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Functional alterations in irritable bowel syndrome have been associated with defects in bioenergetics and the mitochondrial network. Effects of high fat, adequate-protein, low carbohydrate ketogenic diet (KD) involve oxidative stress, inflammation, mitochondrial function, and biogenesis. The aim was to evaluate the KD efficacy in reducing the effects of stress on gut mitochondria. Newborn Wistar rats were exposed to maternal deprivation to induce IBS in adulthood. Intestinal inflammation (COX-2 and TRL-4), cellular redox status (SOD 1, SOD 2, PrxIII, mtDNA oxidatively modified purines), mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, mtDNA content), and autophagy (Beclin-1, LC3 II) were evaluated in the colon of exposed rats fed with KD (IBD-KD) or standard diet (IBS-Std), and in unexposed controls (Ctrl). IBS-Std rats showed dysfunctional mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, and mtDNA contents lower than in Ctrl) associated with inflammation and increased oxidative stress (higher levels of COX-2 and TLR-4, SOD 1, SOD 2, PrxIII, and oxidatively modified purines than in Ctrl). Loss of autophagy efficacy appeared from reduced levels of Beclin-1 and LC3 II. Feeding of animals with KD elicited compensatory mechanisms able to reduce inflammation, oxidative stress, restore mitochondrial function, and baseline autophagy, possibly via the upregulation of the PPAR-γ/PGC-1α axis.

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotypes remain unknown. Here we have measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We found that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in wound repair and in skin cancer growth. Sphingolipid composition defined fibroblast subpopulations while sphingolipid metabolic rewiring drove cell state transitions. These data uncover a role for cell-to-cell lipid heterogeneity in the determination of cell states and reveal a new regulatory component to the homeostasis and self-organization of multicellular systems.

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.

UVscope is an instrument, based on a multi-pixel photon detector, developed to support experimental activities for high-energy astrophysics and cosmic ray research. The instrument, working in single photon counting mode, is designed to directly measure light flux in the wavelengths range 300-650~nm. The instrument can be used in a wide field of applications where the knowledge of the nocturnal environmental luminosity is required. Currently, one UVscope instrument is allocated onto the external structure of the ASTRI-Horn Cherenkov telescope devoted to the gamma-ray astronomy at very high energies. Being co-aligned with the ASTRI-Horn camera axis, UVscope can measure the diffuse emission of the night sky background simultaneously with the ASTRI-Horn camera, without any interference with the main telescope data taking procedures. UVscope is properly calibrated and it is used as an independent reference instrument for test and diagnostic of the novel ASTRI-Horn telescope., Comment: Published (Open Access) in "Experimental Astronomy"

Main factors change the international freight transport alimenting (and being alimented by) the increasing of globalization. In this scenario, the role of ports also changes. The single port cannot compete in the new global economic scenario. The port system arises from the alliance, or merge, of several ports to optimize the resources of the individual ports. The paper is articulated into two main parts. The first one presents the main theoretical approaches to explain how ports could respond to the new requirements imposed by gigantism, carriers’ alliances and land-sea integration. The second one presents a critical analysis of some representative case studies of cooperation among ports, in order to aggregate the observed processes in some macro-classes. The work may be considered a first step of a research, able to open several directions to study the competition and cooperation process among ports with Transport System Models (TSMs). The use of TSMs could allow to extend the consolidated quantitative methods developed in the field of passengers’ mobility and freight distribution on terrestrial transport networks to the field of maritime transport and ports.

HERMES-TP/SP (High Energy Rapid Modular Ensemble of Satellites Technologic and Scientific Pathfinder) is a constellation of six 3U nano-satellites hosting simple but innovative X-ray detectors, characterized by a large energy band and excellent temporal resolution, and thus optimized for the monitoring of Cosmic High Energy transients such as Gamma Ray Bursts and the electromagnetic counterparts of Gravitational Wave Events, and for the determination of their positions. The projects are funded by the Italian Ministry of University and Research and by the Italian Space Agency, and by the European Union Horizon 2020 Research and Innovation Program under Grant Agreement No. 821896. HERMES-TP/SP is an in-orbit demonstration, that should be tested starting from 2022. It is intrinsically a modular experiment that can be naturally expanded to provide a global, sensitive all sky monitor for high-energy transients., Comment: 15 pages, 3 figures, Proceedings of SPIE Astronomical Telescopes and Instrumentation 2020

Background & Aims Understanding factors responsible for the increased bleeding tendency in acute‐on‐chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding. Methods Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin‐modified thrombin generation (TG) and thromboelastometry (ROTEM®). In study part 1 (case‐control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed. Results Ninety‐one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not. Conclusion We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel—the MYC pathway and the cyclin D–cyclin-dependent kinase (CDK)–retinoblastoma protein (RB) pathway1,2. Both MYC and the cyclin D–CDK–RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1–cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis. AMBRA1-mediated degradation of cyclin D through CRL4–DDB1 regulates cell proliferation and prevents replication stress in neurodevelopment and cancer.

