Stress deformations and structural quenching in Sm0.5Ca0.5MnO3 thin films allow a huge decrease of the charge order melting magnetic field

Thin films of Sm0.5Ca0.5MnO3 manganites with charge ordering (CO) properties and colossal magnetoresistance were synthesized by pulsed laser deposition technique on (100)-SrTiO3 and (100)-LaAlO3 substrates. We first compare the structural modifications as function of the substrate and film thickness. Secondly, measuring transport properties in magnetic fields up to 24T, we establish the temperature-field phase diagram describing the stability of the CO state and compare it to bulk material. We show that some structural modification induced by the substrate occurs and that the CO melting magnetic field is greatly reduced. Moreover, with the temperature decrease, no modification of the lattice parameters is observed. We then propose an explanation based on the quenching of the unit cell of the film that adopts the in-plane lattice parameters of the substrate and thus, prevents the complete growth of the CO state at low temperature.Comment: to be published in Journal of Applied Physic

Orbital Ordering Structures in (Nd,Pr)0.5Sr0.5MnO3 Manganite Thin Films on Perovskite (011) Substrates

Structural study of orbital-ordered manganite thin films has been conducted using synchrotron radiation, and a ground state electronic phase diagram is made. The lattice parameters of four manganite thin films, Nd0.5Sr0.5MnO3 (NSMO) or Pr0.5Sr0.5MnO3 (PSMO) on (011) surfaces of SrTiO3 (STO) or [(LaAlO3){0.3}(SrAl0.5Ta0.5O3){0.7}] (LSAT), were measured as a function of temperature. The result shows, as expected based on previous knowledge of bulk materials, that the films' resistivity is closely related to their structures. Observed superlattice reflections indicate that NSMO thin films have an antiferro-orbital-ordered phase as their low-temperature phase while PSMO film on LSAT has a ferro-orbital-ordered phase, and that on STO has no orbital-ordered phase. A metallic ground state was observed only in films having a narrow region of A-site ion radius, while larger ions favor ferro-orbital-ordered structure and smaller ions stabilize antiferro-orbital-ordered structure. The key to the orbital-ordering transition in (011) film is found to be the in-plane displacement along [0-1 1] direction.Comment: 19pages, 11 figure

High magnetic field transport measurement of charge-ordered Pr0.5_{0.5}Ca0.5_{0.5}MnO3_3 strained thin films

We have investigated the magnetic-field-induced phase transition of charge-ordered (CO) Pr$_{0.5}$Ca$_{0.5}$MnO$_3$ thin films, deposited onto (100)-oriented LaAlO$_3$ and (100)-oriented SrTiO$_3$ substrates using the pulsed laser deposition technique, by measuring the transport properties with magnetic fields up to 22T. The transition to a metallic state is observed on both substrates by application of a critical magnetic field ($H_C>10T$ at 60K). The value of the field required to destroy the charge-ordered insulating state, lower than the bulk compound, depends on both the substrate and the thickness of the film. The difference of the critical magnetic field between the films and the bulk material is explained by the difference of in-plane parameters at low temperature (below the CO transition). Finally, these results confirm that the robustness of the CO state, depends mainly on the stress induced by the difference in the thermal dilatations between the film and the substrate.Comment: 10 pages, 6 figures. To be published in Phys. Rev.

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay: Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer

BACKGROUND: Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations. METHODS AND FINDINGS: We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per >1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (10(7) copies of gDNA each) or in blood samples from 10 healthy individuals (10(7) copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10(-7), with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput "gene pool" analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals, suggesting that early embryonic EGFR somatic mutation is very rare, inconsistent with hypermutation or strong selection of these deletions in the embryo. 2) The second illustration of MAP utility is in personalized monitoring of therapy and early recurrence in cancer. Tumor-specific p53 mutations identified at diagnosis in the plasma of six patients with stage II and III breast cancer were undetectable after therapy in four women, consistent with clinical remission, and continued to be detected after treatment in two others, reflecting tumor progression. CONCLUSIONS: MAP has an analytical selectivity of one part per billion for detection of MIDIs and an analytical sensitivity of one molecule. MAP provides a general tool for monitoring ultra-rare mutations in tissues and blood. As an example, we show that the personalized cancer signature in six out of six patients with non-metastatic breast cancer can be detected and that levels over time are correlated with the clinical course of disease

Three Ways of Combining Genotyping and Resequencing in Case-Control Association Studies

We describe three statistical results that we have found to be useful in case-control genetic association testing. All three involve combining the discovery of novel genetic variants, usually by sequencing, with genotyping methods that recognize previously discovered variants. We first consider expanding the list of known variants by concentrating variant-discovery in cases. Although the naive inclusion of cases-only sequencing data would create a bias, we show that some sequencing data may be retained, even if controls are not sequenced. Furthermore, for alleles of intermediate frequency, cases-only sequencing with bias-correction entails little if any loss of power, compared to dividing the same sequencing effort among cases and controls. Secondly, we investigate more strongly focused variant discovery to obtain a greater enrichment for disease-related variants. We show how case status, family history, and marker sharing enrich the discovery set by increments that are multiplicative with penetrance, enabling the preferential discovery of high-penetrance variants. A third result applies when sequencing is the primary means of counting alleles in both cases and controls, but a supplementary pooled genotyping sample is used to identify the variants that are very rare. We show that this raises no validity issues, and we evaluate a less expensive and more adaptive approach to judging rarity, based on group-specific variants. We demonstrate the important and unusual caveat that this method requires equal sample sizes for validity. These three results can be used to more efficiently detect the association of rare genetic variants with disease

Production of {\pi}+ and K+ mesons in argon-nucleus interactions at 3.2 AGeV

First physics results of the BM@N experiment at the Nuclotron/NICA complex are presented on {\pi}+ and K+ meson production in interactions of an argon beam with fixed targets of C, Al, Cu, Sn and Pb at 3.2 AGeV. Transverse momentum distributions, rapidity spectra and multiplicities of {\pi}+ and K+ mesons are measured. The results are compared with predictions of theoretical models and with other measurements at lower energies.Comment: 29 pages, 20 figure

Structural characterization of self-organized mono- and multilayers of partly fluorinated polydialkoxyphosphazenes at the air/water interface

We report studies of the collapse of monolayers of mesomorphic poly[bis-(2,2,3,3,4,4,5,5-octafluo-ropentoxy)phosphazene] and poly[bis-(2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptoxy)phosphazene]. The structure of the films has been examined at different stages of the collapse process by synchrotron grazing incidence X-ray diffraction. Surface pressure–surface area isotherms show that these films undergo a stepwise collapse with formation of multilayers. Grazing incidence X-ray diffraction reveals only one diffraction peak for the monolayer as well as for multilayers of the two polymers studied, which corresponds to an in-plane interchain spacing d = 15.2±0.1°Å and 17.6±0.5°Å, respectively. The in-plane correlation length ξxy reaches ca. 500 Å for PFP-C5 (33 macromolecules) and ca. 400 Å for PFP-C7 (23 macromolecules), implying a certain mesoscale order similar to a quasi-long-range one

Phase separation effects in charge-ordered Pr 0.5 Ca 0.5 MnO 3 thin film

Compressed Pr 0.5 Ca 0.5 MnO 3 films (250 nm) deposited on LaAlO 3 have been studied by Electron Spin Resonance technique under high frequency and high magnetic field. We show evidences for the presence of a ferromagnetic phase (FM) embedded in the charge-order phase (CO), in form of thin layers which size depends on the strength and orientation of the magnetic field (parallel or perpendicular to the substrate plane). This FM phase presents an easy plane magnetic anisotropy with an anisotropy constant 100 times bigger than typical bulk values. When the magnetic field is applied perpendicular to the substrate plane, the FM phase is strongly coupled to the CO phase whereas for the parallel orientation it keeps an independent ferromagnetic resonance even when the CO phase becomes antiferromagnetic. Copyright EDP Sciences, Springer-Verlag 200371.27.+a Strongly correlated electron systems; heavy fermions, 76.50.+g Ferromagnetic, antiferromagnetic, and ferrimagnetic resonances; spin-wave resonance, 75.30.Cr Saturation moments and magnetic susceptibilities, 75.25.+z Spin arrangements in magnetically ordered materials (including neutron and spin-polarized electron studies, synchrotron-source X-ray scattering, etc.),