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Purpose: Osteochondritis dissecans (OCD) can lead to detrimental effects in the affected joints. Osteochondral autologous transplantation (OAT) allows to restore the articular surface with an autologous osteochondral unit. While short-term results are documented, there is a lack of long-term data. Aim of this study was to analyze the long-term clinical results of single-plug OAT for the treatment of knee OCD. Methods: Twenty patients (14 men, 6 women) were treated with single plug-OAT. Mean age was 23.6 ± 9.9 years and BMI was 23.3 ± 3.6 kg/m2. Lesion size was 2.3 ± 1.6 cm2 and defects included 14 medial femoral condyles (MFC) and 6 lateral femoral condyles (LFC). Patients were followed up prospectively at baseline, 24 months, 60 months, and at minimum ten years (12.6 ± 2.0 years) using the IKDC subjective score and through an overall judgment on treatment satisfaction. The activity level was evaluated with the Tegner score and adverse events and failures were also recorded. Factors influencing the clinical outcomes, including age, sex, BMI, lesions size, and lesion location were also investigated. Results: No severe adverse events and no surgical failures were reported and 85.0% of patients were satisfied at a minimum ten year follow-up. Subjective IKDC showed a significant and stable improvement at all follow-ups, passing from 45.3 ± 16.5 at baseline to 73.7 ± 16.6 at 24 months (p < 0.0005), to 72.9 ± 16.6 at 60 months (p < 0.0005), and to 74.1 ± 20.8 at long-term follow-up (p < 0.0005). Patients with OCD lesions localized on the LFC obtained lower results compared to those with MFC lesions at two years and five years (p = 0.034 and p = 0.023). The highest long-term scores were obtained in patients with lesion size lower than 2 cm2 (89.1 ± 8.8) compared to patients with lesion size between 2 and 4 cm2 (69.2 ± 15.7), and patients with lesion size larger than 4 cm2 (63.8 ± 34.6). Conclusions: OAT is a suitable technique to treat knee OCD in young patients and offers a high patient satisfaction and a significant improvement in terms of clinical subjective scores, with results remaining stable over time, although without reaching the pre-injury activity level. No severe adverse events and no surgical failures have been documented confirming OAT as a valid treatment option, although the best long-term results for lesions smaller than 2 cm2 and for MFC lesions should be considered when choosing this procedure to address knee OCD lesions. Highlights: Single-plug OAT for knee OCD provided good clinical outcome over time with no failures. Despite the good symptoms and functional improvement, a limited activity level was recovered. The lesion size remains a concern for single-plug OAT, with better results with smaller lesions. Lesion site can influence the final outcome offered by this technique, with better results for MFC. [ABSTRACT FROM AUTHOR]

Polymers are versatile materials widely used in various industries, with significant applications in biomedicine where biofouling on polymer surfaces presents major health and economic challenges. Biofouling, initiated by bacterial adhesion, can be mitigated by modifying surface properties through laser micro- and nano-texturing, an approach that offers advantages over chemical treatments. This study introduces an economical mass production process for textured polymeric components using injection molding to replicate hierarchical textures. Testing revealed that all textured samples significantly reduced bacterial adhesion compared to untextured surfaces across different designs and bacteria types after 24 h of culture. The study examined factors like wettability, nanoscale roughness, and pattern dimensions to explain these outcomes, comparing them with existing studies. Despite all textured samples showing decreased wettability and roughness, these factors alone did not ensure reduced bacterial adhesion. The most effective anti-adhesive performance was observed in surfaces with parallel ridge patterns, which segmented the surface into isolated areas that limited bacterial interaction and hindered micro-colony formation, highlighting the importance of specific surface patterning in combating biofouling. [ABSTRACT FROM AUTHOR]

Context. The light element (anti-)correlations shown by globular clusters (GCs) are the main spectroscopic signature of multiple stellar populations. These internal abundance variations provide us with fundamental constraints on the formation mechanism of stellar clusters. Aims. Using Gaia-ESO, the largest and most homogeneous survey of open clusters (OCs), we intend to check whether these stellar aggregates display the same patterns. Based on previous studies of many GCs, several young and massive clusters in the Magellanic Clouds, as well as a few OCs, we do not expect to find any anti-correlation, given the low mass of Milky Way OCs. Methods. We used the results based on UVES spectra of stars in Gaia-ESO to derive the distribution of Na and O abundances and see whether they show an unexplained dispersion or whether they are anti-correlated. By selecting only high-probability members with high-precision stellar parameters, we ended up with more than 700 stars in 74 OCs. We examined the O-Na distribution in 28 OCs with at least 4 stars available as well as the Na distribution in 24 OCs, with at least 10 stars available. Results. We find that the distribution of Na abundances is compatible with a single-value population, within the errors. The few apparent exceptions can be explained by differences in the evolutionary phase (main sequence and giant post first dredge-up episode) or by difficulties in analysing low gravity giants. We did not find any indication of an Na-O anti-correlation in any of the clusters for which O has been derived. Conclusions. Based on the very small spread we find, OCs maintain the status of single stellar populations. However, a definitive answer requires studying more elements and larger samples covering different evolutionary phases. This will be possible with the next generation of large surveys. [ABSTRACT FROM AUTHOR]

In this review, a pedagogical introduction to the concepts of slow-roll inflationary universe and number of e-folds is provided. In particular, the differences between the basic notion of number of e-folds ( N e ), total number of e-folds ( N T ) and number of e-folds before the end of inflation (N) are outlined. The proper application of the number of e-folds before the end of inflation is discussed both as a time-like variable for the scalar field evolution and as a key parameter for computing inflationary predictions. [ABSTRACT FROM AUTHOR]

