Search for magnetic monopoles produced via the Schwinger mechanism.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production.

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC.

MoEDAL is designed to identify new physics in the form of long-lived highly ionizing particles produced in high-energy LHC collisions. Its arrays of plastic nuclear-track detectors and aluminium trapping volumes provide two independent passive detection techniques. We present here the results of a first search for magnetic monopole production in 13 TeV proton-proton collisions using the trapping technique, extending a previous publication with 8 TeV data during LHC Run 1. A total of 222 kg of MoEDAL trapping detector samples was exposed in the forward region and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges exceeding half the Dirac charge are excluded in all samples and limits are placed for the first time on the production of magnetic monopoles in 13 TeV pp collisions. The search probes mass ranges previously inaccessible to collider experiments for up to five times the Dirac charge.

Search for magnetic monopoles in polar volcanic rocks.

For a broad range of values of magnetic monopole mass and charge, the abundance of monopoles trapped inside Earth would be expected to be enhanced in the mantle beneath the geomagnetic poles. A search for magnetic monopoles was conducted using the signature of an induced persistent current following the passage of igneous rock samples through a SQUID-based magnetometer. A total of 24.6 kg of rocks from various selected sites, among which 23.4 kg are mantle-derived rocks from the Arctic and Antarctic areas, was analyzed. No monopoles were found, and a 90% confidence level upper limit of 9.8 × 10(-5)/g is set on the monopole density in the search samples.

Magnetic properties of silica coated spindle-type hematite particles.

Magnetic properties of particles are generally determined from randomly oriented ensembles and the influence of the particle orientation on the magnetic response is neglected. Here, we report on the magnetic characterization of anisotropic spindle-type hematite particles. The easy axis of magnetization is within the basal plane of hematite, which is oriented perpendicular to the spindle axis. Two standard synthesis routes are compared and the effects of silica coating and particle orientation on the magnetic properties are investigated. Depending on the synthesis route we find fundamentally different magnetic behavior compatible with either single domain particles or superparamagnetic sub-units. Furthermore, we show that silica coating reduces the mean blocking temperature to nearly room temperature. The mechanical stress induced by the silica coating appears to reduce the magnetic coupling between the sub-units.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients.

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Global cooling and enhanced Eocene Asian mid-latitude interior aridity.

Tibetan Plateau uplift has been suggested as the main driving force for mid-latitude Asian inland aridity (AIA) and for deposition of thick aeolian sequences in northern China since the Miocene. However, the relationship between earlier AIA and Tibetan Plateau mountain building is uncertain because of a lack of corresponding thick aeolian sequences with accurate age constraints. We here present results for a continuous aeolian sequence that spans the interval from >51 to 39 Ma from the eastern Xorkol Basin, Altun Shan, northeastern Tibetan Plateau. The basal age of the studied sequence postdates initial uplift of the Tibetan Plateau by several million years. Our results indicate that the local palaeoclimate was teleconnected strongly to the overall global cooling pattern, so that local enhanced aridification recorded by the studied aeolian sequence is dominantly a response to global climatic forcing rather than plateau uplift.

CDK2 catalytic activity and loss of nuclear tethering of retinoblastoma protein in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. During cell cycle progression from the mid- to late G1 phase, mammalian cells traverse the restriction point, a transition from mitogen dependence to mitogen independence, regulated by retinoblastoma protein (Rb). Different cyclin-dependent kinases (CDKs) sequentially phosphorylate and inactivate Rb, which is associated by a change in Rb's nuclear affinity and activation of E2F transcription. Here, we show by in vitro kinase assays that ALL extracts contained CDK2 catalytic activity. When liberation of Rb from cell nuclei was tested by immune precipitation of differential cell extractions and Western blot analysis, little Rb was associated with the nuclear compartment. Together with the immunocytochemical analysis at a single cell level that Rb was phosphorylated at serine 612 and threonine 821, sites known to be phosphorylated by CDK2, the data indicated the presence of CDK2 catalytic activity and loss of Rb's nuclear affinity in ALL cells. We conclude that most ALL cells reside at or beyond the restriction point. This could explain the resistance of ALL cells to differentiation induction.

