Institut Pprime

Materials Science Forum (MSF) is a peer-reviewed journal. The journal scope covers all aspects of theoretical, computational and experimental research in the area of materials science. It includes but is not limited to materials synthesis, analysis of materials properties,the technology of materials processing and materials application. Materials Science Forum is one of the largest periodicals in its field. Materials Science Forum specializes on the publication of thematically complete volumes as well as special topic volumes. Publication of stand-alone papers by individual authors is also considered. All published materials are archived with PORTICO and CLOCKSS. Authors retain the right to publish an extended and significantly updated version in another periodical. Note from the Honorary Editor Emeritus Professor Graeme Murch: I can recommend Materials Science Forum as an excellent location for authors to get their papers published in a fast and stream-lined fashion. Abstracted/Indexed in:SCOPUS www.scopus.com.REAXYS www.reaxys.com. Ei Compendex www.ei.org/. Chimica https://www.elsevier.com/solutions/engineering-village/content#chimica. Inspec (IET, Institution of Engineering Technology) www.theiet.org. Chemical Abstracts Service (CAS) www.cas.org. Google Scholar scholar.google.com. GeoRef www.americangeosciences.org/georef. NASA Astrophysics Data System (ADS) http://www.adsabs.harvard.edu/. INIS Atomindex (International Nuclear Information System) https://inis.iaea.org. Cambridge Scientific Abstracts (CSA) www.csa.com. ProQuest www.proquest.com. Ulrichsweb www.proquest.com/products-services/Ulrichsweb.html. EBSCOhost Research Databases www.ebscohost.com/. Zetoc zetoc.jisc.ac.uk. EVISA http://www.speciation.net/Public/Linklists/EVISA.html. Index Copernicus Journals Master List www.indexcopernicus.com. WorldCat (OCLC) www.worldcat.org.

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers.

<p>Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.</p>

The issue of stress in thin films and functional coatings is a persistent problem in materials science and technology that has congregated many efforts, both from experimental and fundamental points of view, to get a better understanding on how to deal with, how to tailor, and how to manage stress in many areas of applications. With the miniaturization of device components, the quest for increasingly complex film architectures and multiphase systems and the continuous demands for enhanced performance, there is a need toward the reliable assessment of stress on a submicron scale from spatially resolved techniques. Also, the stress evolution during film and coating synthesis using physical vapor deposition (PVD), chemical vapor deposition, plasma enhanced chemical vapor deposition (PECVD), and related processes is the result of many interrelated factors and competing stress sources so that the task to provide a unified picture and a comprehensive model from the vast amount of stress data remains very challenging. This article summarizes the recent advances, challenges, and prospects of both fundamental and applied aspects of stress in thin films and engineering coatings and systems, based on recent achievements presented during the 2016 Stress Workshop entitled “Stress Evolution in Thin Films and Coatings: from Fundamental Understanding to Control.” Evaluation methods, implying wafer curvature, x-ray diffraction, or focused ion beam removal techniques, are reviewed. Selected examples of stress evolution in elemental and alloyed systems, graded layers, and multilayer-stacks as well as amorphous films deposited using a variety of PVD and PECVD techniques are highlighted. Based on mechanisms uncovered by in situ and real-time diagnostics, a kinetic model is outlined that is capable of reproducing the dependence of intrinsic (growth) stress on the grain size, growth rate, and deposited energy. The problems and solutions related to stress in the context of optical coatings, inorganic coatings on plastic substrates, and tribological coatings for aerospace applications are critically examined. This review also suggests strategies to mitigate excessive stress levels from novel coating synthesis perspectives to microstructural design approaches, including the ability to empower crack-based fabrication processes, pathways leading to stress relaxation and compensation, as well as management of the film and coating growth conditions with respect to energetic ion bombardment. Future opportunities and challenges for stress engineering and stress modeling are considered and outlined.

