A central tenet in the theory of quantum phase transitions (QPTs) is that a nonanalyticity in a ground-state energy implies a QPT. Here we report on a finding that challenges this assertion. As a ...case study we take a phase diagram of a one-dimensional band insulator with spin-orbit coupled electrons, supporting trivial, and topological gapped phases separated by intersecting critical surfaces. The intersections define multicritical lines across which the ground-state energy becomes nonanalytical, concurrent with a closing of the band gap, but with no phase transition taking place.
Calcium carbonate limestone filler is used as a partial replacement for clinker in cements to reduce carbon dioxide emissions and fill the voids in the cement paste. However, concrete durability ...conditions depend on the composition and the water/cement ratio, one of the major origin of concrete´s porosity. The objective of this study was to evaluate physical and chemical effects of calcium carbonate limestone filler in mortar pastes subjected to accelerated carbonation. Composite formulations were elaborated with three proportions of filler substitution (15%, 25% and 35%) and three water/cement ratios (0.42, 0.50 and 0.58). Physical, chemical and mineral characterizations were performed on Portland cement PC V and calcium carbonate limestone. The resulting mortar paste formulations were evaluated with respect to mechanical strength and capillary water absorption both for samples without carbonation and with accelerated exposure conditions. In the latter, carbonation depth penetration was also ascertained. Carbonation effects were determined from X-ray diffraction and thermogravimetric analysis. Results on compression strength and water absorption determined that a 25% filler substitution achieved the best performance with 40.72 MPa and an absorption of up to 7% for the water/cement ratio of 0.42. The carbonation coefficient was primarily affected by the water/cement ratio rather than substitution level. Thermal and mineral analysis indicated that carbonation consumed portlandite and formed calcite. Further calcium carbonate polymorphs were identified after 28 days of accelerated carbonation as a result so far unreported in studies of Portland cement.
Because responses of patients with cancer to immunotherapy can vary in success, innovative predictors of response to treatment are urgently needed to improve treatment outcomes. We aimed to develop ...and independently validate a radiomics-based biomarker of tumour-infiltrating CD8 cells in patients included in phase 1 trials of anti-programmed cell death protein (PD)-1 or anti-programmed cell death ligand 1 (PD-L1) monotherapy. We also aimed to evaluate the association between the biomarker, and tumour immune phenotype and clinical outcomes of these patients.
In this retrospective multicohort study, we used four independent cohorts of patients with advanced solid tumours to develop and validate a radiomic signature predictive of immunotherapy response by combining contrast-enhanced CT images and RNA-seq genomic data from tumour biopsies to assess CD8 cell tumour infiltration. To develop the radiomic signature of CD8 cells, we used the CT images and RNA sequencing data of 135 patients with advanced solid malignant tumours who had been enrolled into the MOSCATO trial between May 1, 2012, and March 31, 2016, in France (training set). The genomic data, which are based on the CD8B gene, were used to estimate the abundance of CD8 cells in the samples and data were then aligned with the images to generate the radiomic signatures. The concordance of the radiomic signature (primary endpoint) was validated in a Cancer Genome Atlas TGCA database dataset including 119 patients who had available baseline preoperative imaging data and corresponding transcriptomic data on June 30, 2017. From 84 input variables used for the machine-learning method (78 radiomic features, five location variables, and one technical variable), a radiomics-based predictor of the CD8 cell expression signature was built by use of machine learning (elastic-net regularised regression method). Two other independent cohorts of patients with advanced solid tumours were used to evaluate this predictor. The immune phenotype internal cohort (n=100), were randomly selected from the Gustave Roussy Cancer Campus database of patient medical records based on previously described, extreme tumour-immune phenotypes: immune-inflamed (with dense CD8 cell infiltration) or immune-desert (with low CD8 cell infiltration), irrespective of treatment delivered; these data were used to analyse the correlation of the immune phenotype with this biomarker. Finally, the immunotherapy-treated dataset (n=137) of patients recruited from Dec 1, 2011, to Jan 31, 2014, at the Gustave Roussy Cancer Campus, who had been treated with anti-PD-1 and anti-PD-L1 monotherapy in phase 1 trials, was used to assess the predictive value of this biomarker in terms of clinical outcome.
