sediment disturbance events. However, bacterial production rates were not directly correlated with bacterial abundance. On the other hand, oxygen consumption rates ranged over 4 orders of magnitude across the bed forms and were highly correlated with the vertical exchange flux between the water and the streambed. The results strongly suggest that under high nutrient levels, the system is, in general, transport limited and that predicting oxygen consumption rates depends on local vertical exchange fluxes. Biomass distributions varied within 1 order of magnitude across the bed forms and were not strongly correlated with oxygen consumption ratesOxygen consumption rates varied over 4 orders of magnitude and were dependent on the vertical exchange flux at the water‐streambed interfaceMain bacterial taxonomic classes were similar across bed forms despite variations in flow conditions and sediment disturbance events