Noninvasive biomarkers are required for addressing crucial clinical needs. The ideal biomarker should be easily accessible and provide a unique characteristic for a healthy status or a pathological condition. In the last years, microRNAs (miRNAs) have been proposed as promising tissue-based biomarkers for several diseases such as cancer and cardiovascular diseases. Recently, miRNAs have shown great potential as novel noninvasive biomarkers, due to their high stability in human body fluids such as serum, plasma, and urine. Furthermore, many other noncoding RNAs (ncRNAs) such as long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have shown to be novel biomarkers as well. The aim of this exciting research field is to offer novel tools, allowing translational scientists to develop new strategies for diagnosis, screening, and monitoring of diseases. In this book chapter, the miRandola database and its applications will be introduced. The database offers the possibility to explore information on ncRNAs as noninvasive biomarkers, manually extracted from scientific literature and public available resources.

Recent results of Hassett, Kuznetsov and others pointed out countably many divisors \( \mathcal{C}_{d} \) in the open subset of \( \mathbb{P}^{55}= \mathbb{P}(\textit{H}^{o}(\mathcal{O}_{\mathbb{P}^{5}}(3))) \) parametrizing all cubic 4-folds and lead to the conjecture that the cubics corresponding to these divisors should be precisely the rational ones. Rationality has been proved by Fano for the first divisor \( \mathcal{C}_{14} \), in [RS19a] for the divisors \( \mathcal{C}_{26} \) and \( \mathcal{C}_{38} \), and in [RS19b] for \( \mathcal{C}_{42} \). In this note we describe explicit birational maps from a general cubic fourfold in \( \mathcal{C}_{14} \), in \( \mathcal{C}_{26} \) and in \( \mathcal{C}_{38} \) to P4, providing concrete geometric realizations of the more abstract constructions in [RS19a] and of the theoretical framework developed in [RS19b]. We also exhibit an explicit relationship between the divisor C14 and a certain divisor in the open subset of \( \mathbb{P}^{39}= \mathbb{P}(\textit{H}^{o}(\mathcal{O}_{Y}(2))) \) parametrizing smooth quadratic sections of a del Pezzo fivefold \( \textit{Y}=\mathbb{G}(1,4)\cap\mathbb{P}^{8}\subset\mathbb{P}^{8} \), the so-called Gushel–Mukai fourfolds.

Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy’s decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

We address our interest to the development of a theory of viscosity solutions a la Crandall-Lions for path-dependent partial differential equations (PDEs), namely PDEs in the space of continuous paths C([0, T ]; R^d). Path-dependent PDEs can play a central role in the study of certain classes of optimal control problems, as for instance optimal control problems with delay. Typically, they do not admit a smooth solution satisfying the corresponding HJB equation in a classical sense, it is therefore natural to search for a weaker notion of solution. While other notions of generalized solution have been proposed in the literature, the extension of the Crandall-Lions framework to the path-dependent setting is still an open problem. The question of uniqueness of the solutions, which is the more delicate issue, will be based on early ideas from the theory of viscosity solutions and a suitable variant of Ekeland's variational principle. This latter is based on the construction of a smooth gauge-type function, where smooth is meant in the horizontal/vertical (rather than Frechet) sense. In order to make the presentation more readable, we address the path-dependent heat equation, which in particular simplifies the smoothing of its natural "candidate" solution. Finally, concerning the existence part, we provide a new proof of the functional Ito formula under general assumptions, extending earlier results in the literature.

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.