We developed a radiomic signature for CD8 cells that included eight variables, which was validated with the gene expression signature of CD8 cells in the TCGA dataset (area under the curve AUC=0·67; 95% CI 0·57–0·77; p=0·0019). In the cohort with assumed immune phenotypes, the signature was also able to discriminate inflamed tumours from immune-desert tumours (0·76; 0·66–0·86; p<0·0001). In patients treated with anti-PD-1 and PD-L1, a high baseline radiomic score (relative to the median) was associated with a higher proportion of patients who achieved an objective response at 3 months (vs those with progressive disease or stable disease; p=0·049) and a higher proportion of patients who had an objective response (vs those with progressive disease or stable disease; p=0·025) or stable disease (vs those with progressive disease; p=0·013) at 6 months. A high baseline radiomic score was also associated with improved overall survival in univariate (median overall survival 24·3 months in the high radiomic score group, 95% CI 18·63–42·1; vs 11·5 months in the low radiomic score group, 7·98–15·6; hazard ratio 0·58, 95% CI 0·39–0·87; p=0·0081) and multivariate analyses (0·52, 0·35–0·79; p=0·0022).
The radiomic signature of CD8 cells was validated in three independent cohorts. This imaging predictor provided a promising way to predict the immune phenotype of tumours and to infer clinical outcomes for patients with cancer who had been treated with anti-PD-1 and PD-L1. Our imaging biomarker could be useful in estimating CD8 cell count and predicting clinical outcomes of patients treated with immunotherapy, when validated by further prospective randomised trials.
Fondation pour la Recherche Médicale, and SIRIC-SOCRATE 2.0, French Society of Radiation Oncology.
We report valley dynamics of spin-singlet (IXS) and spin-triplet (IXT) interlayer excitons in MoS2/WS2 heterostructures subjected to an exchange field. Because of their interlayer character, they ...possess long valley coherence time in addition to long radiative lifetimes, especially for the IXT, which is crucial for valley pseudospin manipulation. Furthermore, the exciton g-factors (g IXS 13.4 and g IXT 17.6) that are more than three times larger than that of intralayer exciton lead to giant valley Zeeman splitting (0.78–1.02 meV/T). Subjected to an exchange field, the competitive interplay among radiative relaxation, thermal excitation between IXS and IXT, and phonon-assisted intervalley scattering significantly enhance photoluminescence intensity (up to 325% for IXS and 1075% for IXT) in the α-valley, while suppressing it in the β-valley. Consequently, the valley polarization of IXS and IXT emissions abruptly converges to unity at low temperatures. At a critical exchange field, valley-selective switching of interlayer exciton states, from IXT to IXS in the β-valley, occurs. Under such a condition, valley polarization retains very high values, above 90% for IXT and 85% for IXS at room temperature. These attractive characteristics make interlayer excitons in MoS2/WS2 heterostructures promising for quantum applications.
Immune checkpoint inhibitors have demonstrated unprecedented clinical activity in a wide range of cancers. Significant therapeutic responses have recently been observed in patients presenting ...mismatch repair-deficient (MMRD) tumours. MMRD cancers exhibit a remarkably high rate of mutations, which can result in the formation of neoantigens, hypothesised to enhance the antitumour immune response. In addition to MMRD tumours, cancers mutated in the exonuclease domain of the catalytic subunit of the DNA polymerase epsilon (POLE) also exhibit an ultramutated genome and are thus likely to benefit from immunotherapy. In this review, we provide an overview of recent data on hypermutated tumours, including MMRD and POLE-mutated cancers, with a focus on their distinctive clinicopathological and molecular characteristics as well as their immune environment. We also discuss the emergence of immune therapy to treat these hypermutated cancers, and we comment on the recent Food and Drug Administration approval of an immune checkpoint inhibitor, the programmed cell death 1 antibody (pembrolizumab, Keytruda), for the treatment of patients with metastatic MMRD cancers regardless of the tumour type. This breakthrough represents a turning point in the management of these hypermutated tumours and paves the way for broader strategies in immunoprecision medicine.
