Nano-structured silicon anodes are attractive alternatives to graphitic carbons in rechargeable Li-ion batteries, owing to their extremely high capacities. Despite their advantages, numerous issues ...remain to be addressed, the most basic being to understand the complex kinetics and thermodynamics that control the reactions and structural rearrangements. Elucidating this necessitates real-time in situ metrologies, which are highly challenging, if the whole electrode structure is studied at an atomistic level for multiple cycles under realistic cycling conditions. Here we report that Si nanowires grown on a conducting carbon-fibre support provide a robust model battery system that can be studied by (7)Li in situ NMR spectroscopy. The method allows the (de)alloying reactions of the amorphous silicides to be followed in the 2nd cycle and beyond. In combination with density-functional theory calculations, the results provide insight into the amorphous and amorphous-to-crystalline lithium-silicide transformations, particularly those at low voltages, which are highly relevant to practical cycling strategies.
Atomic nuclei are composite systems, and they may be dynamically excited during nuclear reactions. Such excitations are not only relevant to inelastic scattering but they also affect other reaction ...processes such as elastic scattering and fusion. The coupled-channels approach is a framework which can describe these reaction processes in a unified manner. It expands the total wave function of the system in terms of the ground and excited states of the colliding nuclei, and solves the coupled Schrödinger equations to obtain the S-matrix, from which several cross sections can be constructed. This approach has been a standard tool to analyze experimental data for nuclear reactions. In this paper, we review the present status and the recent developments of the coupled-channels approach. This includes the microscopic coupled-channels method and its application to cluster physics, the continuum discretized coupled-channels (CDCC) method for breakup reactions, the semi-microscopic approach to heavy-ion subbarrier fusion reactions, the channel coupling effects on nuclear astrophysics and syntheses of superheavy elements, and inclusive breakup and incomplete fusion reactions of weakly-bound nuclei.
The terms mélange and broken formation have been used in different ways in the literature. The lack of agreement on their definition often leads to confusion and misinterpretations. An evaluation of ...the various uses of these terms allows us to consider several types of chaotic rock bodies originated by tectonic, sedimentary and diapiric processes in different tectonic settings. Our review of stratal disruption and mixing processes shows that there exists a continuum of deformation structures and processes in the generation of mélanges and broken formations. This continuum is directly controlled by the increase of the degree of consolidation with burial. In tectonically active environments, at the shallow structural levels, the occurrence of poorly consolidated sediments favors gravitational deformation. At deeper structural levels, the deformation related to tectonic forces becomes gradually more significant with depth. Sedimentary (and diapiric) mélanges and broken formations represent the products of punctuated stratal disruption mechanisms recording the instantaneous physical conditions in the geological environment at the time of their formation. The different kinematics, the composition and lithification degree of sediments, the geometry and morphology of the basins, and the mode of failure propagation control the transition between different types of mass-transported chaotic bodies, the style of stratal disruption, and the amount of rock mixing. Tectonically broken formations and mélanges record a continuum of deformation that occurs through time and different degrees of lithification during a progressive increase of the degree of consolidation and of the diagenetic and metamorphic mineral transformation. Systematic documentation of the mechanisms and processes of the formation of different broken formations and mélanges and their interplay in time and space are highly important to increase the understanding of the evolutionary history of accretionary wedges and orogenic belts.
►Re-evaluation of the definitions of the terms mélange and broken formation. ►Tectonic, sedimentary and diapiric mélanges in different tectonic settings. ►Mechanisms and processes of stratal disruption and mixing.
Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by ...cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1(+) HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1(-) HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma.
Probe electrospray ionization mass spectrometry (PESI‐MS) is an ambient ionization‐based mass spectrometry method that surpasses the original electrospray ionization technique in features such as the ...rapidity of analysis, simplicity of the equipment and procedure, and lower cost. This study found that the PESI‐MS system with machine learning has the potential to establish a lipid‐based diagnosis of breast cancer with higher accuracy, using a simpler approach.
Rapid mass spectrometry for breast cancer
Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the ...techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique.
Definite progress has been made in the exploration of myelodysplastic syndromes (MDS) by flow cytometry (FCM) since the publication of the World Health Organization 2008 classification of myeloid ...neoplasms. An international working party initiated within the European LeukemiaNet and extended to include members from Australia, Canada, Japan, Taiwan and the United States has, through several workshops, developed and subsequently published consensus recommendations. The latter deal with preanalytical precautions, and propose small and large panels, which allow evaluating immunophenotypic anomalies and calculating myelodysplasia scores. The current paper provides guidelines that strongly recommend the integration of FCM data with other diagnostic tools in the diagnostic work-up of MDS.