Closed-loop turbulence control is a critical enabler of aerodynamic drag reduction, lift increase, mixing enhancement, and noise reduction. Current and future applications have epic proportion: cars, trucks, trains, airplanes, wind turbines, medical devices, combustion, chemical reactors, just to name a few. Methods to adaptively adjust open-loop parameters are continually improving toward shorter response times. However, control design for in-time response is challenged by strong nonlinearity, high-dimensionality, and time-delays. Recent advances in the field of model identification and system reduction, coupled with advances in control theory (robust, adaptive, and nonlinear) are driving significant progress in adaptive and in-time closed-loop control of fluid turbulence. In this review, we provide an overview of critical theoretical developments, highlighted by compelling experimental success stories. We also point to challenging open problems and propose potentially disruptive technologies of machine learning and compressive sensing.

Turbulent jet noise is a controversial fluid mechanical puzzle that has amused and bewildered researchers for more than half a century. Whereas numerical simulations are now capable of simultaneously predicting turbulence and its radiated sound, the theoretical framework that would guide noise-control efforts is incomplete. Wave packets are intermittent, advecting disturbances that are correlated over distances far exceeding the integral scales of turbulence. Their signatures are readily distinguished in the vortical, turbulent region; the irrotational, evanescent near field; and the propagating far field. We review evidence of the existence, energetics, dynamics, and acoustic efficiency of wave packets. We highlight how extensive data available from simulations and modern measurement techniques can be used to distill acoustically relevant turbulent motions. The evidence supports theories that seek to represent wave packets as instability waves, or more general modal solutions of the governing equations, and confirms the acoustic importance of these structures in the aft-angle radiation of high subsonic and supersonic jets. The resulting unified view of wave packets provides insights that can help guide control strategies.

The present paper is a wide review on AC surface dielectric barrier discharge (DBD) actuators applied to airflow control. Both electrical and mechanical characteristics of surface DBD are presented and discussed. The first half of the present paper gives the last results concerning typical single plate-to-plate surface DBDs supplied by a sine high voltage. The discharge current, the plasma extension and its morphology are firstly analyzed. Then, time-averaged and time-resolved measurements of the produced electrohydrodynamic force and of the resulting electric wind are commented. The second half of the paper concerns a partial list of approaches having demonstrated a significant modification in the discharge behavior and an increasing of its mechanical performances. Typically, single DBDs can produce mean force and electric wind velocity up to 1 mN/W and 7 m/s, respectively. With multi-DBD designs, velocity up to 11 m/s has been measured and force up to 350 mN/m.

Trastuzumab-based therapy has been shown to confer overall survival benefit in HER2-positive patients with advanced gastric cancer in a large multicentric trial (ToGA study). Subgroup analysis identified adenocarcinomas of the stomach and gastroesophageal (GE) junction with overexpression of HER2 according to immunohistochemistry (IHC) as potential responders. Due to recent approval of trastuzumab for HER2 positive metastatic gastric and GE-junction cancer in Europe (EMEA) HER2 diagnostics is now mandatory with IHC being the primary test followed by fluorescence in situ hybridization (FISH) in IHC2+ cases. However, in order to not miss patients potentially responding to targeted therapy determination of a HER2-positive status for gastric cancer required modification of scoring as had been proposed in a pre-ToGA study. To validate this new HER2 status testing procedure in terms of inter-laboratory and inter-observer consensus for IHC scoring a series of 547 gastric cancer tissue samples on a tissue microarray (TMA) was used. In the first step, 30 representative cores were used to identify specific IHC HER2 scoring issues among eight French and German laboratories, while in the second step the full set of 547 cores was used to determine IHC HER2 intensity and area score concordance between six German pathologists. Specific issues relating to discordance were identified and recommendations formulated which proved to be effective to reliably determine HER2 status in a prospective test series of 447 diagnostic gastric cancer specimens.