Stellar mergers and accretion events have been crucial in shaping the evolution of the Milky Way (MW). These events have been dynamically identified and chemically characterized using red giants and main-sequence stars. RR Lyrae (RRL) variables can play a crucial role in tracing the early formation of the MW since they are ubiquitous, old (t ≥ 10 Gyr) low-mass stars and accurate distance indicators. We exploited Data Release 3 of the GALAH survey to identify 78 field RRLs suitable for chemical analysis. Using synthetic spectra calculations, we determined atmospheric parameters and abundances of Fe, Mg, Ca, Y, and Ba. Most of our stars exhibit halo-like chemical compositions, with an iron peak around [Fe/H] ≈ −1.40, and enhanced Ca and Mg content. Notably, we discovered a metal-rich tail, with [Fe/H] values ranging from −1 to approximately solar metallicity. This sub-group includes almost 1/4 of the sample, it is characterized by thin disc kinematics and displays sub-solar α-element abundances, marginally consistent with the majority of the MW stars. Surprisingly, they differ distinctly from typical MW disc stars in terms of the s-process elements Y and Ba. We took advantage of similar data available in the literature and built a total sample of 535 field RRLs for which we estimated kinematical and dynamical properties. We found that metal-rich RRLs (1/3 of the sample) likely represent an old component of the MW thin disc. We also detected RRLs with retrograde orbits and provided preliminary associations with the Gaia–Sausage–Enceladus, Helmi, Sequoia, Sagittarius, and Thamnos stellar streams. [ABSTRACT FROM AUTHOR]

Quantum computing has rapidly gained prominence for its unprecedented computational efficiency in solving specific problems when compared to classical computing counterparts. This surge in attention is particularly pronounced in the realm of quantum machine learning (QML) following a classical trend. Here we start with a comprehensive overview of the current state-of-the-art in Quantum Support Vector Machines (QSVMs). Subsequently, we analyze the limitations inherent in both annealing and gate-based techniques. To address these identified weaknesses, we propose a novel hybrid methodology that integrates aspects of both techniques, thereby mitigating several individual drawbacks while keeping the advantages. We provide a detailed presentation of the two components of our hybrid models, accompanied by the presentation of experimental results that corroborate the efficacy of the proposed architecture. These results pave the way for a more integrated paradigm in quantum machine learning and quantum computing at large, transcending traditional compartmentalization. [ABSTRACT FROM AUTHOR]

We study a class of early universe cosmological models based on Einstein–Cartan gravity and including a higher derivative term corresponding to a power of the Holst scalar curvature. The resulting effective action is basically given by General Relativity and an additional neutral pseudoscalar field (the pseudoscalaron), unequivocally related to the corresponding components of the torsion, that necessarily acquire a dynamics. The induced pseudoscalaron potential provides a realistic inflationary phase together with a very rich postinflationary epoch, resulting from the coupling of the pseudoscalaron to ordinary matter. [ABSTRACT FROM AUTHOR]

Simple Summary: Hyperglycemia is a hallmark of diabetes mellitus and contributes to several complications of this disease, such as diabetic retinopathy, diabetic nephropathy, and diabetic foot ulcer. Epidemiological evidence showed that patients suffering from diabetes are at a significantly higher risk for the development of cancer; in addition, the high glucose condition can reduce the efficacy of anticancer therapies. Therefore, uncovering novel molecular mechanisms deregulated by high glucose could give insights into the progression of high glucose-related pathologies other than the development of more efficient anticancer therapies. In this regard, homeodomain-interacting protein kinase 2 (HIPK2) has recently been disclosed in both high glucose-induced cancer resistance to chemotherapies and in diabetic complications, which will be summarized in the present review. HIPK2 is an evolutionary conserved protein kinase which modulates many molecular pathways involved in cellular functions such as apoptosis, DNA damage response, protein stability, and protein transcription. HIPK2 plays a key role in the cancer cell response to cytotoxic drugs as its deregulation impairs drug-induced cancer cell death. HIPK2 has also been involved in regulating fibrosis, angiogenesis, and neurological diseases. Recently, hyperglycemia was found to positively and/or negatively regulate HIPK2 activity, affecting not only cancer cell response to chemotherapy but also the progression of some diabetes complications. The present review will discuss how HIPK2 may be influenced by the high glucose (HG) metabolic condition and the consequences of such regulation in medical conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Dysregulated angiogenesis contributes to cancer progression and to many chronic inflammatory diseases. Many efforts in the field of angiogenesis have been made to discover new potential molecular targets to be used as biomarkers or to improve the anti-angiogenic therapies. HIPK2, an oncosuppressor able to regulate multiple molecular pathways, has been shown lately to play a role in angiogenesis both in cancer and in other angiogenic diseases. Therefore, HIPK2 emerges as a potential new biomarker of angiogenic diseases. Angiogenesis is the formation of new blood capillaries taking place from preexisting functional vessels, a process that allows cells to cope with shortage of nutrients and low oxygen availability. Angiogenesis may be activated in several pathological diseases, from tumor growth and metastases formation to ischemic and inflammatory diseases. New insights into the mechanisms that regulate angiogenesis have been discovered in the last years, leading to the discovery of new therapeutic opportunities. However, in the case of cancer, their success may be limited by the occurrence of drug resistance, meaning that the road to optimize such treatments is still long. Homeodomain-interacting protein kinase 2 (HIPK2), a multifaceted protein that regulates different molecular pathways, is involved in the negative regulation of cancer growth, and may be considered a "bona fide" oncosuppressor molecule. In this review, we will discuss the emerging link between HIPK2 and angiogenesis and how the control of angiogenesis by HIPK2 impinges in the pathogenesis of several diseases, including cancer. [ABSTRACT FROM AUTHOR]