Hyperspectral microscopy is an intriguing technique combining spectroscopy with optical microscopy that can be used to simultaneously obtain spectral and spatial information. The relevance of ...hyperspectral imaging in biomedical applications such as the monitoring of bioimaging agents, the identification of pathogens and cancerous cells, and the cellular uptake of nanoparticles has emerged recently, due to recent advances in optical reconstruction. The location and tracking of particles within the cell structure have been analyzed by 2D hyperspectral imaging of non-fluorescence objects, being examples of 3D localization uncommon. Here, we report the synthesis of Yb3+/Er3+-codoped Gd2O3 nanoparticles, their structural and luminescence characterization, and their biocompatibility assessments in Human melanoma (MNT-1 and A375) cell lines. The internalization of the particles by MNT-1 cells and their 3D localization in a fixed configuration are addressed through 2D optical images acquired in different planes along with the cell culture depth. 2D hyperspectral imaging is used to unequivocally identify the nuclei and the nanoparticles. The results indicate that the particles are distributed in distinct planes deep in the cell volume in the cytoplasmic and perinuclear regions. Furthermore, the emission signature of the nanoparticles enabled the determination of the intracellular temperature.
•The synthesis of Yb3+/Er3+-codoped Gd2O3 nanoparticles, their structural and photoluminescence characterization.•The calculus of the photothermal conversion efficiency of the nanoparticles in air under 980 nm irradiation.•The internalization of the upconverting nanoparticles in Human melanoma (MNT-1 and A375) cell lines, including the viability of the cell lines.•The 3D localization of the Yb3+/Er3+co-doped Gd2O3 nanoparticles through hyperspectral imaging of MNT-1 cells in a fixed configuration. These results indicate that the particles are distributed in distinct plans deep in the cell volume in the cytoplasmic and perinuclear regions.•As an added benefit, the emission signature of the internalized particles enables the determination of the MNT-1 intracellular temperature.
Abstract The scarcity of high-purity limestone subjects the cement industry to consider alternative supplementary cementitious materials for cement production. This research aimed to investigate the ...mechanical properties and the hydration kinetics of cement pastes in the presence of high levels and different fineness of dolomite, especially the formation of thaumasite. A dolomite filler with 20% magnesium oxide, with average diameters of 10 µm, 6 µm and 4 µm was used as a partial replacement for Portland cement at 0%, 15% and 35% in cement pastes cured at 5 ºC and 20 ºC. The results of compressive strength showed similarities in all pastes analyzed, but the fineness of the dolomite showed a significant difference between the strengths obtained. The isothermal calorimetry indicated that the presence of dolomite had a nucleation and dilution effect. The thermogravimetry revealed that dependent of the substitution levels, the pastes with dolomite presented significant differences in the amount of ettringite and carbonate phases. The mineralogical analysis detected the presence of thaumasite only at the temperature of 20 ºC, which this mineral can also form at higher temperatures than those reported in the literature. Finally, we conclude positively about the possibility of using dolomite in cementitious matrices at levels up to 35%, regardless of fineness and curing temperature.
Resumo A escassez de calcário de alta pureza sujeita a indústria cimenteira a considerar materiais cimentícios suplementares alternativos para a produção de cimentos. Esta pesquisa buscou investigar a cinética de hidratação e as propriedades de pastas cimentícias na presença de elevados teores e diferentes finuras de dolomita, em especial à formação de taumasita. Adotou-se um fíler dolomítico com 20% de óxido de magnésio, de diâmetros médios de 10 µm, 6 µm e 4 µm como substituto parcial do cimento Portland nos teores 0%, 15% e 35% em pastas cimentícias curadas a 5 ºC e 20 ºC. Os resultados de resistência à compressão apresentaram semelhanças em todas as pastas analisadas, mas a finura da dolomita mostrou uma diferença significativa entre as médias de resistências obtidas. A calorimetria isotérmica apontou que a presença de dolomita apresentou efeito de nucleação e diluição. A termogravimetria revelou que dependente dos teores de substituição, as pastas com dolomita apresentaram diferenças significativas na quantidade de fases de etringita e carbonatos. A análise mineralógica detectou a presença de taumasita apenas na temperatura de 20 ºC, em que esse mineral também pode se formar em temperaturas mais elevadas do que as temperaturas relatadas na literatura. Por fim, conclui-se positivamente sobre a possibilidade de utilização de dolomita em matrizes cimentícias em teores de até 35%, independente da finura e da temperatura de cura.
Consumidores tem demonstrado mais atençao å qualidade e å funcionalidade dos alimentos consumidos em razao do aumento da incidencia de doenças inflamatórias intestinais, cardiovasculares, hipertensao ...arterial, diabetes mellitus II, obesidade, cánceres, principalmente aquelas relacionadas å intolerancia å lactose e å alergia ås proteínas do leite bovino e da soja. Neste estudo, de forma inédita, foram elaboradas e caracterizadas bebidas probióticas å base de extrato de arroz. As bebidas fermentadas com extrato de arroz (BA) foram desenvolvidas com a inoculaçao de microrganismos Lactobacillus acidophilus, Streptococcus thermophilus e Bifidobacterium animalis ssp. lactis, adoçadas com diferentes tipos de substratos, como sacarose, glicose e mel, e caracterizadas por análises físico-químicas e microbiológicas. Menos tempo de fermentaçao (nove horas) foi alcançado com a adiçao do inóculo SAB 440 (Lactobacillus acidophilus, Streptococcus thermophilus e Bifidobacterium animalis ssp. lactis) e da glicose e mel como substratos nas bebidas de extrato de arroz. Todas as bebidas foram caracterizadas como probióticas porque a contagem de células viáveis foi superior a 106 UFC mL-1. Cabe ressaltar que o valor energético pode se enquadrar como baixo, tendo o conteúdo lipídico sido inferior a 0,03%, o que classifica essas bebidas fermentadas como livres de gordura, de acordo com a legislaçao brasileira vigente. A funcionalidade de bebidas fermentadas elaboradas pode ser atribuida principalmente å sua característica probiótica. As bebidas desenvolvidas sao interessantes para o consumo por pessoas intolerantes å lactose e alérgicas a leite de bovino e soja, pois contem ingredientes nao lácteos.
Este trabalho tem como objetivo apresentar um método de obtenção do nível atingido das competências consideradas de alto valor para uma organização com três unidades de produção em países distintos. ...Para tanto, tem-se o seguinte questionamento: como obter o nível de atendimento das competências de forma a proporcionar ao gestor um panorama realista para a tomada de decisão? Deste questionamento, surge a hipótese de que, com a utilização de Survey estruturado e direcionado às competências de alto valor para a organização, o gestor pode obter informações relevantes para definir suas ações junto aos seus ativos humanos, seja para recompensar as pessoas de forma adequada, desenvolver as capacidades que podem definir o sucesso do negócio e também obter um panorama real e orientado dos principais gaps de competências. Utilizando a pesquisa bibliográfica, pôde-se verificar não apenas a visão de vários autores a respeito da importância do atendimento das competências bem como a forma de obtenção do nível de atendimento delas em um âmbito empresarial. Também com um modelo de Survey, dados sobre o atendimento das competências de alto valor para a empresa pesquisada foram obtidos e analisados.
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