The current World Health Organization classification of myelodysplastic syndromes is based morphological evaluation of bone marrow dysplasia. In clinical practice, the reproducibility of the ...recognition of dysplasia is usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities.
We aimed to develop and validate a flow cytometric score for the diagnosis of myelodysplastic syndrome. Four reproducible parameters were analyzed: CD34(+) myeloblast-related and B-progenitor-related cluster size (defined by CD45 expression and side scatter characteristics CD34(+) marrow cells), myeloblast CD45 expression and granulocyte side scatter value. The study comprised a "learning cohort" (n=538) to define the score and a "validation cohort" (n=259) to confirm its diagnostic value.
With respect to non-clonal cytopenias, patients with myelodysplastic syndrome had increased myeloblast-related cluster size, decreased B-progenitor-related cluster size, aberrant CD45 expression and reduced granulocyte side scatter (P<0.001). To define the flow cytometric score, these four parameters were combined in a regression model and the weight for each variable was estimated based on coefficients from that model. In the learning cohort a correct diagnosis of myelodysplastic syndrome was formulated in 198/281 cases (sensitivity 70%), while 18 false-positive results were noted among 257 controls (specificity 93%). Sixty-five percent of patients without specific markers of dysplasia (ring sideroblasts and clonal cytogenetic abnormalities) were correctly classified. A high value of the flow cytometric score was associated with multilineage dysplasia (P=0.001), transfusion dependency (P=0.02), and poor-risk cytogenetics (P=0.04). The sensitivity and specificity in the validation cohort (69% and 92%, respectively) were comparable to those in the learning cohort. The likelihood ratio of the flow cytometric score was 10.
A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate.
1 Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
2 Faculty of Medicine & CHU, Nancy Université, France
3 Department of Hematology and Oncology, Fondazione IRCCS ...Policlinico San Matteo, Pavia, and University of Pavia, Italy
4 Laboratoire dHématologie, CHU Dupuytren, Limoges, France
5 Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6 Department of Hematology Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany
7 Department of Hematology and Oncology, Georg-August-University, Göttingen, Germany
8 Sanquin Research at CLB, Amsterdam, The Netherlands
9 Kings College Hospital, London, United Kingdom
10 Department of Hematology, St Radboud University Medical Center, Nijmegen, The Netherlands
11 MLL Munich Leukemia Laboratory, Munich, Germany
12 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
13 Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
14 Servicio Central de Citometría, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer (CSIC/USAL) and Department of Medicine, Universidad de Salamanca, Spain
15 Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
16 HMDS, St. Jamess University Hospital, Leeds, United Kingdom
17 Department of Hematology, Fundación Jiménez Díaz, Madrid, Spain
18 Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
19 Department of Hematology, Weatherall Institute of Molecular Medicine University of Oxford and John Radcliffe Hospital, Oxford, United Kingdom
20 Hematologics, Inc., Seattle, WA, USA
Correspondence: Arjan A. van de Loosdrecht, MD, PhD, Department of Hematology, VU-Institute of Cancer and Immunology, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. E-mail: a.vandeloosdrecht{at}vumc.nl
The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing cells in dysplastic bone marrow point to a useful role for multiparameter flow cytometry (FCM) in the diagnosis and prognostication of myelodysplastic syndromes. In March 2008, representatives from 18 European institutes participated in a European LeukemiaNet (ELN) workshop held in Amsterdam as a first step towards standardization of FCM in myelodysplastic syndromes. Consensus was reached regarding standard methods for cell sampling, handling and processing. The group also defined minimal combinations of antibodies to analyze aberrant immunophenotypes and thus dysplasia. Examples are altered numbers of CD34 + precursors, aberrant expression of markers on myeloblasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers. When applied in practice, aberrant FCM patterns correlate well with morphology, the subclassification of myelodysplastic syndromes, and prognostic scoring systems. However, the group also concluded that despite strong evidence for an impact of FCM in myelodysplastic syndromes, further (prospective) validation of markers and immunophenotypic patterns are required against control patient groups as well as further standardization in multi-center studies. Standardization of FCM in myelodysplastic syndromes may thus contribute to improved diagnosis and prognostication of myelodysplastic syndromes in the future.
Key words: myelodysplastic syndromes, flow cytometry, standardization, ELN, consensus.
Related Article
Flow cytometry immunophenotyping for diagnosis of myelodysplastic syndrome
Mario Cazzola
Haematologica 2009 94: 1041-1043.
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