A future multi-TeV muon collider requires new ideas to tackle the problems of muon production, accumulation and acceleration. In the Low EMittance Muon Accelerator concept a 45 GeV positron beam, ...stored in an accumulation ring with high energy acceptance and low angular divergence, is extracted and driven to a target system in order to produce muon pairs near the kinematic threshold. However, this scheme requires an intensity of the impinging positron beam so high that the energy dissipation and the target maintenance are crucial aspects to be investigated. Both peak temperature rises and thermomechanical shocks are related to the beam spot size at the target for a given material: these aspects are setting a lower bound on the beam spot size itself. The purpose of this paper is to provide a fully theoretical approach to predict the temperature increase, the thermal gradients, and the induced thermomechanical stress on targets, generated by a sequence of 45 GeV positron bunches. A case study is here presented for Beryllium and Graphite targets. We first discuss the Monte Carlo simulations to evaluate the heat deposited on the targets after a single bunch of 3 × 10
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positrons for different beam sizes. Then a theoretical model is developed to simulate the temperature increase of the targets subjected to very fast sequences of positron pulses, over different timescales, from ps regime to hundreds of seconds. Finally a simple approach is provided to estimate the induced thermomechanical stresses in the target, together with simple criteria to be fulfilled (i.e., Christensen safety factor) to prevent the crack formation mechanism.
There is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical ...practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques.
We conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement.
Sixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified.
Harmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.
The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes ...from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene
, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.
Ecuador is one of the most biodiverse countries in the world, but faces severe pressures and threats to its natural ecosystems. Numerous species have declined and require to be objectively evaluated ...and quantified, as a step towards the development of conservation strategies. Herein, we present an updated National Red List Assessment for amphibian species of Ecuador, with one of the most detailed and complete coverages for any Ecuadorian taxonomic group to date. Based on standardized methodologies that integrate taxonomic work, spatial analyses, and ecological niche modeling, we assessed the extinction risk and identified the main threats for all Ecuadorian native amphibians (635 species), using the IUCN Red List Categories and Criteria. Our evaluation reveals that 57% (363 species) are categorized as Threatened, 12% (78 species) as Near Threatened, 4% (26 species) as Data Deficient, and 27% (168 species) as Least Concern. Our assessment almost doubles the number of threatened species in comparison with previous evaluations. In addition to habitat loss, the expansion of the agricultural/cattle raising frontier and other anthropogenic threats (roads, human settlements, and mining/oil activities) amplify the incidence of other pressures as relevant predictors of ecological integrity. Potential synergic effects with climate change and emergent diseases (apparently responsible for the sudden declines), had particular importance amongst the threats sustained by Ecuadorian amphibians. Most threatened species are distributed in montane forests and paramo habitats of the Andes, with nearly 10% of them occurring outside the National System of Protected Areas of the Ecuadorian government. Based on our results, we recommend the following actions: (i) An increase of the National System of Protected Areas to include threatened species. (ii) Supporting the ex/in-situ conservation programs to protect species considered like Critically Endangered and Endangered. (iii) Focalizing research efforts towards the description of new species, as well as species currently categorized as Data Deficient (DD) that may turn out to be threatened. The implementation of the described actions is challenging, but urgent, given the current conservation crisis faced by amphibians.
Rock permeability and porosity are some of the most important features to be determined during the exploitation of a certain hydrocarbon reservoir, as these physical properties help petrophysicists ...understand the most likely distribution and/or presence of oil/gas reservoirs, as well as decide whether that certain field might be exploitable or not. Despite their importance, in order to obtain permeability and porosity values it is usually required to run tests on borehole core samples that are either destructives or that need to be done under very controlled conditions, which makes them very expensive and time consuming. In the last decades, some authors have been able to estimate both these properties measurements from well-logging reservoir curves –such as Gamma-Ray response (GR), Bulk Density (RHOB) or Neutron Porosity (NPHI)–. In this study, we present a novel method that can be used to estimate formation permeability and porosity from borehole image logs –instead of simple logs– using deep autoencoders. The data used in this work belongs was extracted from a Brazilian pre-salt carbonate well. First, we use a 3–level stacked autoencoder to extract internal features from both ultrasonic and microresistivity images, thus characterizing the features contained inside these images. Afterwards, we use a support vector machine regressor (SVM) to link the encoded features extracted from the autoencoders for each type of data (ultrasonic and microresistivity borehole images) to the petrophysical measurements logs. Using this method we were able to achieve a correlation coefficient between original and estimated validation samples of R2=96.30% for effective porosity logs and R2=96.06% for permeability logs, and a normalized squared mean error of NMRSE=7.30% and NMRSE=5.51%, respectively, all results in the blind test sample.
•Permeability and E_ective Porosity wireline logs estimation with over 96% accuracy.•Use of Borehole Image Data Logs (Ultrasonic and Microresistivity) as only source of information for the petrophysical logs estimation.•Application of Deep Learning methods to borehole well data (Stacked Autoencoders).•The use of sliding window to extract hidden features from the Borehole Images allow us to preserve the information of the geological structures on the surroundings of each sample.•The correlation between Ultrasonic and Resistivity Image Data Logs and petrophysical logs (Porosity and Permeability) is shown to be objective in this paper, rather than something subjective or intuitive (as it used to be in the past, when petrophysicists could not quantify objectively the amount of information from these data sources that should be taken into account).
Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous ...mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms.
Objectives
The aim of Working Group 4 was to address topics related to biologic risks and complications associated with implant dentistry. Focused questions on (a) diagnosis of peri‐implantitis, (b) ...complications associated with implants in augmented sites, (c) outcomes following treatment of peri‐implantitis, and (d) implant therapy in geriatric patients and/or patients with systemic diseases were addressed.
Materials and methods
Four systematic reviews formed the basis for discussion in Group 4. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary.
Results
Bleeding on probing (BOP) alone is insufficient for the diagnosis of peri‐implantitis. The positive predictive value of BOP alone for the diagnosis of peri‐implantitis varies and is dependent on the prevalence of peri‐implantitis within the population. For patients with implants in augmented sites, the prevalence of peri‐implantitis and implant loss is low over the medium to long term. Peri‐implantitis treatment protocols which include individualized supportive care result in high survival of implants after 5 years with about three‐quarters of implants still present. Advanced age alone is not a contraindication for implant therapy. Implant placement in patients with cancer receiving high‐dose antiresorptive therapy is contraindicated due to the associated high risk for complications.
Conclusions
Diagnosis of peri‐implantitis requires the presence of BOP as well as progressive bone loss. Prevalence of peri‐implantitis for implants in augmented sites is low. Peri‐implantitis treatment should be followed by individualized supportive care. Implant therapy for geriatric patients is not contraindicated; however, comorbidities and autonomy should be considered.
The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep ...lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers, genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, telomeric stress: δ-H2AX, p16, p53, TERT. Lung cancer-related epigenetic, genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase, p53 induction. p16 was also induced in early tumorigenic progression, was inactivated in bronchiolar dysplasias, tumors. Remarkably, lack of mutations of Ras, epidermal growth factor receptor, a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, APC, but not in Rassf1, Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.
Pancreatic stellate cells (PSC) play a major role in the formation of fibrotic tissue in pancreatic tumors. On its side, melatonin is a putative therapeutic agent for pancreatic cancer and ...inflammation. In this work, the actions of melatonin on PSC subjected to hypoxia were evaluated. Reactive oxygen species (ROS) generation reduced (GSH) and oxidized (GSSG) levels of glutathione, and protein and lipid oxidation were analyzed. The phosphorylation of nuclear factor erythroid 2-related factor (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and the regulatory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα) was studied. The expression of Nrf2-regulated antioxidant enzymes, superoxide dismutase (SOD) enzymes, cyclooxygenase 2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also studied. Total antioxidant capacity (TAC) was assayed. Finally, cell viability was studied. Under hypoxia and in the presence of melatonin generation of ROS was observed. No increases in the oxidation of proteins or lipids were detected. The phosphorylation of Nrf2 and the expression of the antioxidant enzymes catalytic subunit of glutamate-cysteine ligase, catalase, NAD(P)H-quinone oxidoreductase 1, heme oxygenase-1, SOD1, and of SOD2 were augmented. The TAC was increased. Protein kinase C was involved in the effects of melatonin. Melatonin decreased the GSH/GSSG ratio at the highest concentration tested. Cell viability dropped in the presence of melatonin. Finally, melatonin diminished the phosphorylation of NF-kB and the expression of COX-2, IL-6, and TNF-α. Our results indicate that melatonin, at pharmacological concentrations, modulates the red-ox state, viability, and the expression of proinflammatory mediators in PSC subjected to hypoxia.
Abstract
Subtribe Spiranthinae is the most species-rich lineage of terrestrial Neotropical orchids, encompassing > 500 species and 40 genera. We conducted maximum parsimony and maximum likelihood ...phylogenetic analyses of DNA sequence data of plastid matK-trnK and trnL-trnF and nuclear ribosomal ITS sequences for 36 genera and 182 species of Spiranthinae plus appropriate outgroups. The results strongly support monophyly of Spiranthinae (minus Discyphus, Discyphinae and Galeottiella, Galeottiellinae) and five major lineages, namely monospecific Cotylolabium (sister to the remaining Spiranthinae) and the Eurystyles, Pelexia, Spiranthes and Stenorrhynchos clades. Eighteen of the 27 genera of Spiranthinae for which more than one species was included in our analyses are monophyletic. Paraphyly of large genera, such as Cyclopogon and Sarcoglottis, resulted from segregation of particular species or groups of species exhibiting minor modifications of structures directly involved in pollination (e.g. nectary, rostellum and viscidium). Conversely, polyphyly has resulted from convergent evolution of floral attributes in distantly related species (e.g. Mesadenus). Some of the morphological characters used traditionally for generic delimitation and in non-molecular cladistic analyses of Spiranthinae are discussed against the evolutionary framework set by our molecular trees, emphasizing putative synapomorphies and problems derived from inappropriate character coding or incorrect homology assessments. Our ancestral area analysis indicates that Spiranthinae originated in eastern South America, with subsequent migrations and secondary radiations in Mesoamerica and North America, plus a derived migration from the latter region to the Old World (Spiranthes).
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