Behaviour of a Large Anchored Basement in Dense Sands and Gravels

Prior to the excavation of half a million cubic meters of dense gravelly material within the city centre of Milan, a 24 to 27m long diaphragm wall was built to provide a 17m retained height to a four-level basement. Temporary support was offered by two to four rows of ground anchors with the exception of a portion adjacent to an existing multi-level cark park where a post-tensioned capping beam was installed to protect the car park and prevent it from being subject to sway. Other design challenges were posed by the proximity of a buried channel and of an urban rail tunnel. An extensive monitoring system was set up including inclinometers, load cells and topographical survey points to reveal lateral movements in the order of 10mm or less, negligible variation of anchor loads as the excavation progressed and heave behind the wall. In response to a general lack of case histories and design guidance on deep excavations in dense coarse material, especially in the region, a backanalysis of diaphragm wall monitoring data was carried out and its main results are commented on in the present paper. Lateral movements are best reproduced with pseudo-FE or full FE software if a soil stiffness compatible with the relevant shear strain level is adopted

Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis

Dysfunction of mitochondrial respiration is an increasingly recognized cause of isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes mitochondrial translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs∗8) frameshift and a paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for the latter change. In both humans and yeast, MTO1 increases the accuracy and efficiency of mtDNA translation by catalyzing the 5-carboxymethylaminomethylation of the wobble uridine base in three mitochondrial tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably combined reduction in mtDNA-dependent respiratory chain activities. Reduced respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA. Conversely, defective respiration of a yeast mto1Δ strain failed to be corrected by an Mto1Pro622∗ variant, equivalent to human MTO1Arg620Lysfs∗8, whereas incomplete correction was achieved by an Mto1Ala431Thr variant, corresponding to human MTO1Ala428Thr. The respiratory yeast phenotype was dramatically worsened in stress conditions and in the presence of a paromomycin-resistant (PR) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation was impaired in the mutant yeast strains

Primordial non-Gaussianity with Angular correlation function: Integral constraint and validation for DES

Local primordial non-Gaussianity (PNG) is a promising observable of the underlying physics of inflation, characterised by $f_{\rm NL}^{\rm loc}$. We present the methodology to measure $f_{\rm NL}^{\rm loc}$ from the Dark Energy Survey (DES) data using the 2-point angular correlation function (ACF) with scale-dependent bias. One of the focuses of the work is the integral constraint. This condition appears when estimating the mean number density of galaxies from the data and is key in obtaining unbiased $f_{\rm NL}^{\rm loc}$ constraints. The methods are analysed for two types of simulations: $\sim 246$ GOLIAT-PNG N-body small area simulations with $f_{\rm NL}$ equal to -100 and 100, and 1952 Gaussian ICE-COLA mocks with $f_{\rm NL}=0$ that follow the DES angular and redshift distribution. We use the ensemble of GOLIAT-PNG mocks to show the importance of the integral constraint when measuring PNG, where we recover the fiducial values of $f_{\rm NL}$ within the $1\sigma$ when including the integral constraint. In contrast, we found a bias of $\Delta f_{\rm NL}\sim 100$ when not including it. For a DES-like scenario, we forecast a bias of $\Delta f_{\rm NL} \sim 23$, equivalent to $1.8\sigma$, when not using the IC for a fiducial value of $f_{\rm NL}=100$. We use the ICE-COLA mocks to validate our analysis in a realistic DES-like setup finding it robust to different analysis choices: best-fit estimator, the effect of IC, BAO damping, covariance, and scale choices. We forecast a measurement of $f_{\rm NL}$ within $\sigma(f_{\rm NL})=31$ when using the DES-Y3 BAO sample, with the ACF in the $1\ {\rm deg}<\theta<20\ {\rm deg}$ range.Comment: Version after MNRAS reviewer comments. Improved discussion in Section 7. 16 pages, 11 figure

AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis

Inter-laboratory mass spectrometry dataset based on passive sampling of drinking water for non-target analysis