It is tempting to speculate that many regulatory pathways acting on p53 and MDM2 for p53 ubiquitination may not only affect the degradation of p53 but also directly govern the association of p53 with DNA. Some mutations cause loss of p53 function, some provide p53 with the ability to inactivate wild-type p53 that is expressed by the remaining wild-type allele (dominant-negative p53 mutations), and others cause p53 to acquire oncogenic gain-of-function (GOF) properties. The p53 protein is a sequence-specific DNA-binding transcription factor that, in response to stressful stimuli, regulates gene expression related to multiple cellular functions including, but not limited to, cell cycle arrest, cell apoptosis, cell growth, DNA repair, cell metabolism, and the immune response [[1]]. Clinical studies have demonstrated that in many tumor types, the presence of mutated p53 correlates with a worse patient prognosis as compared to the presence of wild-type p53. p53 mutations vary greatly in terms of their impact on p53 function. [Extracted from the article]

Colon cancer, one of the most common and fatal cancers worldwide, is characterized by stepwise accumulation of specific genetic alterations in tumor suppressor genes or oncogenes, leading to tumor growth and metastasis. HIPK2 (homeodomain-interacting protein kinase 2) is a serine/threonine protein kinase and a "bona fide" oncosuppressor protein. Its activation inhibits tumor growth mainly by promoting apoptosis, while its inactivation increases tumorigenicity and resistance to therapies of many different cancer types, including colon cancer. HIPK2 interacts with many molecular pathways by means of its kinase activity or transcriptional co-repressor function modulating cell growth and apoptosis, invasion, angiogenesis, inflammation and hypoxia. HIPK2 has been shown to participate in several molecular pathways involved in colon cancer including p53, Wnt/β-catenin and the newly identified nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2). HIPK2 also plays a role in tumor–host interaction in the tumor microenvironment (TME) by inducing angiogenesis and cancer-associated fibroblast (CAF) differentiation. The aim of this review is to assess the role of HIPK2 in colon cancer and the underlying molecular pathways for a better understanding of its involvement in colon cancer carcinogenesis and response to therapies, which will likely pave the way for novel colon cancer therapies. [ABSTRACT FROM AUTHOR]

From reenactments to pilgrimages, extraordinary experiences engage consumers with frames and roles that govern their actions for the duration of the experience. Exploring such extraordinary frames and roles, however, can make the act of returning to everyday life more difficult, a process prior research leaves implicit. The present ethnography of live action role-playing explains how consumers return from extraordinary experiences and how this process differs depending on consumers' subjectivity. The emic term "bleed" captures the trace that extraordinary frames and roles leave in everyday life. The subjective tension between the extraordinary and the ordinary intensifies bleed. Consumers returning from the same experience can thus suffer different bleed intensities, charting four trajectories of return that differ in their potential for transformation: absent, compensatory, cathartic, and delayed. These findings lead to a transformative recursive process model of bleed that offers new insights into whether, how, and why consumers return transformed from extraordinary experiences with broader implications for experiential consumption and marketing. [ABSTRACT FROM AUTHOR]

Expanding knowledge of the molecular mechanisms at the basis of tumor development, especially the cross-talk between oncogenic pathways, will possibly lead to better tailoring of anticancer therapies. Nuclear factor erythroid 2-related factor 2 (NRF2) plays a central role in cancer progression, not only because of its antioxidant activity but also because it establishes cross-talk with several oncogenic pathways, including Heat Shock Factor1 (HSF1), mammalian target of rapamycin (mTOR), and mutant (mut) p53. Moreover, the involvement of NRF2 in gammaherpesvirus-driven carcinogenesis is particularly interesting. These viruses indeed hijack the NRF2 pathway to sustain the survival of tumor cells in which they establish a latent infection and to avoid a too-high increase of reactive oxygen species (ROS) when these cancer cells undergo treatments that induce viral replication. Interestingly, NRF2 activation may prevent gammaherpesvirus-driven oncogenic transformation, highlighting how manipulating the NRF2 pathway in the different phases of gammaherpesvirus-mediated carcinogenesis may lead to different outcomes. This review will highlight the mechanistic interplay between NRF2 and some oncogenic pathways and its involvement in gammaherpesviruses biology to recapitulate published evidence useful for potential application in cancer therapy. [ABSTRACT FROM AUTHOR]

Over the recent period, there has been an increasing interest in the use of pulsed infrared thermography (PT) for the non-destructive evaluation of Cultural Heritage (CH). Unlike other techniques that are commonly employed in the same field, PT enables the depth-resolved detection of different kinds of subsurface features, thus providing helpful information for both scholars and restorers. Due to this reason, several research activities are currently underway to further improve the PT effectiveness. In this manuscript, the specific use of PT for the analysis of three different types of CH, namely documentary materials, panel paintings–marquetery, and mosaics, will be reviewed. In the latter case, i.e., mosaics, passive thermography combined with ground penetrating radar (GPR) and digital microscopy (DM) have also been deepened, considering their suitability in the open field. Such items have been selected because they are characterized by quite distinct physical and structural properties and, therefore, different PT (and, in some cases, verification) approaches have been employed for their investigations. [ABSTRACT FROM AUTHOR]

Simple Summary: This Editorial summarizes the findings of the articles submitted in 2020 and 2021 to the Special Issue "The Impact of COVID-19 in Cancer". [ABSTRACT FROM AUTHOR]

