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The present paper describes the experimental setup for flow-induced vibration in a fuel pin bundle test section with flowing lead. The test section is a 37-pin mock-up representative of the GEN-IV ALFRED fuel assembly and is manufactured to investigate the turbulence-induced vibrations in the pins. The pins are instrumented with longitudinal strain gauges (SGs), and with three SGs per monitoring point, the displacement signal can be recovered in terms of amplitude and frequencies. To achieve this goal, a complex algorithm is implemented in the data acquisition control system of the test section. The test section will be installed in the Heavy Liquid metal Experimental loop for Nuclear Applications (HELENA) facility at the ENEA Brasimone R.C., in which a mechanical pump for lead circulation is present. The test matrix is proposed with the mass flow rate varying from 10 to 50 kg/s and a constant temperature of 450°C for all the tests. Briefly, the experimental procedure is presented to carry out the experimental campaign. [ABSTRACT FROM AUTHOR]

Sin resumen.

Gypsum has been widely used in traditional and monumental architecture in many countries of the Mediterranean area; however, due to its low water resistance and low mechanical strength, it can be subject to physical, chemical and biological degradation. To improve the preservation of gypsum-based plaster artifacts, a new hybrid inorganic-organic hydrophobic treatment is proposed in this work. This treatment is based on nanometric magnesium hydroxide (Mg(OH)₂) and organically modified silica (OrMoSil), a class of materials with intermediate performances between ceramic materials and polymers. The behaviour of the product was verified both as a protective on gypsum surface, as well as a consolidant added to the mixture of gypsum-based plasters. The treatment does not alter the aesthetic appearance of the surface, as verified through colorimetric analysis. As demonstrated by capillary water absorption and static contact angle measurements, the new hydrophobic protective coating proved to be very effective. Moreover, the new treatment is effective as a consolidant, leading to an improvement of the mechanical properties and to a reduction of the depth of carbonation. The new hydrophobic nanocomposite product is therefore a promising material for the protection and consolidation of gypsum monuments and artifacts of cultural interest.

This work deals with the development of innovative cement-free plastering mortars with enhanced thermal properties. To this end, one-part alkali-activated slag-based materials were manufactured, by adding aluminum powder as expanding agent to reduce the density and expanded glass to improve thermal insulation. Different recipes were developed by varying the water content and the alkali-activator. The results show that the admixture containing sodium silicate meets the requirements for a lightweight plastering mortar in terms of mechanical strength (class CSII), despite exhibiting slightly elevated thermal conductivity with respect to that required for a type T2 (0.28 vs. 0.20 W/mK). The admixture with potassium silicate shows instead noteworthy values of both density and thermal conductivity, although its mechanical performance is very limited, due to its higher water content. Nevertheless, this last formulation could potentially serve as a viable starting point for the development of a sustainable cement-free construction material for the insulation of the building envelope. Further studies in this direction are currently underway.

The Emilia 2012 earthquake highlighted the high vulnerability of historical masonry spires, at the top of bell towers. Indeed almost half of the spires, in the area hit by the seismic event, show the loss of the top. The observed collapse mechanism consists in sliding of the spire top and in the resulting overturning. Once the emergency phase has passed, it is now a duty to learn from this traumatic experience and to provide new tools for the prevention of the destructive effects of future earthquakes. In this perspective, a geodatabase was designed, using the ArcGIS Pro software, for monitoring the vulnerabilities of the surveyed spires. Indeed, as we learn from the study of the effects of past earthquakes, seismic damages are recurrent for each building typology and therefore they can be predictable and avoidable. For example, by statistically elaborating the data of the designed database, a correlation arose between the levels of damage of the spires and their type of masonry arrangement. Indeed four different masonry typologies have been distinguished. The work then focuses on three damaged spires of churches belfries, proposing three consolidation hypotheses to prevent the future loss of the rebuilt top part of the spire. The structural analyses, performed with Abaqus CAE and detailed in a different work, showed that the same intervention produces different results on the different case studies: a demonstration that there is not an "absolute" best solution, but an intervention suitable for each case. [ABSTRACT FROM AUTHOR]

This work focuses on the mechanical characterization of the inorganic matrix used for Fiber-Reinforced Cementitious Matrix (FRCM) composites, nowadays widely used to retrofit existing reinforced concrete and masonry structures. While several works in technical literature investigate the experimental behavior of the whole FRCM composite, few information are available on the mechanical characterization of the mortar, which contains polymers and synthetic fibers in its admixture. However, the knowledge of its behavior in tension, especially after crack formation, is an important feature for the calibration of constitutive models to be adopted in the study of structural elements strengthened with FRCM. To this aim, an experimental program was performed on mortar specimens characterized by different shapes and dimensions, tested under direct tension or three-point-bending. From the performed tests, it was possible to characterize inorganic matrix behavior both in the uncracked stage, through the determination of the elastic parameters (elastic modulus and Poisson's coefficient), and in the cracked stage. The use of digital image correlation (DIC) technique also allowed the study of the evolution of crack propagation in the specimens. Lastly, a correlation factor between axial and flexural tensile strength is proposed, for both design and numerical modelling purposes. [ABSTRACT FROM AUTHOR]

The paper aims to analyse the effects of pretreatment thermal cycles on both mechanical and fracture parameters of the red Verona marble, which is a natural stone of sedimentary formation. The effects of the thermal pretreatment, consisting of freeze/thaw cycles and simulating the atmospheric ageing on the material, are evaluated in terms of changes of the aforementioned parameters. Note that a wide variety of both specimen types and methods to determine mode I plain strain fracture toughness of rocks are available in the literature. The two-parameter model originally proposed for plain concrete is herein adopted. Such a method, based on the experimental data obtained from three-point bending tests on single edge-notched specimens, is able to take into account the slow nonlinear crack growth occurring before the peak load, typical of quasibrittle materials, and presents the advantages of easy specimens preparation and simple test configuration. [ABSTRACT FROM AUTHOR]

Little is known about how the methane source inventory and sinks have evolved over recent centuries. New and detailed records of methane mixing ratio and isotopic composition (12CH4, 13CH4 and 14CH4) from analyses of air trapped in polar ice and firn can enhance this knowledge. We use existing bottom-up constructions of the source history, including "EDGAR"-based constructions, as inputs to a model of the evolving global budget for methane and for its carbon isotope composition through the 20th century. By matching such budgets to atmospheric data, we examine the constraints imposed by isotope information on those budget evolutions. Reconciling both 12CH4 and 13CH4 budgets with EDGAR-based source histories requires a combination of: a greater proportion of emissions from biomass burning and/or of fossil methane than EDGAR constructions suggest; a greater contribution from natural such emissions than is commonly supposed; and/or a significant role for active chlorine or other highly-fractionating tropospheric sink as has been independently proposed. Examining a companion budget evolution for 14CH4 exposes uncertainties in inferring the fossil-methane source from atmospheric 14CH4 data. Specifically, methane evolution during the nuclear era is sensitive to the cycling dynamics of "bomb 14C" (originating from atmospheric weapons tests) through the biosphere. In addition, since ca. 1970, direct production and release of 14CH4 from nuclear-power facilities is influential but poorly quantified. Atmospheric 14CH4 determinations in the nuclear era have the potential to better characterize both biospheric carbon cycling, from photosynthesis to methane synthesis, and the nuclear-power source. [ABSTRACT FROM AUTHOR]

Recently Keppler et al. (2006) discovered a surprising new source of methane -- terrestrial plants under aerobic conditions, with an estimated global production of 62-236 Tg yr-1 by an unknown mechanism. This is ∼10-50% of the annual total of methane entering the modern atmosphere and ∼30-100% of annual methane entering 5 the pre-industrial (0 to 1700 AD) atmosphere. Here we test this reported global production of methane from plants against ice core records of atmospheric methane concentration (CH4) and stable carbon isotope ratios (δ13CH4) over the last 2000 years. Our top-down approach determines that global plant emissions must be much lower than proposed by Keppler et al. (2006) during the last 2000 years and are likely to lie in the range 0-46 Tg yr-1. [ABSTRACT FROM AUTHOR]