The HERMES-TP/SP (High Energy Rapid Modular Ensemble of Satellites -- Technologic and Scientific Pathfinder) is an in-orbit demonstration of the so-called distributed astronomy concept. Conceived as a mini-constellation of six 3U nano-satellites hosting a new miniaturized detector, HERMES-TP/SP aims at the detection and accurate localisation of bright high-energy transients such as Gamma-Ray Bursts. The large energy band, the excellent temporal resolution and the wide field of view that characterize the detectors of the constellation represent the key features for the next generation high-energy all-sky monitor with good localisation capabilities that will play a pivotal role in the future of Multi-messenger Astronomy. In this work, we will describe in detail the temporal techniques that allow the localisation of bright transient events taking advantage of their almost simultaneous observation by spatially spaced detectors. Moreover, we will quantitatively discuss the all-sky monitor capabilities of the HERMES Pathfinder as well as its achievable accuracies on the localisation of the detected Gamma-Ray Bursts., 19 pages, 13 figures, Proceedings of SPIE Astronomical Telescopes and Instrumentation 2020

Background: Based on data from the Ministry of Health, which highlighted the earlier onset of Covid-19 epidemic in Italy, compared with the Europe, we would like to present a statistical elaboration on the impact of measures taken by the Government, during the phase 1 and the start of phase 2. Methods: After the implementation of a Bayesian changepoint detection method, we looked for a best fit model, based on the first part of time series data, in order to observe the progress of the data in the presence and absence of the restriction measures introduced. Results: Both the implementation of changepoint detection method and the analysis of the curves showed that the decree that marked the start of lockdown has had the effect of slowing down the epidemic by allowing thestart of a plateau between 21 and 25 March. Moreover, the decree that decided the beginning of phase 2 on 4 May did not have a negative impact. Conclusion: This statistical analysis supports the hypothesis that stringent measures decreased hospitalization, thanks to a slowing down in the evolution of the epidemic compared with what was expected.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017&ndash, 2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.

In this paper, the development procedure of an innovative control algorithm is shown, with the aim of improving handling performance of a high-end sport vehicle by actively controlling aerodynamic forces acting on the vehicle itself. The proposed control algorithm operates indirectly by modifying ride-heights of the vehicle through an active suspensions system. The vehicle dynamics analysis is conducted in parallel to the aerodynamics analysis performed in a concurrent engineering operation. The software used for control algorithms development is VI-CarRealTime, in co-simulation with Matlab-Simulink, with an extended use of the MaxPerformance package. Specific tracks have been implemented ad hoc to highlight the effects of the control systems operation in development phase. To better explore the potential of the technique, a fuzzy logic system was developed.

Objectives Serum biomarkers have suboptimal accuracy for the early diagnosis of bacterial infection (BI) in cirrhosis. The aim of the study was to evaluate the diagnostic and prognostic accuracy of presepsin (PSP) in a cohort of hospitalized patients with cirrhosis. Methods All adult cirrhotics admitted between 03.2016 and 06.2019 were consecutively evaluated. PSP was measured using chemiluminescent enzyme immunoassay, and its accuracy was compared with that of common biomarkers. Results A total of 278 cirrhotic patients for a total of 448 hospitalizations were prospectively collected. Prevalence of BI at admission was 28.3%. Median (range) Log10PSP in the whole cohort was 2.83 (2.48–3.19) ng/L, significantly higher in patients with BI than in patients without (p10PSP showed sensitivity, specificity and AUC-ROC of 0.66 (95% CI 0.57–0.74), 0.63 (95% CI 0.57–0.68) and 0.69 (95% CI 0.63–0.73), lower than that of C-reactive protein (p=0.002), but similar to procalcitonin (p=0.18) Patients with BI at hospitalization had higher probability of 28-day mortality (sub-hazard ratio [sHR] 2.65;95% CI 1.49–4.70; p=0.001). At multivariate Cox’s regression analysis, Log10PSP (sHR 2.4; 95% CI 1.22–4.82; p=0.01) together with age and severity of liver disease, was an independent predictor of short-term mortality. Conclusions PSP shows low diagnostic accuracy for BI in cirrhosis, but it is an independent predictor of short-term mortality. PSP may be a biomarker of systemic inflammation, commonly seen in end-stage liver disease.