On the occasion of the 700th centenary of the death of Dante Alighieri, medium wave infrared imaging analysis of illuminations of the XIV-century code of the Divina Commedia (MS. 1102), hosted in the Biblioteca Angelica in Rome, was performed and discussed. The investigation was carried out by means of thermographic and reflectographic techniques on illuminations where the iconographic representation appeared severely damaged. In particular, through the combined use of both techniques, it was possible to recover the images of the damaged parts of the pictorial layer of the illuminations and of their underdrawings, displaying details of the "lost guardians", which was useful to reconstruct the conservative history of the precious manuscript. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the major obstacles to anti-cancer therapy is the development of drug resistance that allows the cancer cell to adapt to the treatments and keep surviving. In this mini-review we attempt to give an overview of the adaptive responses and the cross-talk between them that could be targeted to counteract cancer resistance to stress and improve the outcome of cancer treatment. Different from normal cells, cancer cells must hyperactivate a variety of integrated responses in order to survive their basal stress or its exacerbation caused by exposure to anti-cancer agents. As cancer cells become particularly dependent on these adaptive responses, namely UPR, DDR autophagy, anti-oxidant and heat shock responses, this turns out to be an Achille's heel, which allows them to be selectively killed while sparing normal unstressed cells. Better knowledge of the cross-talk between these adaptive processes and their impact on the immune system is needed to design more effective anti-cancer therapies, as reviewed in this paper. [ABSTRACT FROM AUTHOR]

A density functional theory study was performed to understand the interactions of a small Ti 4 cluster with multi-vacancy graphene. We also consider the effect produced by the B-doping of the vacancy defect. In this sense, we analyze the binding mechanisms of the metal cluster. The focus is set on its stability on the substrate, geometrical structure and the interactions participating between the cluster and graphene substrate. A qualitative study of the principal bonds was carried out employing overlap population and bond order chemical descriptors. Additionally, as an attempt to comprehend better the electronic structure and related properties, we performed total density of states, band structure and magnetic moment calculations to characterize the electrical and magnetic properties of the B-doped and non-doped systems. [ABSTRACT FROM AUTHOR]

Objectives: Primary myelofibrosis (PMF) is a BCR/ABL1-negative myeloproliferative neoplasm (MPN) with a shorter overall survival and a higher leukemic transformation than other BCR/ABL1-negative MPNs. Diagnosis of PMF can be challenging given its clinical, morphologic, molecular overlap with other myeloid neoplasms also associated with myelofibrosis, and reactive conditions.Methods: We summarize and discuss the clinical, morphologic, and molecular features useful for diagnosing PMF as well as salient features helpful in distinguishing PMF from myelodysplastic syndrome with associated fibrosis and autoimmune myelofibrosis using a case-based approach.Results: PMF in both its prefibrotic and fibrotic stages, the latter characterized by reticulin/collagen marrow fibrosis, is characterized by a proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow. Driver mutations in   JAK2, CALR, or MPLare seen in approximately 90% of PMF cases. In triple-negative cases, the presence of cytogenetic abnormalities and other somatic mutations identified by next-generation sequencing can help establish a diagnosis of PMF in the appropriate clinical and morphologic context.Conclusions: Given the significant difference in prognosis and treatment, integration of clinical, morphological, and molecular/genetic findings is essential in distinguishing PMF from other etiologies that can demonstrate myelofibrosis. [ABSTRACT FROM AUTHOR]

Two sandstone slabs from a new Norian tetrapod tracksite in the Löwenstein Formation of southern Germany preserve a set of tracks including both tridactyl and pentadactyl ichnites, referred to theropod dinosaur and sphenosuchian crocodylomorph trackmakers, respectively. A very large manus print hints at the presence of a hitherto unknown large quadrupedal archosaur in the Norian fauna of southern Germany. The material includes one of the oldest records of crocodylomorph tracks presently known, in agreement with the skeletal record from the same formation. [ABSTRACT FROM AUTHOR]

Context. Young open clusters (ages of less than 200 Myr) have been observed to exhibit several peculiarities in their chemical compositions. These anomalies include a slightly sub-solar iron content, super-solar abundances of some atomic species (e.g. ionised chromium), and atypical enhancements of [Ba/Fe], with values up to ~0.7 dex. Regarding the behaviour of the other s-process elements like yttrium, zirconium, lanthanum, and cerium, there is general disagreement in the literature: some authors claim that they follow the same trend as barium, while others find solar abundances at all ages. Aims. In this work we expand upon our previous analysis of a sample of five young open clusters (IC 2391, IC 2602, IC 4665, NGC 2516, and NGC 2547) and one star-forming region (NGC 2264), with the aim of determining abundances of different neutron-capture elements, mainly Cu I, Sr I, Sr II, Y II, Zr II, Ba II, La II, and Ce II. For NGC 2264 and NGC 2547 we present the measurements of these elements for the first time. Methods. We analysed high-resolution, high signal-to-noise spectra of 23 solar-type stars observed within the Gaia-ESO survey. After a careful selection, we derived abundances of isolated and clean lines via spectral synthesis computations and in a strictly differential way with respect to the Sun. Results. We find that our clusters have solar [Cu/Fe] within the uncertainties, while we confirm that [Ba/Fe] is super-solar, with values ranging from +0.22 to +0.64 dex. Our analysis also points to a mild enhancement of Y, with [Y/Fe] ratios covering values between 0 and +0.3 dex. For the other s-process elements we find that [X/Fe] ratios are solar at all ages. Conclusions. It is not possible to reconcile the anomalous behaviour of Ba and Y at young ages with standard stellar yields and Galactic chemical evolution model predictions. We explore different possible scenarios related to the behaviour of spectral lines, from the dependence on the different ionisation stages and the sensitivity to the presence of magnetic fields (through the Landé factor) to the first ionisation potential effect. We also investigate the possibility that they may arise from alterations of the structure of the stellar photosphere due to the increased levels of stellar activity that affect the spectral line formation, and consequently the derived abundances. These effects seem to be stronger in stars at ages of less than ~ 100 Myr. However, we are still unable to explain these enhancements, and the Ba puzzle remains unsolved. With the present study we suggest that other elements, for example Sr, Zr, La, and Ce, might be more reliable tracer of the s-process at young ages, and we strongly encourage further critical observations. [ABSTRACT FROM AUTHOR]

Summary: We describe the clinical phenotype, management strategies and outcomes of 22 patients with autoimmune myelofibrosis (AIMF); median age: 45 years; 77% females; 83% with autoimmune disease, pancytopenia in 32% and transfusion‐requiring anaemia in 59%. All informative cases were negative for JAK2 (n = 18) and CALR/MPL mutations (n = 12). Fourteen of nineteen (74%) evaluable patients achieved complete response (CR) based on the resolution of cytopenias. First‐line treatments included steroids +/− immunosuppressive agents, cyclosporin and mycophenolate with CR in 7 of 13 (54%), 1 of 2 (50%) and 1 of 2 (50%) respectively. Rituximab salvage therapy yielded CR in 4 of 5 (80%) cases. The current study provides information on steroid‐sparing treatments for AIMF. [ABSTRACT FROM AUTHOR]

In the manufacture of ancient books, it was quite common to insert written scraps belonging to earlier library material into bookbindings. For scholars like codicologists and paleographers, it is extremely important to have the possibility of reading the text lying on such scraps without dismantling the book. In this regard, in this paper, we report on the detection of these texts by means of infrared (IR) pulsed thermography (PT), which, in recent years, has been specifically proven to be an effective tool for the investigation of Cultural Heritage. In particular, we present a quantitative analysis based, for the first time, on PT images obtained from books of historical relevance preserved at the Biblioteca Angelica in Rome. The analysis has been carried out by means of a theoretical model for the PT signal, which makes use of two image parameters, namely, the distortion and the contrast, related to the IR readability of the buried texts. As shown in this paper, the good agreement between the experimental data obtained in the historical books and the theoretical analysis proved that the capability of the adopted PT method could be fruitfully applied, in real case studies, to the detection of buried texts and to the quantitative characterization of the parameters affecting their thermal readability. [ABSTRACT FROM AUTHOR]

• CTB containing RAP and CTB virgin aggregates resist similarly to cyclic loadings. • CTB-RAP shows a slightly lower mechanical strength than CTB-Virgin. • CTB-Virgin shows a much more rigid behaviour than CTB-RAP. • The CTB-Virgin shows a faster damage growth than the CTB-RAP. • The use of RAP in CTB mixtures does not modify mechanical performance of the mix. A laboratory investigation was performed to better understand the performance of Cement-Treated Base (CTB) mixtures containing Recycled Asphalt Pavement (RAP) during a long-lasting service period. Two CTB mixtures, one containing only virgin aggregates and the other containing RAP and virgin aggregates, were tested by triaxial tests (static and cyclic) and resonant column tests to evaluate stiffness and dampening at very small deformations. Similar mechanical properties and response to cyclic loadings were obtained for the two mixtures. The results led to the conclusion that the use of RAP as a replacement for virgin aggregates for a CTB mixture does not cause any significant alteration in terms of mechanical performance. [ABSTRACT FROM AUTHOR]

Ataxia telangiectasia (AT) is a rare genetic neurodegenerative disease. To date, there is no available cure for the illness, but the use of glucocorticoids has been shown to alleviate the neurological symptoms associated with AT. While studying the effects of dexamethasone (dex) in AT fibroblasts, by chance we observed that the nucleoplasmic Lamin A/C was affected by the drug. In addition to the structural roles of A-type lamins, Lamin A/C has been shown to play a role in the regulation of gene expression and cell cycle progression, and alterations in the LMNA gene is cause of human diseases called laminopathies. Dex was found to improve the nucleoplasmic accumulation of soluble Lamin A/C and was capable of managing the large chromatin Lamin A/C scaffolds contained complex, thus regulating epigenetics in treated cells. In addition, dex modified the interactions of Lamin A/C with its direct partners lamin associated polypeptide (LAP) 2a, Retinoblastoma 1 (pRB) and E2F Transcription Factor 1 (E2F1), regulating local gene expression dependent on E2F1. These effects were differentially observed in both AT and wild type (WT) cells. To our knowledge, this is the first reported evidence of the role of dex in Lamin A/C dynamics in AT cells, and may represent a new area of research regarding the effects of glucocorticoids on AT. Moreover, future investigations could also be extended to healthy subjects or to other pathologies such as laminopathies since glucocorticoids may have other important effects in these contexts as well. [ABSTRACT FROM AUTHOR]

Inflammation and cancerogenesis are strongly interconnected processes, not only because inflammation promotes DNA instability, but also because both processes are driven by pathways such as NF-kB, STAT3, mTOR and MAPKs. Interestingly, these pathways regulate the release of pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β that in turn control their activation and play a crucial role in shaping immune response. The transcription factor p53 is the major tumor suppressor that is often mutated in cancer, contributing to tumor progression. In this overview, we highlight how the interplay between pro-inflammatory cytokines and pro-inflammatory/pro-oncogenic pathways, regulating and being regulated by UPR signaling and autophagy, affects the stability of mutp53 that in turn is able to control autophagy, UPR signaling, cytokine release and the activation of the same oncogenic pathways to preserve its own stability and promote tumorigenesis. Interrupting these positive feedback loops may represent a promising strategy in anticancer therapy, particularly against cancers carrying mutp53. [ABSTRACT FROM AUTHOR]

Objectives: To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings.Methods: The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests.Results: Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category.Conclusions: Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders. [ABSTRACT FROM AUTHOR]