Little is known about how the methane source inventory and sinks have evolved over recent centuries. New and detailed records of methane mixing ratio and isotopic composition (12CH4, 13CH4 and 14CH4) from analyses of air trapped in polar ice and firn can enhance this knowledge. We use existing bottom-up constructions of the source history, including "EDGAR"-based constructions, to assemble a model of the evolving global budget for methane and for its carbon isotope composition through the 20th century. By matching such budgets to atmospheric data, we examine the constraints imposed by isotope information on those budget evolutions. Balancing both 12CH4 and 13CH4 budgets requires participation by a highly-fractionating atmospheric sink such as active chlorine (removing at least 10 Tg yr-1), which has been proposed independently. Examining a companion budget evolution for 14CH4 exposes uncertainties in inferring the fossil-methane source from atmospheric 14CH4 data. Specifically, methane evolution during the nuclear era is sensitive to the cycling dynamics of "bomb 14C" (originating from atmospheric weapons tests) through the biosphere. In addition, since ca 1970, direct production and release of 14CH4 from nuclear-power facilities is influential but poorly quantified. Atmospheric 14CH4 determinations in the nuclear era have the potential to better characterize biospheric carbon cycling and to better quantify the ill-determined nuclear-power source. [ABSTRACT FROM AUTHOR]

The stable isotopic composition of soil water is controlled by precipitation inputs, antecedent conditions, and evaporative losses. Because transpiration does not fractionate soil water isotopes, the relative proportions of evaporation and transpiration can be estimated using a simple isotopic mass balance approach. At our site in the shortgrass steppe in semi-arid northeastern Colorado, δ18O values of soil water were almost always more enriched than those of precipitation inputs, owing to evaporative losses. The proportion of water lost by evaporation (E/ET) during the growing season ranged from nil to about 40% (to >90% in the dormant season), and was related to the timing of precipitation inputs. The sum of transpiration plus evaporation losses estimated by isotopic mass balance were similar to actual evapotranspiration measured from a nearby Bowen ratio system. We also investigated the evapotranspiration response of this mixed C3/C4 grassland to doubled atmospheric [CO2] using Open-Top Chambers (OTC). Elevated atmospheric [CO2] led to increased soil-water conservation via reduced stomatal conductance, despite greater biomass growth. We used a non-invasive method to measure the δ18O of soil CO2 as a proxy for soil water, after establishing a strong relationship between δ18O of soil CO2 from non-chambered control (NC) plots and δ18O of soil–water from an adjacent area of native grassland. Soil–CO2 δ18O values showed significant treatment effects, particularly during a dry summer: values in ambient chambers (AC) were more enriched than in NC and elevated chamber (EC) plots. During the dry growing season of 2000, transpiration from the EC treatment was higher than from AC and lower than from NC treatments, but during 2001, transpiration was similar on all three treatments. Slightly higher evaporation rates from AC than either EC or NC treatments in 2000 may have resulted from increased convection across the soil surface from the OTC blowers, combined with lower biomass and litter cover on the AC treatment. Transpiration-use efficiency, or the amount of above-ground biomass produced per mm water transpired, was always greatest on EC and lowest on NC treatments. [ABSTRACT FROM AUTHOR]

The stable isotopic composition of soil water is controlled by precipitation inputs, antecedent conditions, and evaporative losses. Because transpiration does not fractionate soil water isotopes, the relative proportions of evaporation and transpiration can be estimated using a simple isotopic mass balance approach. At our site in the shortgrass steppe in semi-arid northeastern Colorado, δ18O values of soil water were almost always more enriched than those of precipitation inputs, owing to evaporative losses. The proportion of water lost by evaporation (E/ET) during the growing season ranged from nil to about 40% (to >90% in the dormant season), and was related to the timing of precipitation inputs. The sum of transpiration plus evaporation losses estimated by isotopic mass balance were similar to actual evapotranspiration measured from a nearby Bowen ratio system. We also investigated the evapotranspiration response of this mixed C3/C4 grassland to doubled atmospheric [CO2] using Open-Top Chambers (OTC). Elevated atmospheric [CO2] led to increased soil-water conservation via reduced stomatal conductance, despite greater biomass growth. We used a non-invasive method to measure the δ18O of soil CO2 as a proxy for soil water, after establishing a strong relationship between δ18O of soil CO2 from non-chambered control (NC) plots and δ18O of soil–water from an adjacent area of native grassland. Soil–CO2 δ18O values showed significant treatment effects, particularly during a dry summer: values in ambient chambers (AC) were more enriched than in NC and elevated chamber (EC) plots. During the dry growing season of 2000, transpiration from the EC treatment was higher than from AC and lower than from NC treatments, but during 2001, transpiration was similar on all three treatments. Slightly higher evaporation rates from AC than either EC or NC treatments in 2000 may have resulted from increased convection across the soil surface from the OTC blowers, combined with lower biomass and litter cover on the AC treatment. Transpiration-use efficiency, or the amount of above-ground biomass produced per mm water transpired, was always greatest on EC and lowest on NC treatments. [ABSTRACT FROM AUTHOR]

Sin resumen

Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after therapy exhibit high POSTN expression levels and high numbers of TTR macrophages. POSTN polarizes human macrophages toward a TTR phenotype and promotes resistance to targeted therapy in a melanoma mouse model, which is associated with a phenotype change in intratumoral macrophages. Finally, polarized TTR macrophages directly protect human melanoma cells from MEKi-induced killing via CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages may offer a strategy to overcome resistance to targeted therapy in melanoma., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Toxic gain-of-function mutations in superoxide dismutase 1 (SOD1) contribute to approximately 2%-3% of all amyotrophic lateral sclerosis (ALS) cases. Artificial microRNAs (amiRs) delivered by adeno-associated virus (AAV) have been proposed as a potential treatment option to silence SOD1 expression and mitigate disease progression. Primary microRNA (pri-miRNA) scaffolds are used in amiRs to shuttle a hairpin RNA into the endogenous miRNA pathway, but it is unclear whether different primary miRNA (pri-miRNA) scaffolds impact the potency and safety profile of the expressed amiR in vivo . In our process to develop an AAV amiR targeting SOD1, we performed a preclinical characterization of two pri-miRNA scaffolds, miR155 and miR30a, sharing the same guide strand sequence. We report that, while the miR155-based vector, compared with the miR30a-based vector, leads to a higher level of the amiR and more robust suppression of SOD1 in vitro and in vivo , it also presents significantly greater risks for CNS-related toxicities in vivo . Despite miR30a-based vector showing relatively lower potency, it can significantly delay the development of ALS-like phenotypes in SOD1-G93A mice and increase survival in a dose-dependent manner. These data highlight the importance of scaffold selection in the pursuit of highly efficacious and safe amiRs for RNA interference gene therapy., Competing Interests: M.H. is a paid advisor from Charter Preclinical Services. All other authors are paid employees at Biogen., (© 2023 The Author(s).)