CD4(+)CD56(+) malignancies are rare hematologic neoplasms, which were recently shown to correspond to the so-called type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study presents the biologic and clinical features of a series of 23 such cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the absence of B, T, and myeloid lineage markers. Clinical presentation typically corresponded to cutaneous nodules associated with lymphadenopathy or spleen enlargement or both. Cytopenia was frequent. Circulating malignant cells were often detected. Massive bone marrow infiltration was seen in 20 of 23 (87%) patients. Most tumor cells exhibited nuclei with a lacy chromatin, a blastic aspect, large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, and cytoplasmic expansions resembling pseudopodia. Other immunophenotypic characteristics included both negative (CD16, CD57, CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA, CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in the absence of chemotherapy. Complete remission was obtained in 18 of 23 (78%) patients after polychemotherapy. Most patients had a relapse in less than 2 years, mainly in the bone marrow, skin, or central nervous system. Considering these clinical and biologic features, the conclusion is made that CD4(+)CD56(+) malignancies constitute a genuine homogeneous entity. Furthermore, some therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the CD4(+)CD56(+) malignant cell are discussed.

The spatio-temporal evolution of a turbulent swirling jet undergoing vortex breakdown has been investigated. Experiments suggest the existence of a self-excited global mode having a single dominant frequency. This oscillatory mode is shown to be absolutely unstable and leads to a rotating counter-winding helical structure that is located at the periphery of the recirculation zone. The resulting time-periodic 3D velocity field is predicted theoretically as being the most unstable mode determined by parabolized stability analysis employing the mean flow data from experiments. The 3D oscillatory flow is constructed from uncorrelated 2D snapshots of particle image velocimetry data, using proper orthogonal decomposition, a phase-averaging technique and an azimuthal symmetry associated with helical structures. Stability-derived modes and empirically derived modes correspond remarkably well, yielding prototypical coherent structures that dominate the investigated flow region. The proposed method of constructing 3D time-periodic velocity fields from uncorrelated 2D data is applicable to a large class of turbulent shear flows.

BACKGROUND: Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. METHODS AND FINDINGS: Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9-155], p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2-) mBCs (19%). HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone metastases and the size of the cohort, which might not have allowed the identification of rare mutations and their effect on survival. CONCLUSIONS: This work reports the results of the analysis of the first large-scale study on mutation profiles of mBC. This study revealed genomic alterations and mutational signatures involved in the resistance to therapies, including actionable mutations.

During the last decade, gene expression profiling of breast cancer has revealed the existence of five molecular subtypes and allowed the establishment of a new classification. The basal subtype, which represents 15-25% of cases, is characterized by an expression profile similar to that of myoepithelial normal mammary cells. Basal tumors are frequently assimilated to triple-negative (TN) breast cancers. They display epidemiological and clinico-pathological features distinct from other subtypes. Their pattern of relapse is characterized by frequent and early relapses and visceral locations. Despite a relative sensitivity to chemotherapy, the prognosis is poor. Recent characterization of their molecular features, such as the dysfunction of the BRCA1 pathway or the frequent expression of EGFR, provides opportunities for optimizing the systemic treatment. Several clinical trials dedicated to basal or TN tumors are testing cytotoxic agents and/or molecularly targeted therapies. This review summarizes the current state of knowledge of this aggressive and hard-to-treat subtype of breast cancer. Keywords: Basal breast cancer, DNA microarrays, prognosis, triple-negative, phenotype, heterogeneous disease, gene expression, taxonomy, basal tumors, genomics, chemotherapy, cytokeratins, P-cadherin, caveolin 1, claudin genes

Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10(-4)) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10(-4)). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10(-4)). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.

The outcome of the adaptive immune response is determined by the integration of both positive and negative signals, respectively, induced upon the triggering of co-signaling receptors. One of them, programmed cell death 1 (PDCD1/PD-1) has largely been shown to be involved in the negative regulation of T-cell activation. However, PD-1 is also expressed on human B cells, and its role(s) in the process of human B-cell activation remains uncertain thus far. In this study, we describe the expression of PD-1 on the major human B-cells subsets isolated from peripheral blood and lymph nodes. We showed that PD-1 was expressed on naive B cells, was differentially expressed on peripheral IgM memory as compared with memory B cells and was lost on germinal center B cells. Expression of PD-1 ligands (PD-Ls) was induced by TLR9 activation. Finally, we showed that PD-1 was recruited to the B-cell receptor upon triggering. We determined that during TLR9 activation, blockade of PD-1/PD-Ls pathways indeed increased B-cell activation, proliferation and the production of inflammatory cytokines. Altogether, our results show, that, as reported in T cells, PD-1/PD-Ls complexes acted as inhibitors of the B-cell activation cascade and highlight the importance of devising future therapies able to modulate lymphocyte activation through the targeting of the PD-1/PD-Ls pathways.

Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3-81) in cohort 1, 37.5% (95% CI 26.4-49.7) in cohort 2 and 29.7% (95% CI 15.9-47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8-64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7-65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960 .).

Ti_nC_n−1T_x2D-sheets are functionalized using a new etching environment allowing the modification of their surface chemistry and production of rationalized TiO₂@MXene nanocomposites.

Elastic moduli of a set of equiatomic alloys (CrFeCoNi, CrCoNi, CrFeNi, FeCoNi, MnCoNi, MnFeNi, and CoNi), which are medium-entropy subsystems of the CrMnFeCoNi high-entropy alloy were determined as a function of temperature over the range 293 K–1000 K. Thermal expansion coefficients were determined for these alloys over the temperature range 100 K–673 K. All alloys were single-phase and had the face-centered cubic (FCC) crystal structure, except CrFeNi which is a two-phase alloy containing a small amount of body-centered cubic (BCC) precipitates in a FCC matrix. The temperature dependences of thermal expansion coefficients and elastic moduli obtained here are useful for quantifying fundamental aspects such as solid solution strengthening, and for structural analysis/design. Furthermore, using the above results, the yield strengths reported in literature for these alloys were normalized by their shear moduli to reveal the influence of shear modulus on solid solution strengthening.

BACKGROUND: Mobile phones and tablets are being increasingly integrated into the daily lives of many people worldwide. Mobile health (mHealth) apps have promising possibilities for optimizing health systems, improving care and health, and reducing health disparities. However, health care apps often seem to be underused after being downloaded. OBJECTIVE: The aim of this paper is to reach a better understanding of people's perceptions, beliefs, and experience of mHealth apps as well as to determine how highly they appreciate these tools. METHODS: A systematic review was carried out on qualitative studies published in English, on patients' perception of mHealth apps between January 2013 and June 2018. Data extracted from these articles were synthesized using a meta-ethnographic approach and an interpretative method. RESULTS: A total of 356 articles were selected for screening, and 43 of them met the inclusion criteria. Most of the articles included populations inhabiting developed countries and were published during the last 2 years, and most of the apps on which they focused were designed to help patients with chronic diseases. In this review, we present the strengths and weaknesses of using mHealth apps from the patients' point of view. The strengths can be categorized into two main aspects: engaging patients in their own health care and increasing patient empowerment. The weaknesses pointed out by the participants focus on four main topics: trustworthiness, appropriateness, personalization, and accessibility of these tools. CONCLUSIONS: Although many of the patients included in the studies reviewed considered mHealth apps as a useful complementary tool, some major problems arise in their optimal use, including the need for more closely tailored designs, the cost of these apps, the validity of the information delivered, and security and privacy issues. Many of these issues could be resolved with more support from health providers. In addition, it would be worth developing standards to ensure that these apps provide patients accurate evidence-based information.

The electrical properties of an asymmetric surface dielectric barrier discharge in atmospheric air have been investigated experimentally. The discharge is used for airflow production close to the dielectric surface, and the time-averaged flow velocity spatial profiles have been measured. Velocities of up to 3.5 m s−1 at heights of 1–2 mm are reached when filamentary discharges with current peaks up to 20 mA are produced along the surface. In terms of powers, mechanical powers (output) of a few milliwatts are obtained for electrical powers (input) up to 10 W. Variation laws or behaviour with several discharge parameters (applied voltage waveform, distance between electrodes, dielectric thickness and permittivity) have been experimentally determined.