This work identifies a dual process in intergenerational cultural transmission and reception mechanisms: on the one hand, a break in historical continuity between past and present, and, on the other, the use of its legitimacy to make a mark on history. The approach emphasizes two aspects of cultural and economic transformation, the change induced by sudden, pervasive events, and the plasticity of cultural reception. Therefore, it is intended to argue that without the socio-cultural disposition to accept change, economic transformations cannot work. Drawing on this idea, this article aims to elucidate how cultural transmission crosses time, allowing humanity to recognize and legitimize a new socio-economic order. [ABSTRACT FROM AUTHOR]

A major challenge in regenerative medicine is replacing cells lost through injury or disease. While significant progress has been made, much remains unknown about the accuracy of native regenerative programs in cell replacement. Here, we capitalized on the regenerative capacity and stereotypic retinal organization of zebrafish to determine the specificity with which retinal Müller glial cells replace lost neuronal cell types. By utilizing a targeted genetic ablation technique, we restricted death to all or to distinct cone photoreceptor types (red, blue, or UV‐sensitive cones), enabling us to compare the composition of cones that are regenerated. We found that Müller glia produce cones of all types upon nondiscriminate ablation of these photoreceptors, or upon selective ablation of red or UV cones. Pan‐ablation of cones led to regeneration of the various cone types in relative abundances that resembled those of nonablated controls, that is, red > green > UV ~ blue cones. Moreover, selective loss of red or UV cones biased production toward the cone type that was ablated. In contrast, ablation of blue cones alone largely failed to induce cone production at all, although it did induce cell division in Müller glia. The failure to produce cones upon selective elimination of blue cones may be due to their low abundance compared to other cone types. Alternatively, it may be that blue cone death alone does not trigger a change in progenitor competency to support cone genesis. Our findings add to the growing notion that cell replacement during regeneration does not perfectly mimic programs of cell generation during development. [ABSTRACT FROM AUTHOR]

Hydrogen adsorption stability, geometry, electronic structure and mechanism has been investigated on Ni 4 cluster embedded in graphene with three, four and six vacancies by density functional theory (DFT) calculations. An energetic analysis of hydrogen adsorption by addition of one to four H 2 molecules was performed for each system in order to determine their hydrogen storage capacity. Dispersion force contribution to the adsorption energy is quantitative evaluated to know whether H 2 molecules adsorption behavior is dominated by chemical or van der Waals interactions. A further analysis of this type of interactions is also addressed by total and partial density of states. Bonding and charge transfer characteristics for the different steps involved in the adsorption mechanism are also included. Special attention is given to the effects caused by this new Ni/graphene interface to the hydrogen adsorption behavior. Image 1 • Hydrogen adsorption on Ni 4 embedded in multivacancy defected graphene was studied. • Three adsorption mechanism were identified. • First molecule adsorbed can be dissociated. • Up to four hydrogen molecules can be adsorbed with physicochemical interaction. [ABSTRACT FROM AUTHOR]

In this paper an overview of recent applications of mid-wave infrared imaging techniques to the study of books is presented. Studies performed by thermography and mid-wave infrared reflectography are reviewed to demonstrate how they can be used to investigate the main features of books. The capability of these techniques is exploited in the analysis of structural elements of the bookbindings and writing supports as well as in the characterization of the writings and illuminations. Thermographic and reflectographic results are compared with results obtained using other imaging techniques operating in different spectral regions, thus pointing out how mid-wave infrared imaging techniques can help in examining many aspects of books. Finally, it is shown that the obtained information can also be used to evaluate the condition of the book and, when required, to properly plan conservation treatments. [ABSTRACT FROM AUTHOR]

We find multicenter (Majumdar–Papapetrou type) solutions of Eddington-inspired Born–Infeld gravity coupled to electromagnetic fields governed by a Born–Infeld-like Lagrangian. We construct the general solution for an arbitrary number of centers in equilibrium and then discuss the properties of their one-particle configurations, including the existence of bounces and the regularity (geodesic completeness) of these spacetimes. Our method can be used to construct multicenter solutions in other theories of gravity. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy represents a major hurdle to successful cancer treatment. A key role for efficient response to anticancer therapies is played by TP53 oncosuppressor gene that indeed is mutated in 50% of human cancers or inactivated at protein level in the remaining 50%. Homeodomain‐interacting protein kinase 2 (HIPK2) is the wild‐type p53 (wtp53) apoptotic activator, and its inhibition by hypoxia or hyperglycemia may contribute to tumor chemoresistance mainly by impairing p53 apoptotic activity. Another important molecule able to induce chemoresistance is nuclear factor erythroid 2 (NF‐E2) p45‐related factor 2 (NRF2) transcription factor, whose activation by oxidative and/or electrophilic stress regulates a transcriptional antioxidant program allowing cancer cells to adapt and survive to stresses. NRF2 may shift from cytoprotective to tumor‐promoting function, according to tumor phases. NRF2 may crosstalk with both wtp53 and mutant p53 (mutp53), inhibiting the wtp53 apoptotic function and strengthening the mutp53 oncogenic function. NRF2 has also been shown to induce HIPK2 mRNA expression cooperating in inducing cytoprotection. Although HIPK2, p53, and NRF2 have been individually extensively studied, their interplay has not been clearly addressed yet. On the basis of the background and our results, we aim at hypothesizing the unexpected pro‐survival activity played by the NRF2/HIPK2/p53 interplay that can be hijacked by cancer cells to bypass drugs cytotoxicity. [ABSTRACT FROM AUTHOR]