Background Studies on tumor-secreted microRNAs point to a functional role of these in cellular communication and reprogramming of the tumor microenvironment. Uptake of tumor-secreted microRNAs by neighboring cells may result in the silencing of mRNA targets and, in turn, modulation of the transcriptome. Studying miRNAs externalized from tumors could improve cancer patient diagnosis and disease monitoring and help to pinpoint which miRNA-gene interactions are central for tumor properties such as invasiveness and metastasis. Methods Using a bioinformatics approach, we analyzed the profiles of secreted tumor and normal interstitial fluid (IF) microRNAs, from women with breast cancer (BC). We carried out differential abundance analysis (DAA), to obtain miRNAs, which were enriched or depleted in IFs, from patients with different clinical traits. Subsequently, miRNA family enrichment analysis was performed to assess whether any families were over-represented in the specific sets. We identified dysregulated genes in tumor tissues from the same cohort of patients and constructed weighted gene co-expression networks, to extract sets of co-expressed genes and co-abundant miRNAs. Lastly, we integrated miRNAs and mRNAs to obtain interaction networks and supported our findings using prediction tools and cancer gene databases. Results Network analysis showed co-expressed genes and miRNA regulators, associated with tumor lymphocyte infiltration. All of the genes were involved in immune system processes, and many had previously been associated with cancer immunity. A subset of these, BTLA, CXCL13, IL7R, LAMP3, and LTB, was linked to the presence of tertiary lymphoid structures and high endothelial venules within tumors. Co-abundant tumor interstitial fluid miRNAs within this network, including miR-146a and miR-494, were annotated as negative regulators of immune-stimulatory responses. One co-expression network encompassed differences between BC subtypes. Genes differentially co-expressed between luminal B and triple-negative breast cancer (TNBC) were connected with sphingolipid metabolism and predicted to be co-regulated by miR-23a. Co-expressed genes and TIF miRNAs associated with tumor grade were BTRC, CHST1, miR-10a/b, miR-107, miR-301a, and miR-454. Conclusion Integration of IF miRNAs and mRNAs unveiled networks associated with patient clinicopathological traits, and underlined molecular mechanisms, specific to BC sub-groups. Our results highlight the benefits of an integrative approach to biomarker discovery, placing secreted miRNAs within a biological context.

The paper deals with economic effects due to city logistics implementations. An analysis framework is proposed and the results of a survey, consisting of interviews with experts in city logistics, are presented. The survey was carried out to point out the level of benefits or costs expected by city logistics measure implementation. The results show that city users are expected to receive more benefits from environment-friendly vehicle measures, while transport and logistics operators can averagely obtain considerable benefits from demand management and public&ndash, private collaboration solutions.

This paper investigates two existence theorems for the path-dependent heat equation, which is the Kolmogorov equation related to the window Brownian motion, considered as a C ⁢ ( [ - T , 0 ] ) {C([-T,0])} -valued process. We concentrate on two general existence results of its classical solutions related to different classes of terminal conditions: the first one is given by a cylindrical not necessarily smooth random variable, the second one is a smooth generic functional.

In this paper we focus on the so called identification problem for a backward SDE driven by a continuous local martingale and a possibly non quasi-left-continuous random measure. Supposing that a solution (Y, Z, U) of a backward SDE is such that $Y(t) = v(t, X(t))$ where X is an underlying process and v is a deterministic function, solving the identification problem consists in determining Z and U in term of v. We study the over-mentioned identification problem under various sets of assumptions and we provide a family of examples including the case when X is a non-semimartingale jump process solution of an SDE with singular coefficients., arXiv admin note: text overlap with arXiv:1512.06234

Modeling of masonry confinement has been usually derived from concrete confinement, which was deeply tested in the last decades. However concrete and masonry have some crucial differences, e.g., ordinary concrete performance can be usually fully defined by the cylindrical compressive strength, while masonry does not. In the present work, a failure criterion is considered on a solid mechanics base. Such criteria are useful not only to introduce non-uniform stress states, as those developed in non-axisymmetric confined elements, but also to be implemented in FEM. The validity of the adopted failure criterion has been checked against actively confined clay brick masonry and a database of passive confinement tests available in the scientific literature.

