Traveling-wave Thomson scattering for electron-beam spectroscopy

We propose a method to use traveling-wave Thomson scattering for spatiotemporally-resolved electron spectroscopy. This can enable ultrafast time-resolved measurements of the dynamics of relativistic electrons in the presence of extremely intense light fields, either in vacuum or in plasma, such as in laser wakefield accelerators. We demonstrate, with test-particle simulation and analysis, the capability of this technique for measurements of various high field phenomena: radiation reaction of electrons due to scattering, dephasing of a laser wakefield accelerator, and acceleration of electrons in multiple buckets by a laser wakefield. We propose a method to use traveling-wave Thomson scattering for spatiotemporally-resolved electron spectroscopy. This can enable ultrafast time-resolved measurements of the dynamics of relativistic electrons in the presence of extremely intense light fields, either in vacuum or in plasma, such as in laser wakefield accelerators. We demonstrate, with test-particle simulation and analysis, the capability of this technique for measurements of various high field phenomena: radiation reaction of electrons due to scattering, dephasing of a laser wakefield accelerator, and acceleration of electrons in multiple buckets by a laser wakefield

Transport, magnetic, thermodynamic and optical properties in Ti-doped Sr_2RuO_4

We report on electrical resistivity, magnetic susceptibility and magnetization, on heat capacity and optical experiments in single crystals of Sr_2Ru_(1-x)Ti_xO_4. Samples with x=0.1 and 0.2 reveal purely semiconducting resistivity behavior along c and the charge transport is close to localization within the ab-plane. A strong anisotropy in the magnetic susceptibility appears at temperatures below 100 K. Moreover magnetic ordering in c-direction with a moment of order 0.01 mu_B/f.u. occurs at low temperatures. On doping the low-temperature linear term of the heat capacity becomes reduced significantly and probably is dominated by spin fluctuations. Finally, the optical conductivity reveals the anisotropic character of the dc resistance, with the in-plane conductance roughly following a Drude-type behavior and an insulating response along c

Influence of the substrate-induced strain and irradiation disorder on the Peierls transition in TTF-TCNQ microdomains

The influence of the combined effects of substrate-induced strain, finite size and electron irradiation-induced defects have been studied on individual micron-sized domains of the organic charge transfer compound tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ) by temperature-dependent conductivity and current-voltage measurements. The individual domains have been isolated by focused ion beam etching and electrically contacted by focused ion and electron beam induced deposition of metallic contacts. The temperature-dependent conductivity follows a variable range hopping behavior which shows a crossover of the exponent as the Peierls transition is approached. The low temperature behavior is analyzed within the segmented rod model of Fogler, Teber and Shklowskii, as originally developed for a charge-ordered quasi one-dimensional electron crystal. The results are compared with data obtained on as-grown and electron irradiated epitaxial TTF-TCNQ thin films of the two-domain type

Title: Ex vivo coronary stent implantation evaluated with digital image correlation

Abstract: Intracoronary stenting (PCI) has become standard revascularization technique to reopen blocked arteries. Although significant progress in stenting technology and implantation techniques has been made a number of problems remain. Specifically, stent sizing and inflation pressures are still a matter of scientific debates. Despite a large number of biomechanical computational simulations experimental data are rare, likely due to technical difficulties to measure dilatation pressures and coronary dimensions in the same settings. Our study shows that valuable data can be obtained by employing digital image correlation for 3D strain measurement during stent inflation ex-vivo that can provide further insight into the stent-artery wall interactions. Keywords: Artery wall-stent interaction; coronary stent; digital image correlation; experimental implantation; strain. 3 Abstract/Introduction Intracoronary stenting (PCI) has become standard revascularization technique to reopen blocked arteries. Although significant progress in stenting technology and implantation techniques has been made a number of problems remain Despite a large number of biomechanical computational simulations [3, Methods Stent and PCI equipment The balloon-expandable CoCr coronary stent Kaname TM (Terumo Corporation, Tokyo, Japan) with nominal diameter 3.5 mm, and length 15 mm (at pressure 0.9 MPa; and diameter 3.73 mm at 1.6 MPa) was used in this study. The stent was premounted on PCI dilatation catheter RX-2 (Terumo Corporation). Sample The sample of the main branch of the left coronary artery was obtained from autopsy. The male donor was 40 years old and atherosclerotic lesions were presented inside the sample. The experiment was performed 70 hours post mortem. Experiment The sample was mounted into the experimental setup ( Displacement measurement was based on 3D digital image correlation (DIC) conducted with commercial system Dantec Q-450 (Dantec Dynamics, Ulm, Germany). 4 DIC is non-contact optical method based on the stereoscopic principle which is becoming more popular especially within the strain measurement of geometrically nonuniform objects. The algorithm identifies material points on the object surface and the correlation between consecutive images allows material point tracking. Detailed description can be found in the literature The artery was recorded with two digital cameras (NanoSens Mk III, Dantec Dynamics; 1MPx CCD chip; lens Sigma EX, 105 mm, 1:2.8 D Macro) during the balloon expansion (sampling rate 25 Hz). In fully expanded state, the object ROI approx. 18*3 mm*mm was projected onto 600*300 px*px (in each camera). RX2 manometer was recorded with another camera to obtain time course of change of the balloon distending pressure (pressure transducer connected with PC was not available at the time of experiment). The stent was deployed within manual pressurization up to 1.6 MPa which spanned approximately 42 seconds. Results DIC revealed significant overloading of the artery by the expanded stent. The results are depicted in Principal strains' distribution (Green-Lagrange strain is considered within this study) shows artery response within maximally expanded stent. Principal vectors are predominantly aligned with the circumferential and longitudinal direction which is supposed to be the consequence of the cylindrical stent expansion. Circumferential deformation attains 0.5 mm/mm at the peak value which is far beyond physiological situation. The circumferential strain concentration appears non-symmetrically with respect to the length of the sample which is supposed to be the result of irregular reference geometry (an asymmetrical partially occluded lumen of the artery). Six points (P1-6) were chosen to illustrate specific strain values resulting from different loading conditions and atherosclerotic specimen in our experiment. Discussion This is a preliminary report concerning a stent implantation in ex-vivo settings employing a human coronary artery harvested from autopsy. The results suggest that 3D DIC is promising tool suitable for the evaluation of ex-vivo stent implantation potentially useful for validation of computational models and clinical considerations. Presented results suggest that overexpansion of a stent during deployment may overstretch the target site potentially resulting in implantation injury associated with restenosis and/or intimal tears associated with dissections. To obtain exact intraluminal dimensions during stent deployment optical coherence tomography or intravascular ultrasound (IVUS) would be required, currently not available in our laboratory. Nevertheless we plan to combine IVUS with 3D DIC in future experiments

Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a life-threatening stem cell disease characterized by uncontrolled proliferation and accumulation of myeloblasts. Using an advanced RNAi screen-approach in an AML mouse model we have recently identified the epigenetic ‘reader’ BRD4 as a promising target in AML. In the current study, we asked whether inhibition of BRD4 by a small-molecule inhibitor, JQ1, leads to growth-inhibition and apoptosis in primary human AML stem- and progenitor cells. Primary cell samples were obtained from 37 patients with freshly diagnosed AML (n=23) or refractory AML (n=14). BRD4 was found to be expressed at the mRNA and protein level in unfractionated AML cells as well as in highly enriched CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all patients examined. In unfractionated leukemic cells, submicromolar concentrations of JQ1 induced major growth-inhibitory effects (IC50 0.05-0.5 μM) in most samples, including cells derived from relapsed or refractory patients. In addition, JQ1 was found to induce apoptosis in CD34+/CD38− and CD34+/CD38+ stem- and progenitor cells in all donors examined as evidenced by combined surface/Annexin-V staining. Moreover, we were able to show that JQ1 synergizes with ARA-C in inducing growth inhibition in AML cells. Together, the BRD4-targeting drug JQ1 exerts major anti-leukemic effects in a broad range of human AML subtypes, including relapsed and refractory patients and all relevant stem- and progenitor cell compartments, including CD34+/CD38− and CD34+/CD38+ AML cells. These results characterize BRD4-inhibition as a promising new therapeutic approach in AML which should be further investigated in clinical trials

New magnetic phase in metallic V_{2-y}O_3 close to the metal insulator transition

We have observed two spin density wave (SDW) phases in hole doped metallic V_{2-y}O_3, one evolves from the other as a function of doping, pressure or temperature. They differ in their response to an external magnetic field, which can also induce a transition between them. The phase boundary between these two states in the temperature-, doping-, and pressure-dependent phase diagram has been determined by magnetization and magnetotransport measurements. One phase exists at high doping level and has already been described in the literature. The second phase is found in a small parameter range close to the boundary to the antiferromagnetic insulating phase (AFI). The quantum phase transitions between these states as a function of pressure and doping and the respective metamagnetic behavior observed in these phases are discussed in the light of structurally induced changes of the band structure.Comment: REVTeX, 8 pages, 12 EPS figures, submitted to PR

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Antibody-Based and Cell Therapies for Advanced Mastocytosis: Established and Novel Concepts

Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM–AHN). In a vast majority of all patients, neoplastic cells display a KIT mutation, mostly D816V and rarely other KIT variants. Additional mutations in other target genes, such as SRSF2, ASXL1, or RUNX1, may also be identified, especially when an AHN is present. During the past 10 years, improved treatment approaches have led to a better quality of life and survival in patients with advanced SM. However, despite the availability of novel potent inhibitors of KIT D816V, not all patients enter remission and others relapse, often with a multi-mutated and sometimes KIT D816V-negative disease exhibiting multi-drug resistance. For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.Peer reviewe

Clinical impact and proposed application of molecular markers, genetic variants, and cytogenetic analysis in mast cell neoplasms: Status 2022

Mast cell neoplasms are an emerging challenge in the fields of internal medicine, allergy, immunology, dermatology, laboratory medicine, and pathology. In this review, we discuss the current standards for the diagnosis and prognostication of mast cell neoplasms with special reference to clinically relevant germline and somatic gene variants. In patients with cutaneous mastocytosis or with indolent systemic mastocytosis (SM), various KIT-activating mutations act as key molecular drivers of the disease. In adults, KIT p.D816V is by far the most prevalent driver, whereas other KIT mutants are detected in nearly 40% of children. In advanced SM, including aggressive SM, SM with an associated hematological neoplasm, and mast cell leukemia, additional somatic mutations in other genes, such as SRSF2, JAK2, RUNX1, ASXL1, or RAS, may be detected. These drivers are more frequently detected in SM with an associated hematological neoplasm, particularly in male patients. Recently, hereditary alpha-tryptasemia has been identified as a genetic trait more prevalent in SM compared with healthy controls. Moreover, hereditary alpha-tryptasemia is more frequent in patients with SM with Hymenoptera venom allergy and severe mediator-related symptoms than in patients with SM without symptoms. On the basis of this knowledge, we propose a diagnostic algorithm in which genetic markers are applied together with clinical and histopathologic criteria to establish the diagnosis and prognosis in SM