Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle ...Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.
•Gastric cancer management will benefit from knowledge of its molecular features.•Powerful information is obtained from complementary large-scale molecular studies.•Cost-effective protein and mRNA ...expression methods allow for GC classification.•Sequencing analysis of specific GC gene panels will complement expression studies.
Gastric Cancer (GC) is a complex and heterogeneous disease, which represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still a leading cause of cancer-related death. Over the last decade, several clinical trials have tested novel agents for advanced GC with mostly disappointing results. Heterogeneity, the absence of molecular selection in clinical trials and powerless predictive biomarkers may be potential explanations. Different molecular classification proposals for GC based on the genetic, epigenetic, and molecular signatures have been published. Molecular characterization of GC may offer new tools for more effective therapeutic strategies, such as the development of therapies for specifically well-defined sets of patients as well as the use of new clinical trial designs, which will ultimately lead to an improvement of medical management of this disease. However, the possibilities of implementation of GC molecular classifications on daily practice and their therapeutic implications remain challenging to date. In this review, we will describe and compare these GC molecular classifications, focusing on their main characteristics as the basis for their potential therapeutic implications and strategies for their clinical application.
Key Message: A better understanding of gastric cancer molecular characteristics may lead to further improvements in treatment and outcomes for patients with the disease.
There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes ...and progression of gastric preneoplastic lesions.
This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression.
The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains.
H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.
Nanostructured Nb-C thin films were prepared by direct current magnetron sputtering (DC-MS) and high-power impulse magnetron sputtering (HiPIMS). The films were characterized in depth by X-ray ...diffraction (XRD), grazing incidence X-ray diffraction, scanning electron microscopy, atomic force microscopy, electron probe microanalysis, and Raman spectroscopy. The mechanical properties were measured by nanoindentation, and the tribological properties were measured by pin-on-disk tests in ambient air. The wear tracks and ball scars were analyzed by Raman spectroscopy to elucidate the tribochemical reactions that occurred at the contact area and to determine the wear mechanism for each specimen type. The thermal stability of the coatings was studied up to 1000 °C using Raman spectroscopy and XRD. The samples prepared by DC-MS were very dense, and the phase composition changed from purely nanocrystalline (Nb2C and NbC) to a mixture of NbC crystals embedded in an amorphous carbon-based matrix (NbC/a-C(:H)). However, the samples prepared by HiPIMS developed a marked columnar morphology with a NbC/a-C(:H) nanocomposite structure. The hardness values ranged from 11 to 20 GPa depending on the deposition technique and the amount of the soft a-C(:H) phase present in the sample. The tribological properties of all the coatings were remarkably good when the carbon content was approximately 50 at.%. The formation of a lubricating sp2-rich C tribofilm between the ball and coating during the pin-on-disk tests was observed by Raman spectroscopy. The tribofilm formed preferentially on the samples prepared by HiPIMS, which had higher C contents. At 750 °C, the degradation of the NbC phases resulted in the formation of an additional a-C phase and niobium oxides.
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•Nb-C coatings with variable contents of NbC and a-C were prepared by DC and HiPIMS.•HiPIMS samples presented a much more columnar structure compared DC samples.•A lubricant C tribofilm is formed for samples with high C content (>50 at.%).•DC samples presented a better thermal stability compared with HiPIMS samples.
The Main Bending Recombination Dipole (MBRD), or D2, is one of the magnets foreseen by the High-Luminosity upgrade of the Large Hadron Collider (LHC). D2 features a double aperture, Nb-Ti, cos ...<inline-formula><tex-math notation="LaTeX">\theta</tex-math></inline-formula> dipole, with a central field of 4.5 T for a length of 7.78 m, hence with an integrated magnetic field of 35 T<inline-formula><tex-math notation="LaTeX">\cdot</tex-math></inline-formula> m, in a 105 mm bore. The project includes the fabrication of a 1.6 m long model, a full-length prototype and six series magnets, two of which are spare. Till now, the short model and the prototype have been successfully constructed and tested in 2020 and 2023, while the series magnets are presently under manufacturing and the warm magnetic measurements of the first built magnet were performed at the end of July 2023. This contribution will report the final field quality analysis of the prototype and the preliminary one of the series magnets, including results of the first measurements at room temperature (RT), a comparison with the ROXIE simulations and the expected field quality at operating conditions.
•Nb-C coatings have been prepared by DC and HiPIMS.•A coating densification by changing from DC to HiPIMS was not observed.•Higher amount and clustering of a-C:H is formed in HiPIMS vs.DC at ...comparative C at.%•Good tribological properties are obtained for samples with high C content (>50 at.%)
Nanostructured NbC thin films with variable contents of Nb and C were prepared by direct current (DC) magnetron sputtering, and for the first time, via high power impulse magnetron sputtering (HiPIMS) searching for an improvement in the tribological properties. X-ray diffraction shows that increasing the carbon incorporation, the crystalline composition evolves from Nb2C to NbC phase. Further carbon enrichment leads to a nanocomposite structure formed by small NbC crystals (8–14 nm) dispersed in a-C matrix. The friction coefficient varied from high friction (0.8) to low friction (0.25) and the hardness values between 20 and 11 GPa depending on the film composition. A densification of the coatings by changing the methodology from DC to HiPIMS was not observed.
The aim of the current study was to evaluate the factor structure of the CArtes- Modèles Individuels de Relations (CA-MIR), a self-report questionnaire designed to tap into the relational strategies ...of adults that was developed by a French-speaking research group coordinated by Blaise Pierrehumbert. The CA-MIR's particular merit lies in the richness and complexity of the theoretical model underpinning it. However, to date, this model has only been partially reproduced in studies using exploratory analysis and has never been tested via confirmatory factor analysis (CFA).
We thus conducted CFA on data collected from a sample of 979 subjects, recruited using a snowball sampling method during the spring and fall of 2005. To assess if some item multidimensionality was present, we estimated both the independent clusters model (ICM-CFA) and a model in which some zero loading restrictions were removed.
The results supported the originally proposed structure of the CA-MIR; the large majority of items were good indicators of the expected latent dimensions and only few items showed relevant secondary loadings or loaded in an unexpected factor. The instrument adequately differentiates the three attachment styles, taking into account both past and present experiences of attachment relationships, and providing a rich and complex assessment of multiple features of attachment. In terms of internal consistency, alpha values were satisfactory and comparable to those found in the original Swiss validation study.
Our results are of key importance for both research and clinical work, given the lack of valid and easy-to-administer tools for evaluating adult attachment.
The quest for advancing science and technology continues with the Future Circular Collider (FCC), which requires 16 T bending dipoles to be installed along its 100 km tunnel to achieve a ...center-of-mass energy of 100 TeV, in its hadron-hadron version. The promising NbFormula OmittedSn technology for superconducting magnets presents a potential solution for large-scale production. In line with this, the European strategy for particle physics has urged for increased efforts in High Field Magnet R&D, specifically in constructing demonstrators for NbFormula OmittedSn technology. To address this call, the Istituto Nazionale di Fisica Nucleare (INFN) and CERN entered into an agreement to build a 1.5 m long cos-theta dipole in NbFormula OmittedSn, called Falcon Dipole (The Future Accelerator post-LHC Cos-theta Optimized NbFormula OmittedSn Dipole). The project aims to consolidate the fabrication process for NbFormula OmittedSn superconducting dipoles in the 12–14 T range, engaging industry partners in the initial stages of the R&D phase. This article provides a recall of the magnet design features and highlights the progress made in the development activities. Critical processes like the reaction treatment and the impregnation are discussed, with an emphasis on the test outcomes and the challenges faced. By taking these into account, plans for the production of the coils for the final configuration can be effectively formulated.
The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The ...system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque formation, mutations in its components affect atherosclerosis severity. Here we used Taqman low-density arrays and immunoblotting to study mRNA and protein expression of GAS6, ProS and the TAM receptors in human carotid arteries with different degrees of atherosclerosis. The results show a clear down-regulation of the expression of AXL in atheroma plaques with respect to normal carotids that is matched by decreased abundance of AXL in protein extracts detected by immunoblotting. A similar decrease was observed in PROS1 mRNA expression in atherosclerotic carotids compared to the normal ones, but in this case protein S (ProS) was clearly increased in protein extracts of carotid arteries with increasing grade of atherosclerosis, suggesting that ProS is carried into the plaque. MERTK was also increased in atherosclerotic carotid arteries with respect to the normal ones, suggesting that the ProS-MERTK axis is functional in advanced human atherosclerotic plaques. MERTK was expressed in macrophages, frequently in association with ProS, while ProS was abundant also in the necrotic core. Our data suggest that the ProS-MERTK ligand-receptor pair was active in advanced stages of atherosclerosis, while AXL signalling is probably down-regulated.
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