HERMES (High Energy Rapid Modular Ensemble of Satellites) Technological and Scientific pathfinder is a space borne mission based on a LEO constellation of nano-satellites. The 3U CubeSat buses host new miniaturized detectors to probe the temporal emission of bright high-energy transients such as Gamma-Ray Bursts (GRBs). Fast transient localization, in a field of view of several steradians and with arcmin-level accuracy, is gained by comparing time delays among the same event detection epochs occurred on at least 3 nano-satellites. With a launch date in 2022, HERMES transient monitoring represents a keystone capability to complement the next generation of gravitational wave experiments. In this paper we will illustrate the HERMES payload design, highlighting the technical solutions adopted to allow a wide-energy-band and sensitive X-ray and gamma-ray detector to be accommodated in a CubeSat 1U volume together with its complete control electronics and data handling system., Comment: 12 pages, 13 figures. Proceedings of SPIE "Astronomical Telescopes and Instrumentation" 2020

The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.

miR-28-5p is downregulated in some tumor tissues in which it has been demonstrated to have tumor suppressor (TS) activity. Here, we demonstrate that miR-28-5p acts as a TS in prostate cancer (PCa) cells affecting cell proliferation/survival, as well as migration and invasion. Using the miRNA pull out assay and next generation sequencing, we collected the complete repertoire of miR-28-5p targets, obtaining a data set (miR-28-5p targetome) of 191 mRNAs. Filtering the targetome with TargetScan 7, PITA and RNA22, we found that 61% of the transcripts had miR-28-5p binding sites. To assign a functional value to the captured transcripts, we grouped the miR-28-5p targets into gene families with annotated function and showed that six transcripts belong to the transcription factor category. Among them we selected SREBF2, a gene with an important role in PCa. We validated miR-28-5p/SREBF2 interaction, demonstrating that SREBF2 inhibition affects almost all the tumor processes altered by miR-28-5p re-expression, suggesting that SREBF2 is an important mediator of miR-28-5p TS activity. Our findings support the identification of the targetome of cancer-related miRNAs as a tool to discover genes and pathways fundamental for tumor development, and potential new targets for anti-tumor therapy.

In this paper, we investigate BSDEs where the driver contains a distributional term (in the sense of generalised functions) and derive general Feynman–Kac formulae related to these BSDEs. We introduce an integral operator to give sense to the equation and then we show the existence of a strong solution employing results on a related PDE. Due to the irregularity of the driver, the $Y$-component of a couple $(Y,Z)$ solving the BSDE is not necessarily a semimartingale but a weak Dirichlet process.

Background Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(−)] increased s-IP according to normal or altered La/Ma ratio. Methods The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann–Whitney or the Kruskal–Wallis with Dunn’s post-test was used to assess differences among the groups. Results As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(−) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(−) ones. Conclusions The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population. Trial registration NCT01574209. Registered March 2012. First recruitment started in April 2012.

In this paper, we present a discrete-type approximation scheme to solve continuous-time optimal stopping problems based on fully non-Markovian continuous processes adapted to the Brownian motion filtration. The approximations satisfy suitable variational inequalities which allow us to construct $\epsilon$-optimal stopping times and optimal values in full generality. Explicit rates of convergence are presented for optimal values based on reward functionals of path-dependent SDEs driven by fractional Brownian motion. In particular, the methodology allows us to design concrete Monte-Carlo schemes for non-Markovian optimal stopping time problems as demonstrated in the companion paper by Bezerra, Ohashi and Russo., Comment: Final version to appear in Journal of Applied Probability

The well-known age-related mitochondrial dysfunction deeply affects heart because of the tissue's large dependence on mitochondrial ATP provision. Our study revealed in aged rat heart a significant 25% decrease in mtDNA relative content, a significant 29% increase in the 4.8 Kb mtDNA deletion relative content, and a significant inverse correlation between such contents as well as a significant 38% decrease in TFAM protein amount. The TFAM-binding activity to specific mtDNA regions increased at those encompassing the mtDNA replication origins, D-loop and Ori-L. The same mtDNA regions were screened for different kinds of oxidative damage, namely Single Strand Breaks (SSBs), Double Strand Breaks (DSBs), abasic sites (AP sites) and oxidized bases as 7,8-dihydro-8-oxoguanine (8oxoG). A marked increase in the relative content of mtDNA strand damage (SSBs, DSBs and AP sites) was found in the D-loop and Ori-L regions in the aged animals, unveiling for the first time in vivo an age-related, non-stochastic accumulation of oxidative lesions in these two regions that appear as hot spots of mtDNA damage. The use of Formamidopyrimidine glycosylase (Fpg) demonstrated also a significant age-related accumulation of oxidized purines particularly in the D-loop and Ori-L regions. The detected increased binding of TFAM to the mtDNA damage hot spots in aged heart suggests a link between TFAM binding to mtDNA and loss of mitochondrial genome likely through hindrance of repair processes.