We generalize the algorithm that establishes the correspondence between metric-affine Eddington-inspired Born-Infeld (EiBI) gravity and General Relativity (GR) to any bosonic matter sector. Along the way, a polished version of the proof of existence of a metric compatible frame associated to any metric-affine Ricci-Based Gravity (RBG) is presented. Particular attention is given to the problem of generating solutions of a RBG from the GR counterpart, providing a general recipe for the EiBI case. This extends previous results obtained for specific matter that included anisotropic fluids, scalar fields and electromagnetic fields. [ABSTRACT FROM AUTHOR]

The determination of the fundamental properties (mass, separation, age, gravity, and atmospheric properties) of brown dwarf companions allows us to infer crucial informations on their formation and evolution mechanisms. Spectroscopy of substellar companions is available to date only for a limited number of objects (and mostly at very low resolution, R  < 50) because of technical limitations, i.e. contrast and angular resolution. We present medium resolution (R  = 350), coronagraphic long-slit spectroscopic observations with SPHERE of two substellar companions, HD 1160 B and HD 19467 B. We found that HD 1160 B has a peculiar spectrum that cannot be fitted by spectra in current spectral libraries. A good fit is possible only considering separately the Y + J and the H spectral band. The spectral type is between M5 and M7. We also estimated a T eff of 2800–2900 K and a log  g of 3.5–4.0 dex. The low surface gravity seems to favour young age (10–20 Myr) and low mass (∼20 MJup ) for this object. HD 19467 B is instead a fully evolved object with a T eff of ∼1000 K and log  g of ∼5.0 dex. Its spectral type is T6 ± 1. [ABSTRACT FROM AUTHOR]

In recent years, a large body of knowledge regarding the molecular genetics of myeloid malignancies has emerged and molecular findings have become increasingly important not only for diagnosis but also to establish prognosis and treatment of patients with myeloid malignancies. Clinical and pathological findings have been refined in relation to their diagnostic/prognostic value. The integration of all these different parameters represents the backbone of the 2016 revised 4th Edition of the WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. The current review aims to highlight the main changes between the 2008 WHO Classification and the most recent 2016 revised 4th edition, with regard to the classification of myeloid malignancies. [ABSTRACT FROM AUTHOR]

• State of the art of thermographic applications to the study of bronzes. • Study of the main steps of the lost-wax casting process. • Use of passive and active thermography for the study of artistic bronzes. • Thermographic investigations of defects and repairs of artistic bronzes. • Thermographic analysis of the masterpieces of the bronze statuary of Rome. • Quantitative evaluations of the thermal properties of copper alloys. The study of bronze statues obtained by the lost-wax casting method results of particular relevance from the artistic and historical points of view. In particular, the characterization of structural and subsurface elements of bronzes is very useful to gather insight concerning their preservation state and manufacturing process. For these purposes, infrared thermography has been successfully employed to investigate different kind of items of artistic bronzes, such as repairs, defects and inserts, providing also the possibility to perform the depth-resolved study of the observed subsurface features thanks to the possibility it also provides to evaluate the thermal transport properties of the investigated materials. In this work, the experimental configurations and the capabilities of such a technique have been reviewed. The state of the art of the results obtained by infrared thermography for the analysis of artistic bronzes is presented. It is thus shown that infrared thermography can be nowadays considered as a reliable and consolidated technique to map in a non-destructive way a wide spectrum of features of bronzes. [ABSTRACT FROM AUTHOR]

In the present work, a novel set of software tools for the rapid development of shoes and footwear is presented aimed at strongly reducing the design time and then the time-to-market of the products. These tools are mainly based on an implementation of Constrained Free Form Deformation techniques and on the use of modern surface scanning methods. The proposed approach allows, in many cases, to avoid the mathematical surface reconstruction and to quickly generate the complex geometries that CAM systems will process in order to generate the tool paths for mold manufacturing. [ABSTRACT FROM AUTHOR]

Simple Summary: Post-translational modifications (PTMs) strongly influence the stability and function of proteins. These modifications have been reported to affect wild-type (wt) p53 as well as the mutant forms of this protein (mutp53), often detected in cancer cells. Thus, PTMs may be key regulators of the oncosuppressor activity of wtp53 and of the pro-oncogenic functions that some mutant forms of p53 may acquire, in terms of tumor survival, progression and resistance to anti-cancer therapies. As treatments that specifically target mutp53 do not exist, manipulating PTMs may represent a promising approach to achieve this goal and even to reactivate the wt functions of mutant proteins, in some cases, as reported in this review. Wild-type (wt) p53 and mutant forms (mutp53) play a key but opposite role in carcinogenesis. wtP53 acts as an oncosuppressor, preventing oncogenic transformation, while mutp53, which loses this property, may instead favor this process. This suggests that a better understanding of the mechanisms activating wtp53 while inhibiting mutp53 may help to design more effective anti-cancer treatments. In this review, we examine possible PTMs with which both wt- and mutp53 can be decorated and discuss how their manipulation could represent a possible strategy to control the stability and function of these proteins, focusing in particular on mutp53. The impact of ubiquitination, phosphorylation, acetylation, and methylation of p53, in the context of several solid and hematologic cancers, will be discussed. Finally, we will describe some of the recent studies reporting that wt- and mutp53 may influence the expression and activity of enzymes responsible for epigenetic changes such as acetylation, methylation, and microRNA regulation and the possible consequences of such changes. [ABSTRACT FROM AUTHOR]

NiTi alloy has important properties such as shape-memory, super-plasticity, resistance, and biocompatibility, therefore is frequently used in biomedical devices. We studied the oxidized form of this alloy and possible Ni segregation in three possible models for the TiO 2 /NiTi interface: i) the perfect interface; ii) the Ni enriched interface and iii) with oxygen vacancies in the TiO 2 coating. We used DFT + U calculations for TiO 2 , because Hubbard correction encourages localization of the excess electronic charge and improves the DFT results. A standard spin polarized DFT was used for NiTi. We obtained the optimized geometries for each model and computed segregation energy, electronic structure, magnetic moment and bond order for the interface and for Ni segregation. Our calculations indicated that Ti3+ species are present at the interface, while in the bulk of the oxide layer the species is the Ti4+. Also, the electronic structure show that the metallic character of the alloy is unaffected by the interaction with oxygen. These results are consistent with experimental data from literature. Ni enriched interface containing O vacancies show a strong geometric distortion in the TiO 2 layers. In all cases, Ni segregation is an a thermodynamically unfavorable process, helping to understand the biocompatibility of NiTi alloy. Unlabelled Image • Ni segregation is an unfavorable process in all considered models. • A Ni-rich interface with oxygen vacancies is the less unfavorable situation for segregation. • Bond order analysis indicates an important Ni O bonding at the perfect interface. • The first layer of TiO2 on NiTi produces a relevant blocking effect in Ni segregation. • The introduction of oxygen vacancies induces a strong distortion in the oxide layers regularity. [ABSTRACT FROM AUTHOR]

A wide range of congenital or acquired conditions, some pretty rare, may affect the vulva and vagina in children. Swelling, visible or palpable masses and abnormal discharges are common symptoms of conditions affecting the vulva and/or the lower genital tract. The majority of these diseases are benign. Ultrasonography is pivotal to elucidate the anatomical origin of these conditions and make the diagnosis. Magnetic resonance imaging can be relevant to improve diagnostic confidence and, if needed, to plan more accurate surgical treatment. The aim of this pictorial essay is to review the related imaging findings to help make radiologists familiar with these conditions. [ABSTRACT FROM AUTHOR]

Lime stabilization of clay soils is becoming, if not already, one of the most used construction techniques for road embankments and for subbase stabilization. In warm countries, lime stabilization is used without any problems; but in cold countries, some concerns are still present in relation to behavior of lime-stabilized soils at low temperatures, particularly in conditions of freezing and thawing. The research in this paper presents the results of an experimental campaign made on a typical Italian clay soil stabilized with lime. The research studies the evolution of mechanical performances of lime-stabilized soil under the effect of freeze and thaw cycles and after a series of several freezes and thaws. The results of the research clearly show that lime-stabilized soils can have proper mechanical performances after freeze and thaw cycles. In particular, the test campaign shows that lime-stabilized soils have decreased resistance after freeze and thaw cycles and that they almost fully recover their resistance if the temperature comes back constantly to 20°C. [ABSTRACT FROM AUTHOR]

Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy selecting a more malignant and invasive phenotype, and playing a negative role in patient prognosis. This commentary wishes to recognize the 2019 Nobel Prize in Medicine awarded to three physicians-scientists, Prof. William G. Kaelin Jr., Prof. Sir Peter J. Ratcliffe, and Prof. Gregg L. Semenza, for their discovery of the mechanisms mediating cell ability to sense and adapt to changes in oxygen availability. Their studies established the basis for our understanding of the role of hypoxia in a variety of diseases, including anemia, renal failure, cardiovascular disease, metabolic diseases, and cancer, paving the way for new promising therapeutic strategies through the development of drugs that can either activate or block the oxygen-sensing machinery. [ABSTRACT FROM AUTHOR]

A new ichnospecies, Brasilichnium anaiti, is erected on material from the Botucatu Formation of Brazil. The general morphology supports ichnotaxonomic similarity between the new ichnotaxon and Brasilichnium elusivum Leonardi, 1981, even if a separation at the ichnospecies level is evident, based on differences in shape and arrangement of pes digit marks along with a clear dimensional gap between both ichnotaxa. Similar forms from the Lower Jurassic of the United States are known and should be included under this new ichnotaxonomic label, based on shared morphological features. B. anaiti is constantly associated with B. elusivum in dune foresets of hyperarid paleoenvironments, to which these forms are restricted. This makes B. anaiti a further element of the Brasilichnium ichnocoenosis in the larger framework of the Chelichnus ichnofacies. Re-evaluation of possible trackmakers highlights the difficulties of unequivocal referring this ichnotaxon to a specific producer, but restrains potential trackmakers to early mammaliamorph therapsids. [ABSTRACT FROM AUTHOR]

Ataxia telangiectasia (A-T) is an incurable and rare hereditary syndrome. In recent times, treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this condition, but the molecular mechanism of action of these analogues remains unknown. Hence, the aim of this study was to gain insight into the molecular mechanism of action of glucocorticoid analogues in the treatment of A-T by investigating the role of Dexamethasone (Dexa) in A-T lymphoblastoid cell lines. We used 2DE and tandem MS to identify proteins that were influenced by the drug in A-T cells but not in healthy cells. Thirty-four proteins were defined out of a total of 746±63. Transcriptome analysis was performed by microarray and showed the differential expression of 599 A-T and 362 wild type (WT) genes and a healthy un-matching between protein abundance and the corresponding gene expression variation. The proteomic and transcriptomic profiles allowed the network pathway analysis to pinpoint the biological and molecular functions affected by Dexamethasone in Dexa-treated cells. The present integrated study provides evidence of the molecular mechanism of action of Dexamethasone in an A-T cellular model but also the broader effects of the drug in other tested cell lines. [ABSTRACT FROM AUTHOR]

the article identifies some key features, which could help to define the theoretical patterns to improve the study of the presence and function of fantasy in contemporary Spanish drama. According to these theoretical patterns, inferred inductively from the recent Spanish dramatic production, this contribution analyses their application and systematization, to integrate them in a whole intepreta-tive system. [ABSTRACT FROM AUTHOR]