17 research outputs found
Neutron spectroscopic study of crystal field excitations in Tb2Ti2O7 and Tb2Sn2O7
We present time-of-flight inelastic neutron scattering measurements at low
temperature on powder samples of the magnetic pyrochlore oxides Tb2Ti2O7 and
Tb2Sn2O7. These two materials possess related, but different ground states,
with Tb2Sn2O7 displaying "soft" spin ice order below Tn~0.87 K, while Tb2Ti2O7
enters a hybrid, glassy spin ice state below Tg~0.2 K. Our neutron
measurements, performed at T=1.5 K and 30 K, probe the crystal field states
associated with the J=6 states of Tb3+ within the appropriate Fd\bar{3}m
pyrochlore environment. These crystal field states determine the size and
anisotropy of the Tb3+ magnetic moment in each material's ground state,
information that is an essential starting point for any description of the
low-temperature phase behavior and spin dynamics in Tb2Ti2O7 and Tb2Sn2O7.
While these two materials have much in common, the cubic stanate lattice is
expanded compared to the cubic titanate lattice. As our measurements show, this
translates into a factor of ~2 increase in the crystal field bandwidth of the
2J+1=13 states in Tb2Ti2O7 compared with Tb2Sn2O7. Our results are consistent
with previous measurements on crystal field states in Tb2Sn2O7, wherein the
ground state doublet corresponds primarily to m_J=|\pm 5> and the first excited
state doublet to mJ=|\pm 4>. In contrast, our results on Tb2Ti2O7 differ
markedly from earlier studies, showing that the ground state doublet
corresponds to a significant mixture of mJ=|\pm 5>, |\mp 4>, and |\pm 2>, while
the first excited state doublet corresponds to a mixture of mJ=|\pm 4>, |\mp
5>, and |\pm 1>. We discuss these results in the context of proposed mechanisms
for the failure of Tb2Ti2O7 to develop conventional long-range order down to 50
mK.Comment: 12 pages, 6 figures. Version is the same as the published one, except
for figure placement on page
Quenched crystal field disorder and magnetic liquid ground states in Tb2Sn2-xTixO7
Solid-solutions of the "soft" quantum spin ice pyrochlore magnets Tb2B2O7
with B=Ti and Sn display a novel magnetic ground state in the presence of
strong B-site disorder, characterized by a low susceptibility and strong spin
fluctuations to temperatures below 0.1 K. These materials have been studied
using ac-susceptibility and muSR techniques to very low temperatures, and
time-of-flight inelastic neutron scattering techniques to 1.5 K. Remarkably,
neutron spectroscopy of the Tb3+ crystal field levels appropriate to at high
B-site mixing (0.5 < x < 1.5 in Tb2Sn2-xTixO7) reveal that the doublet ground
and first excited states present as continua in energy, while transitions to
singlet excited states at higher energies simply interpolate between those of
the end members of the solid solution. The resulting ground state suggests an
extreme version of a random-anisotropy magnet, with many local moments and
anisotropies, depending on the precise local configuration of the six B sites
neighboring each magnetic Tb3+ ion.Comment: 6 pages, 6 figure
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Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production
Atrial natriuretic peptide (ANP) has a central role in regulating blood pressure in humans. Recently, microRNA 425 (miR-425) was found to regulate ANP production by binding to the mRNA of NPPA, the gene encoding ANP. mRNAs typically contain multiple predicted microRNA (miRNA)-binding sites, and binding of different miRNAs may independently or coordinately regulate the expression of any given mRNA. We used a multifaceted screening strategy that integrates bioinformatics, next-generation sequencing data, human genetic association data, and cellular models to identify additional functional NPPA-targeting miRNAs. Two novel miRNAs, miR-155 and miR-105, were found to modulate ANP production in human cardiomyocytes and target genetic variants whose minor alleles are associated with higher human plasma ANP levels. Both miR-15 and miR-105 repressed NPPA mRNA in an allele-specific manner, with the minor allele of each respective variant conferrin resistance to the miRNA either by disruption of miRNA base pairing or by creation of wobble base pairing. Moreover, miR-15 enhanced the repressive effects of miR-425 on ANP production in human cardiomyocytes. Our study combines computational genomic, and cellular tools to identify novel miRNA regulators of ANP production that could be targeted to raise ANP levels which may have applications for the treatment of hypertension or heart failure
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
Supplementary Material for: Increased Bone Morphogenetic Protein Signaling in the Cutaneous Vasculature of Patients with Calciphylaxis
<b><i>Background:</i></b> The objective of this study was to investigate the role of bone morphogenetic protein (BMP) signal transduction in the pathogenesis of calciphylaxis. <b><i>Methods:</i></b> Skin biopsy specimens were obtained from 18 patients with, and 12 patients without, calciphylaxis. Tissue sections were stained with antibodies directed against BMP effector proteins phosphorylated-SMAD (p-SMAD) 1/5/9, inhibitor of DNA 1 (Id1), inhibitor of DNA 3 (Id3), and Runx2. The intensity of staining was scored semi-quantitatively as strong versus weak or absent. <b><i>Results:</i></b> Of the 18 patients with calciphylaxis (mean age: 59 ± 8 years), 9 were women and 15 had end-stage renal disease. Of the 12 control patients (mean age: 57 ± 10 years), 8 were women and 8 had end-stage renal disease. Strong staining for p-SMAD 1/5/9 was detected in blood vessels from all calciphylaxis patients. In 1 patient with calciphylaxis, strong staining for p-SMAD 1/5/9 was detected in a blood vessel that did not have evidence of calcification. Id1 and Id3 immunoreactivity was detected in blood vessels from all 12 patients with calciphylaxis that were tested. Runx2 staining was detected in all 6 patients with calciphylaxis who were tested. p-SMAD 1/5/9 immunoreactivity was weak or absent in blood vessels of 10 of the 12 control samples. <b><i>Conclusions:</i></b> The BMP signal transduction pathway is activated in the cutaneous vasculature of calciphylaxis patients. The ability to detect p-SMAD 1/5/9, Id1, and Id3 in cutaneous vasculature may assist in the diagnosis of calciphylaxis. As BMP signaling inhibitors become available, this pathway may serve as a future therapeutic target for calciphylaxis
Expanding the Genetic and Phenotypic Spectrum of Popliteal Pterygium Disorders
The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development. (c) 2015 Wiley Periodicals, Inc