Aim To assess the diagnostic accuracy of a new fecal test for detecting Helicobacter pylori (H. pylori), using13C-urea breath test as the reference standard, and explore bacterial antibiotic resistance. Methods We conducted a prospective two-center diagnostic test accuracy study. We enrolled consecutive people≥ 18 years without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent 13C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for a new fecal investigation (THD fecal test). The detection of bacterial 23S rRNA subunit gene indicated H. pylori infection. We also used the index diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed index test and reference test standard results blinded to the other test findings. We estimated sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, diagnostic accuracy, positive and negative likelihood ratio (LR), together with 95% confidence intervals (CI). Results We enrolled 294 consecutive participants (age: Median 37.0 years, IQR: 29.0-46.0 years; men: 39.8%). Ninety-five (32.3%) participants had a positive13C-urea breath test. Twenty-three (7.8%) participants underwent upper endoscopy with histology, with a full concordance between 13C-urea breath test and histology in detecting H. pylori infection. Four (1.4%) out of the 294 participants withdrew from the study after the enrollment visit and did not undergo THD fecal testing. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2% (CI: 84.2%-96.3%), specificity 98.5% (CI:96.8%-100%), PPV 96.5% (CI: 92.6%-100%), NPV 95.6% (CI: 92.8%-98.4%), accuracy 95.9% (CI: 93.6%-98.2%), positive LR 59.5(CI: 19.3-183.4), negative LR 0.10 (CI: 0.05-0.18). Out of 83 infected participants identified with the THD fecal test, 34 (41.0%) had bacterial genotypic changes consistent with antibiotic-resistant H. pylori infection. Of these, 27 (32.5%) had bacterial strains resistant to clarithromycin, 3 (3.6%) to levofloxacin, and 4 (4.8%) to both antibiotics. Conclusion The THD fecal test has high performance for the non-invasive diagnosis of H. pylori infection while additionally enabling the assessment of bacterial antibiotic resistances.

Dysbiosis may contribute to constipation and its symptoms, therefore probiotic administration could improve significantly gut health and functions. The aim of the study was to investigate the effects of a long-lasting administration of Lactobacillus reuteri DSM 17938 (LR DSM 17938) on symptoms and quality of life (QoL) score in patients with functional constipation (FC). 56 FC patients with normal colonic transit time and without anorectal disorders and pelvic floor dysfunctions completed the study. LR DSM 17938 was administered for 105 days in a randomised double-blind clinical trial (28 patients per arm). Individual and cumulative scores including the Constipaq, a modified Constipation Scoring System (CSS) that considers the patient assessment of constipation-QoL (PAC-QoL), were calculated during the preliminary visit (V0), at day 15 (end of the induction period with a LR DSM 17938 double dosage, 4×108 cfu), day 60 (intermediate evaluation) and day 105 (V4) after a standard dosage (2×108 cfu). At the end of treatment, the beneficial effect of LR DSM 17938 compared to placebo was significantly evident for symptoms related to gas content and dysbiosis (abdominal discomfort, pain and bloating), incomplete defecation and helps for defecation (P

In this paper we correct a mistake in [C. Ciliberto, F. Russo, On surfaces with two apparent double points. Adv. Geom. 5 (2005), 223–235].

We establish the existence of smooth densities for solutions to a broad class of path-dependent SDEs under a Hormander-type condition. The classical scheme based on the reduced Malliavin matrix turns out to be unavailable in the path-dependent context. We approach the problem by lifting the given n-dimensional path-dependent SDE into a suitable L p -type Banach space in such a way that the lifted Banach-space-valued equation becomes a state-dependent reformulation of the original SDE. We then formulate Hormander's bracket condition in R n for non-anticipative SDE coefficients defining the Lie brackets in terms of vertical derivatives in the sense of the functional Ito calculus. Our pathway to the main result engages an interplay between the analysis of SDEs in Banach spaces, Malliavin calculus, and rough path techniques.

A new concept of building is represented by Zero Energy Buildings (ZEBs). This paper evaluates the possibility to obtain a NZEB (for office building) by using only “on-site” renewable energy, solely on the roof. A dynamic energy simulation code, EnergyPlus, is used. Two different Italian climatic zones (Palermo and Naples) and two typologies of building are considered: square or rectangular basis. For the building with square basis, the energy self-sufficiency is kept up to a higher number of the building levels (8 for Naples, 10 for Palermo) compared to the case of rectangular basis (7 levels for Naples, 9 for Palermo).