Reactivity of acute lymphoblastic leukemia and normal bone marrow cells with the monoclonal anti-B-lymphocyte antibody, anti-Y 29/55.

Malignant lymphocyte populations in peripheral blood of patients with B-cell chronic lymphocytic leukemia, leukemic variant of B-cell non-Hodgkin's lymphoma, and hairy cell leukemia can be characterized by the use of a monoclonal murine antibody (anti-Y 29/55) which is directed against a cell membrane component normally confined to the sessile nonrecirculating cells of the B-lymphocyte population in lymphoid tissues. The present report describes the reactivity of the anti-Y 29/55 antibody with bone marrow cells obtained from children with acute lymphoblastic leukemia using an indirect immunofluorescence method in combination with morphological and cytokinetic studies. In 25 patients (acute lymphoblastic leukemia subtype: 14 common; 4 pre-B-cell; 4 null; and 3 T-cell), a maximum of 2% of cells (small lymphocytes) were stained. One patient presented with blasts exhibiting cytoplasmic and surface immunoglobulin M (IgM) (pre-B-B-cell acute lymphoblastic leukemia). About 11% of this patient's blast cells showed a positive reaction with anti-Y 29/55. They could not be differentiated by morphological criteria from the anti-Y 29/55-negative blast cell population. In another patient with pre-B-B-cell acute lymphoblastic leukemia, only 1% of anti-Y 29/55-positive cells was found. In bone marrow of children with relative lymphocytosis, 1.4 to 8.7% of mononuclear cells reacted with anti-Y 29/55. Morphologically, these cells were small lymphocytes and predominantly expressed surface IgM. In two of these children, a further subdivision of bone marrow cells could be achieved by combining anti-Y 29/55 and cytoplasmic IgM reactivity with [3H]thymidine pulse labeling. These studies revealed that the actively proliferating, normal pre-B-cell population was anti-Y 29/55-nonreactive, whereas a nonproliferating population of anti-Y 29/55-reactive, cytoplasmic IgM-positive cells probably represented B-cells with surface immunoglobulin M reacting when cytoplasmic IgM was assessed. We conclude that the reactivity of the monoclonal anti-B-cell antibody (anti-Y 29/55) is restricted to surface immunoglobulin-positive bone marrow cells and that neither leukemic or normal pre-B-cells nor common, null-cell, or T-cell acute lymphoblastic leukemia blasts react.

A lock-in-based method to examine the thermal signatures of magnetic nanoparticles in the liquid, solid and aggregated states.

We propose a new methodology based on lock-in thermography to study and quantify the heating power of magnetic nanoparticles. Superparamagnetic iron oxide nanoparticles exposed to a modulated alternating magnetic field were used as model materials to demonstrate the potency of the system. Both quantitative and qualitative information on their respective heating power was extracted at high thermal resolutions under increasingly complex conditions, including nanoparticles in the liquid, solid and aggregated states. Compared to conventional techniques, this approach offers a fast, sensitive and non-intrusive alternative to investigate multiple and dilute specimens simultaneously, which is essential for optimizing and accelerating screening procedures and comparative studies.

Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiomyopathy associated with intense physical or emotional stress. The precise mechanisms of the disease remain unclear. The aim of this study was to study alterations in endothelial function, vascular compliance and structure and muscle sympathetic activity in the stable phase of the disease. METHODS: In this prospective observational study, patients with TTS and controls matched for age, sex, cardiovascular risk factors and medications were recruited. Flow-mediated vasodilatation (FMD) as a measure of endothelial dysfunction was the primary endpoint. Secondary endpoints included measurements of arterial stiffness, carotid atherosclerosis, quality of life and laboratory parameters. In a subset of patients, muscle sympathetic activity was measured before and after stress tests. RESULTS: The study included 22 TTS patients and 21 matched controls. A significant increase in endothelial dysfunction was seen in TTS compared to controls (FMD 3.4±2.4% vs. 4.8±1.9%, p=0.016). No significant differences in arterial stiffness, intima-media thickness, quality of life and laboratory markers including endothelin-1 were noted. TTS patients showed a reduced carotid total plaque area compared to controls (TPA 17.3±15.1 vs 24.7±12.8mm2, p=0.02). A trend of increased muscle sympathetic activity at rest was observed in TTS patients vs. controls (53.5±28.4 vs. 29.4±16.5 bursts/100 heart beats, p=0.09) with no significant differences in muscle sympathetic activity in response to stress. CONCLUSIONS: Our findings underscore the importance of endothelial dysfunction in patients with TTS which may be involved in the pathophysiology of this syndrome. CLINICALTRIALS. GOV IDENTIFIER: NCT01249599.

Nuclear lamin expression reveals a surprisingly high growth fraction in childhood acute lymphoblastic leukemia cells.

In an attempt to better characterize leukemic bone marrow cells of children with ALL in G0/G1, we studied the variation of the nuclear projection area (NPA) during the cell cycle. Approximately half of the increase of the nuclear volume during the cell cycle occurred before DNA synthesis. Next, we assessed by in situ hybridization (ISH) the expression of nuclear envelope type A/C and type B lamins in leukemic lymphoblast and unstimulated as well as stimulated normal peripheral blood mononuclear cells (PBMC). It was found that 82.0 +/- 16.0% of the ALL cells expressed B-type and 5.8 +/- 3.1% A/C-type lamins. The in vitro 3HdT pulse-labeling index (3HdT LI) of ALL cells varied from 1.3 to 16.8%. Of unstimulated PBMC 2.9 and 1.2% expressed lamin type B and A/C, respectively. The 3HdT LI was 0.8%. In conA-stimulated PBMC, the corresponding values were 95.3 and 74.8% and 31.0%, respectively. In view of the current concepts regarding G1 events and regulation of cell proliferation, we considered B-type lamin expression an early marker for the commitment to proliferation and used it for growth fraction (GF) determinations. By this method, a surprisingly high GF was found in ALL cell populations; there was no correlation between GF and the 3HdT LI, as seen in normal cells.

Proliferation of lymphoid precursor cells in the bone marrow of patients with various disorders of the immune system.

In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling index (3HdT-LI) of TdT-positive bone marrow cells were assessed in patients with different functional activities of the immune system. TdT-positive lymphoid precursor cells could be detected in the bone marrow of all children investigated, including six patients with various forms of immunodeficiency. Neither a transient hyperfunction of the immune system during the immunological rebound after cessation of long-term chemotherapy for acute lymphoblastic leukemia, nor a congenital or acquired hypofunction of the immune system had any detectable influence on the invariably high in vitro 3HdT-LI of TdT-positive bone marrow cells, a phenomenon possibly related to an autonomous and high turnover of this precursor cell compartment in the human bone marrow.

Recovery of megakaryocytopoiesis in vitro in children with acute lymphoblastic leukemia during induction of remission.

In children with acute lymphoblastic leukemia (ALL), megakaryocytopoiesis was investigated in vitro by the semisolid agar culture technique. In untreated ALL the median number of committed megakaryocyte progenitor cells (CFU-Mk) in the bone marrow was 2 (range less than 0.1-8) per 10(5) bone marrow cells instead of 30 (range 14-93) in controls, the impairment being dependent on the degree of leukemic bone marrow infiltration. However, if the number of CFU-Mk was related to residual nonleukemic bone marrow cells only, two-thirds of the children investigated had a frequency of CFU-Mk within the normal range. After 2 weeks of induction therapy the majority of the children had a low number of CFU-Mk in the bone marrow (median 6, range 0.5-40), a fact that could no longer be explained by a dilution of CFU-Mk by leukemic cells. After 4 weeks of chemotherapy (day 29) the frequency of CFU-Mk had risen to 18 (range 3-67) per 10(5) bone marrow cells, a value still significantly (p less than 0.01) below the normal range. In contrast to the changes in the number of CFU-Mk the median cell number per megakaryocyte colony remained constant during induction of remission. After cessation of long-term chemotherapy all children investigated had a normal number of CFU-Mk, suggesting that no permanent chemotherapy-related damage to committed megakaryocyte progenitor cells was induced.