Non-target analysis (NTA) employing high-resolution mass spectrometry is a commonly applied approach for the detection of novel chemicals of emerging concern in complex environmental samples. NTA typically results in large and information-rich datasets that require computer aided (ideally automated) strategies for their processing and interpretation. Such strategies do however raise the challenge of reproducibility between and within different processing workflows. An effective strategy to mitigate such problems is the implementation of inter-laboratory studies (ILS) with the aim to evaluate different workflows and agree on harmonized/standardized quality control procedures. Here we present the data generated during such an ILS. This study was organized through the Norman Network and included 21 participants from 11 countries. A set of samples based on the passive sampling of drinking water pre and post treatment was shipped to all the participating laboratories for analysis, using one pre-defined method and one locally (i.e. in-house) developed method. The data generated represents a valuable resource (i.e. benchmark) for future developments of algorithms and workflows for NTA experiments

Constraints on dark matter to dark radiation conversion in the late universe with DES-Y1 and external data

84siWe study a class of decaying dark matter models as a possible resolution to the observed discrepancies between early- and late-time probes of the universe. This class of models, dubbed DDM, characterizes the evolution of comoving dark matter density with two extra parameters. We investigate how DDM affects key cosmological observables such as the CMB temperature and matter power spectra. Combining 3x2pt data from Year 1 of the Dark Energy Survey,Planck-2018 CMB temperature and polarization data, Supernova (SN) Type Ia data from Pantheon, and BAO data from BOSS DR12, MGS and 6dFGS, we place new constraints on the amount of dark matter that has decayed and the rate with which it converts to dark radiation. The fraction of the decayed dark matter in units of the current amount of dark matter, $zeta$, is constrained at 68% confidence level to be <0.32 for DES-Y1 3x2pt data, <0.030 for CMB+SN+BAO data, and <0.037 for the combined dataset. The probability that the DES and CMB+SN+BAO datasets are concordant increases from 4% for the $Lambda$CDM model to 8% (less tension) for DDM. Moreover, tension in $S_8=sigma_8sqrt{Omega_m/0.3}$ between DES-Y1 3x2pt and CMB+SN+BAO is reduced from 2.3$sigma$ to 1.9$sigma$. We find no reduction in the Hubble tension when the combined data is compared to distance-ladder measurements in the DDM model. The maximum-posterior goodness-of-fit statistics of DDM and $Lambda$CDM are comparable, indicating no preference for the DDM cosmology over $Lambda$CDM....partially_openopenChen, Angela; Huterer, Dragan; Lee, Sujeong; Ferté, Agnès; Weaverdyck, Noah; Alonso Alves, Otavio; Leonard, C. Danielle; MacCrann, Niall; Raveri, Marco; Porredon, Anna; Di Valentino, Eleonora; Muir, Jessica; Lemos, Pablo; Liddle, Andrew; Blazek, Jonathan; Campos, Andresa; Cawthon, Ross; Choi, Ami; Dodelson, Scott; Elvin-Poole, Jack; Gruen, Daniel; Ross, Ashley; Secco, Lucas F.; Sevilla, Ignacio; Sheldon, Erin; Troxel, Michael A.; Zuntz, Joe; Abbott, Tim; Aguena, Michel; Allam, Sahar; Annis, James; Avila, Santiago; Bertin, Emmanuel; Bhargava, Sunayana; Bridle, Sarah; Brooks, David; Carnero Rosell, Aurelio; Carrasco Kind, Matias; Carretero, Jorge; Costanzi, Matteo; Crocce, Martin; da Costa, Luiz; Elidaiana da Silva Pereira, Maria; Davis, Tamara; Doel, Peter; Eifler, Tim; Ferrero, Ismael; Fosalba, Pablo; Frieman, Josh; Garcia-Bellido, Juan; Gaztanaga, Enrique; Gerdes, David; Gruendl, Robert; Gschwend, Julia; Gutierrez, Gaston; Hinton, Samuel; Hollowood, Devon L.; Honscheid, Klaus; Hoyle, Ben; James, David; Jarvis, Mike; Kuehn, Kyler; Lahav, Ofer; Maia, Marcio; Marshall, Jennifer; Menanteau, Felipe; Miquel, Ramon; Morgan, Robert; Palmese, Antonella; Paz-Chinchon, Francisco; Plazas Malagón, Andrés; Roodman, Aaron; Sanchez, Eusebio; Scarpine, Vic; Schubnell, Michael; Serrano, Santiago; Smith, Mathew; Suchyta, Eric; Tarle, Gregory; Thomas, Daniel; To, Chun-Hao; Varga, Tamas Norbert; Weller, Jochen; Wilkinson, ReeseChen, Angela; Huterer, Dragan; Lee, Sujeong; Ferté, Agnès; Weaverdyck, Noah; Alonso Alves, Otavio; Leonard, C. Danielle; Maccrann, Niall; Raveri, Marco; Porredon, Anna; Di Valentino, Eleonora; Muir, Jessica; Lemos, Pablo; Liddle, Andrew; Blazek, Jonathan; Campos, Andresa; Cawthon, Ross; Choi, Ami; Dodelson, Scott; Elvin-Poole, Jack; Gruen, Daniel; Ross, Ashley; Secco, Lucas F.; Sevilla, Ignacio; Sheldon, Erin; Troxel, Michael A.; Zuntz, Joe; Abbott, Tim; Aguena, Michel; Allam, Sahar; Annis, James; Avila, Santiago; Bertin, Emmanuel; Bhargava, Sunayana; Bridle, Sarah; Brooks, David; Carnero Rosell, Aurelio; Carrasco Kind, Matias; Carretero, Jorge; Costanzi, Matteo; Crocce, Martin; da Costa, Luiz; Elidaiana da Silva Pereira, Maria; Davis, Tamara; Doel, Peter; Eifler, Tim; Ferrero, Ismael; Fosalba, Pablo; Frieman, Josh; Garcia-Bellido, Juan; Gaztanaga, Enrique; Gerdes, David; Gruendl, Robert; Gschwend, Julia; Gutierrez, Gaston; Hinton, Samuel; Hollowood, Devon L.; Honscheid, Klaus; Hoyle, Ben; James, David; Jarvis, Mike; Kuehn, Kyler; Lahav, Ofer; Maia, Marcio; Marshall, Jennifer; Menanteau, Felipe; Miquel, Ramon; Morgan, Robert; Palmese, Antonella; Paz-Chinchon, Francisco; Plazas Malagón, Andrés; Roodman, Aaron; Sanchez, Eusebio; Scarpine, Vic; Schubnell, Michael; Serrano, Santiago; Smith, Mathew; Suchyta, Eric; Tarle, Gregory; Thomas, Daniel; Chun-Hao, To; Varga, Tamas Norbert; Weller, Jochen; Wilkinson, Rees