CRISPR-based gene editing technology represents a promising approach to deliver therapies for inherited disorders, including amyotrophic lateral sclerosis (ALS). Toxic gain-of-function superoxide dismutase 1 (SOD1) mutations are responsible for ~20% of familial ALS cases. Thus, current clinical strategies to treat SOD1-ALS are designed to lower SOD1 levels. Here, we utilized AAV-PHP.B variants to deliver CRISPR-Cas9 guide RNAs designed to disrupt the human SOD1 (huSOD1) transgene in SOD1 G93A mice. A one-time intracerebroventricular injection of AAV.PHP.B-huSOD1-sgRNA into neonatal H11 Cas9 SOD1 G93A mice caused robust and sustained mutant huSOD1 protein reduction in the cortex and spinal cord, and restored motor function. Neonatal treatment also reduced spinal motor neuron loss, denervation at neuromuscular junction (NMJ) and muscle atrophy, diminished axonal damage and preserved compound muscle action potential throughout the lifespan of treated mice. SOD1 G93A treated mice achieved significant disease-free survival, extending lifespan by more than 110 days. Importantly, a one-time intrathecal or intravenous injection of AAV.PHP.eB-huSOD1-sgRNA in adult H11 Cas9 SOD1 G93A mice, immediately before symptom onset, also extended lifespan by at least 170 days. We observed substantial protection against disease progression, demonstrating the utility of our CRISPR editing preclinical approach for target evaluation. Our approach uncovered key parameters (e.g., AAV capsid, Cas9 expression) that resulted in improved efficacy compared to similar approaches and can also serve to accelerate drug target validation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We introduce Metis, a new plugin for the Perseus software aimed at analyzing quantitative multi-omics data based on metabolic pathways. Data from different omics types are connected through reactions of a genome-scale metabolic-pathway reconstruction. Metabolite concentrations connect through the reactants, while transcript, protein, and protein post-translational modification (PTM) data are associated through the enzymes catalyzing the reactions. Supported experimental designs include static comparative studies and time-series data. As an example for the latter, we combine circadian mouse liver multi-omics data and study the contribution of cycles of phosphoproteome and metabolome to enzyme activity regulation. Our analysis resulted in 52 pairs of cycling phosphosites and metabolites connected through a reaction. The time lags between phosphorylation and metabolite peak show non-uniform behavior, indicating a major contribution of phosphorylation in the modulation of enzymatic activity., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Colors enable interaction and communication between living species in a myriad of biological and artificial environments. While living organisms feature low-power mechanisms to dynamically control color in soft tissues, man-made color-changing devices remain predominantly rigid and energy intensive. Here, architectured composites that display striking color changes when stretched in selective directions under ambient light with minimum power input are reported. The orientation-dependent color change results from the rotation of reflective coated platelets that are embedded in a soft polymer matrix and pre-aligned in a well-defined architecture. The light reflected by the platelets generates structural color defined by the oxide coating on the platelet surface. By magnetically programming the initial orientation and spatial distribution of selected platelets within the soft matrix, composites with strain-modulated color-changing effects that cannot be achieved using state-of-the-art technologies are created. The proposed concept of strain-induced architectured color can be harnessed to develop low-power smart stretchable displays, tactile synthetic skins, and autonomous soft robotic devices that undergo fast and reversible color changes through the mechano-optic coupling programmed within their soft composite architecture., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Neurocognitive tests offer objective and reliable assessment of patients' status and progress. However, there is no consensus on how to use neurocognitive assessment in sleep disorder research. An effective use of neurocognitive assessment must be based on standardized practices and have a firm theoretic basis. The aim of this review is to offer an overview of how different tests have been used in the field, mapping each test onto a corresponding cognitive domain and propose how to move forward with a suggested cognitive battery of tests covering all major cognitive domains., Competing Interests: Disclosure The authors have nothing to disclose. The work of the authors is sponsored in part by the Sleep Revolution, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 965417 and by NordForsk (NordSleep project 90458-06111) via the Icelandic Centre for Research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Perseus software provides a comprehensive framework for the statistical analysis of large-scale quantitative proteomics data, also in combination with other omics dimensions. Rapid developments in proteomics technology and the ever-growing diversity of biological studies increasingly require the flexibility to incorporate computational methods designed by the user. Here, we present the new functionality of Perseus to integrate self-made plugins written in C#, R, or Python. The user-written codes will be fully integrated into the Perseus data analysis workflow as custom activities. This also makes language-specific R and Python libraries from CRAN (cran.r-project.org), Bioconductor (bioconductor.org), PyPI (pypi.org), and Anaconda (anaconda.org) accessible in Perseus. The different available approaches are explained in detail in this article. To facilitate the distribution of user-developed plugins among users, we have created a plugin repository for community sharing and filled it with the examples provided in this article and a collection of already existing and more extensive plugins. © 2020 The Authors. Basic Protocol 1: Basic steps for R plugins Support Protocol 1: R plugins with additional arguments Basic Protocol 2: Basic steps for python plugins Support Protocol 2: Python plugins with additional arguments Basic Protocol 3: Basic steps and construction of C# plugins Basic Protocol 4: Basic steps of construction and connection for R plugins with C# interface Support Protocol 4: Advanced example of R Plugin with C# interface: UMAP Basic Protocol 5: Basic steps of construction and connection for python plugins with C# interface Support Protocol 5: Advanced example of python plugin with C# interface: UMAP Support Protocol 6: A basic workflow for the analysis of label-free quantification proteomics data using perseus., (© 2020 The Authors.)

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms., (© 2019 Wiley Periodicals, Inc.)

The primary cause of injury-related death for the elders is represented by falls. The scientific community devoted them particular attention, since injuries can be limited by an early detection of the event. The solution proposed in this paper is based on a combined One-Class SVM (OCSVM) and template-matching classifier that discriminate human falls from nonfalls in a semisupervised framework. Acoustic signals are captured by means of a Floor Acoustic Sensor; then Mel-Frequency Cepstral Coefficients and Gaussian Mean Supervectors (GMSs) are extracted for the fall/nonfall discrimination. Here we propose a single-sensor two-stage user-aided approach: in the first stage, the OCSVM detects abnormal acoustic events. In the second, the template-matching classifier produces the final decision exploiting a set of template GMSs related to the events marked as false positives by the user. The performance of the algorithm has been evaluated on a corpus containing human falls and nonfall sounds. Compared to the OCSVM only approach, the proposed algorithm improves the performance by 10.14% in clean conditions and 4.84% in noisy conditions. Compared to Popescu and Mahnot (2009) the performance improvement is 19.96% in clean conditions and 8.08% in noisy conditions.