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Effect of ascorbic acid on human natural killer cells.

Ascorbic acid (vitamin C) was found to inhibit human natural killer cell (NK cell) activity in a dose-dependent manner. Neither effector/target cell binding nor interferon (IFN)- or interleukin-2 (IL-2)-induced increases of NK activity were affected by vitamin C. Lymphocytes incubated for 1 h at 4 degrees C with vitamin C showed a normal NK activity, whereas lymphocytes incubated for 1 h at 37 degrees C with vitamin C exhibited low NK activity. Our findings suggest that vitamin C influences NK cells, probably by acting as a radical scavenger which inactivates killing factors of NK cells.

Proliferation of normal and leukemic TdT+ bone marrow cells in man.

Proliferative characteristics of lymphoid cells with detectable amounts of nuclear terminal deoxynucleotidyl transferase (TdT) in normal or regenerating non-leukemic bone marrow of children were assessed by sequential immunological and cytokinetic studies on single cells and compared to those of TdT+ cells in the bone marrow of children with non-T, non-B acute lymphoid leukemia (ALL) at diagnosis or in remission. The median labelling index (LI) of non-leukemic TdT+ cells was 21.3% (range 13.2 to 29.7%). The LI of non-leukemic TdT+Ia+ cells (range 18.2 to 32.6%) was always higher than that of non-leukemic TdT+Ia- cells (range 0 to 5.3%). Leukemic TdT+ bone marrow cells of children with previously untreated non-T, non-B ALL had a LI significantly (p less than 0.001) lower (median 6.1%; range 1.4 to 19.7%) than the LI of non-leukemic TdT+ cells. In patients with non-T, non-B ALL in remission neither the percentage of TdT+ cells nor the LI of TdT+ cells appeared to be useful for detecting early relapse.

Repression of nuclear lamin A and C gene expression in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells.

The lamins A, B and C which are differentially expressed during ontogenesis and differentiation are karyoskeletal proteins forming a polymeric meshwork at the inner nuclear membrane. Using Northern blot analyses we investigated the steady state levels of the three lamin specific RNA transcripts in neoplastic cells derived from 16 untreated patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) and in ALL and NHL established cell lines. Whereas lamin B mRNA was present in all, lamin A and C transcripts were observed in none of the malignant cell samples except one of a common-ALL patient (precursor B-ALL, cytoplasmic mu chain negative). All three lamin mRNAs were detected in normal peripheral blood lymphocytes, however, only after mitogenic stimulation with concanavalin A. Our results provide evidence that expression of lamin A and C is repressed in neoplastic blast cells derived from patients with ALL or NHL and suggest that lamin A and C gene repression is not related to cell proliferation but might be relevant to the differentiated stages of the lymphoid cells in vivo.

Differential phosphorylation of lamin B2 in normal and leukemic cells.

Lamins constitute the nuclear lamina, which underlie the inner membrane of the cell nucleus. Phosphorylation of lamins is a key factor in the regulation of nuclear structure during the cell cycle and of gene transcription. Since an uncontrolled cell cycle and altered gene transcription are major characteristics of neoplasms, we looked for differences in lamin B2 phosphorylation between PBMC, ALL and AML cells. Using different lamin B2-specific antibodies, we detected two different lamin B2 species termed lamin B2 and B2A. Although phosphorylation of lamin B2 in leukemic cells was reminiscent of resting cells, the majority of ALL and AML samples showed significantly higher and more altered lamin B2A phosphorylation compared to PBMC. It remains to be elucidated which mechanism leads to these alterations and whether it could explain the extended G1-phase frequently observed in ALL cells.