The sustainable materials roadmap

Over the past 150 years, our ability to produce and transform engineered materials has been responsible for our current high standards of living, especially in developed economies. However, we must carefully think of the effects our addiction to creating and using materials at this fast rate will have on the future generations. The way we currently make and use materials detrimentally affects the planet Earth, creating many severe environmental problems. It affects the next generations by putting in danger the future of the economy, energy, and climate. We are at the point where something must drastically change, and it must change now. We must create more sustainable materials alternatives using natural raw materials and inspiration from nature while making sure not to deplete important resources, i.e. in competition with the food chain supply. We must use less materials, eliminate the use of toxic materials and create a circular materials economy where reuse and recycle are priorities. We must develop sustainable methods for materials recycling and encourage design for disassembly. We must look across the whole materials life cycle from raw resources till end of life and apply thorough life cycle assessments (LCAs) based on reliable and relevant data to quantify sustainability. We need to seriously start thinking of where our future materials will come from and how could we track them, given that we are confronted with resource scarcity and geographical constrains. This is particularly important for the development of new and sustainable energy technologies, key to our transition to net zero. Currently 'critical materials' are central components of sustainable energy systems because they are the best performing. A few examples include the permanent magnets based on rare earth metals (Dy, Nd, Pr) used in wind turbines, Li and Co in Li-ion batteries, Pt and Ir in fuel cells and electrolysers, Si in solar cells just to mention a few. These materials are classified as 'critical' by the European Union and Department of Energy. Except in sustainable energy, materials are also key components in packaging, construction, and textile industry along with many other industrial sectors. This roadmap authored by prominent researchers working across disciplines in the very important field of sustainable materials is intended to highlight the outstanding issues that must be addressed and provide an insight into the pathways towards solving them adopted by the sustainable materials community. In compiling this roadmap, we hope to aid the development of the wider sustainable materials research community, providing a guide for academia, industry, government, and funding agencies in this critically important and rapidly developing research space which is key to future sustainability.journal articl

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox. epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-.network.com/nds/SLE/)

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe