Emergent symmetry in a low-dimensional superconductor on the edge of Mottness.

Upon cooling, condensed-matter systems typically transition into states of lower symmetry. The converse-i.e., the emergence of higher symmetry at lower temperatures-is extremely rare. In this work, we show how an unusually isotropic magnetoresistance in the highly anisotropic, one-dimensional conductor Li0.9Mo6O17 and its temperature dependence can be interpreted as a renormalization group (RG) flow toward a so-called separatrix. This approach is equivalent to an emergent symmetry in the system. The existence of two distinct ground states, Mott insulator and superconductor, can then be traced back to two opposing RG trajectories. By establishing a direct link between quantum field theory and an experimentally measurable quantity, we uncover a path through which emergent symmetry might be identified in other candidate materials.

Micro and nano-scale compartments guide the structural transition of silk protein monomers into silk fibers.

Silk is a unique, remarkably strong biomaterial made of simple protein building blocks. To date, no synthetic method has come close to reproducing the properties of natural silk, due to the complexity and insufficient understanding of the mechanism of the silk fiber formation. Here, we use a combination of bulk analytical techniques and nanoscale analytical methods, including nano-infrared spectroscopy coupled with atomic force microscopy, to probe the structural characteristics directly, transitions, and evolution of the associated mechanical properties of silk protein species corresponding to the supramolecular phase states inside the silkworm's silk gland. We found that the key step in silk-fiber production is the formation of nanoscale compartments that guide the structural transition of proteins from their native fold into crystalline ß-sheets. Remarkably, this process is reversible. Such reversibility enables the remodeling of the final mechanical characteristics of silk materials. These results open a new route for tailoring silk processing for a wide range of new material formats by controlling the structural transitions and self-assembly of the silk protein's supramolecular phases.

Guidelines for the management of asthma in adults and adolescents: Position statement of the South African Thoracic Society - 2021 update.

Asthma prevalence is increasing worldwide, and surveys indicate that most patients in developed and developing countries, including South Africa, do not receive optimal care and are therefore not well controlled. Standard management guidelines adapted to in-country realities are important to support optimal care. The South African Thoracic Society (SATS) first published a guideline for the management of chronic persistent asthma in 1992, which has subsequently been revised several times. The main aim of the present document was to revise and update SATS' statement on the suggested management of chronic asthma, based on the need to promote optimal care and control of asthma, together with the incorporation of new concepts and drug developments. This revised document reinforces optimal care and incorporates the following primary objectives to achieve the recent advances in asthma care: continued emphasis on the use of inhaled corticosteroids (ICS) as the foundation of asthma treatmentto reduce the reliance on short-acting beta-2 agonist (SABA) monotherapy for asthma symptomsto incorporate the evidence and strategy for the use of the combination of an ICS and formoterol for acute symptom relief (instead of a SABA)to incorporate the evidence and strategy for the use of as-needed ICS-long-acting beta agonists (LABA) for patients with infrequent symptoms or 'mild' asthmato incorporate the evidence and strategy for the use of a long-acting muscarinic antagonist (LAMA) in combination with ICS-LABA; andto incorporate the evidence and strategy for the use of and management with a biologic therapy in severe asthma.

Emergence of a real-space symmetry axis in the magnetoresistance of the one-dimensional conductor Li0.9Mo6O17.

We report on an emerging symmetry axis in the magnetoresistance of bulk single crystals of quasi-one-dimensional Li0.9Mo6O17 below T min = 25 K, the temperature at which the electrical resistivity experiences a minimum. Detailed angle-dependent magnetoresistance sweeps reveal that this symmetry axis is induced by the development of a negative magnetoresistance, which is suppressed only for magnetic fields oriented along the poles of the MoO6 octahedra that form the conducting chains. We show that this unusual negative magnetoresistance is consistent with the melting of dark excitons, composed of previously omitted orbitals within the t 2g manifold that order below T min. The unveiled symmetry axis in directional magnetic fields not only provides evidence for the crystallization of these dark excitons but also sheds new light on the long-standing mystery of the metal-insulator transition in Li0.9Mo6O17.

Vascular endothelial growth factor pathway promotes osseointegration and CD31hiEMCNhi endothelium expansion in a mouse tibial implant model: an animal study.

AIMS: It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. MATERIALS AND METHODS: An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31hiEMCNhi endothelium. RNA sequencing analysis was performed using sorted CD31hiEMCNhi endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. RESULTS: Flow cytometry revealed that anti-VEGFR treatment decreased CD31hiEMCNhi vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. CONCLUSION: VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31hiEMCNhi endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108-114.

3d-4f coupling and multiferroicity in frustrated Cairo Pentagonal oxide DyMn2O5.

In solid state science, multifunctional materials and especially multiferroics have attracted a great deal of attention, as they open the possibility for next generation spintronic and data storage devices. Interestingly, while many of them host coexisting 3d and 4f elements, the role of the coupling between these two magnetic entities has remained elusive. By means of single crystal neutron diffraction and inelastic neutron scattering experiments we shed light on this issue in the particular case of the multiferroic oxide DyMn2O5. This compound undergoes a first order magnetic transition from a high temperature incommensurate phase to a low temperature commensurate one. Our investigation reveals that although these two phases have very different magnetic structures, the spin excitations are quite similar indicating a fragile low temperature ground state with respect to the high temperature one. Such a rare scenario is argued to be a manifestation of the competition between the exchange interaction and 4f magnetic anisotropy present in the system. It is concluded that the magnetic structure, hence the ferroelectricity, can be finely tuned depending on the anisotropy of the rare earth.

Evidence for room temperature electric polarization in RMn(2)O(5) multiferroics.

It is established that the multiferroics RMn(2)O(5) crystallize in the centrosymmetric Pbam space group and that the magnetically induced electric polarization appearing at low temperature is accompanied by a symmetry breaking. However, both our present x-ray study-performed on compounds with R=Pr,Nd,Gd,Tb, and Dy-and first-principles calculations unambiguously rule out this picture. Based on structural refinements, geometry optimization, and physical arguments, we demonstrate in this Letter that the actual space group is likely to be Pm. This turns out to be of crucial importance for RMn(2)O(5) multiferroics since Pm is not centrosymmetric. Ferroelectricity is thus already present at room temperature, and its enhancement at low temperature is a spin-enhanced process. This result is also supported by direct observation of optical second harmonic generation. This fundamental result calls into question the actual theoretical approaches that describe the magnetoelectric coupling in this multiferroic family.

Polar and magnetic layered A-site and rock salt B-site-ordered NaLnFeWO6 (Ln = La, Nd) perovskites.

We have expanded the double perovskite family of materials with the unusual combination of layered order in the A sublattice and rock salt order over the B sublattice to compounds NaLaFeWO6 and NaNdFeWO6. The materials have been synthesized and studied by powder X-ray diffraction, neutron diffraction, electron diffraction, magnetic measurements, X-ray absorption spectroscopy, dielectric measurements, and second harmonic generation. At room temperature, the crystal structures of both compounds can be defined in the noncentrosymmetric monoclinic P2(1) space group resulting from the combination of ordering both in the A and B sublattices, the distortion of the cell due to tilting of the octahedra, and the displacement of certain cations. The magnetic studies show that both compounds are ordered antiferromagnetically below T(N) ≈ 25 K for NaLaFeWO6 and at ∼21 K for NaNdFeWO6. The magnetic structure of NaNdFeWO6 has been solved with a propagation vector k = ((1/2) 0 (1/2)) as an antiferromagnetic arrangement of Fe and Nd moments. Although the samples are potential multiferroics, the dielectric measurements do not show a ferroelectric response.

Magnetic and structural studies of the multifunctional material SrFe(0.75)Mo(0.25)O(3-δ).

SrFe0.75Mo0.25O3-δ has been recently discovered as an extremely efficient electrode for intermediate temperature solid oxide fuel cells (IT-SOFCs). We have performed structural and magnetic studies to fully characterize this multifunctional material. We have observed by powder neutron diffraction (PND) and transmission electron microscopy (TEM) that its crystal symmetry is better explained with a tetragonal symmetry (I4/mcm space group) than with the previously reported orthorhombic symmetry (Pnma space group). The temperature dependent magnetic properties indicate an exceptionally high magnetic ordering temperature (TN ∼ 750 K), well above room temperature. The ordered magnetic structure at low temperature was determined by PND to be an antiferromagnetic coupling of the Fe cations. Mössbauer spectroscopy corroborated the PND results. A detailed study, with X-ray absorption spectroscopy (XAS), in agreement with the Mössbauer results, confirmed the formal oxidation states of the cations to be mixed valence Fe(3+/4+) and Mo(6+).

Upper critical magnetic field far above the paramagnetic pair-breaking limit of superconducting one-dimensional Li0:9Mo6O17 single crystals.

The upper critical field H(c2) of purple bronze Li0:9Mo6O17 is found to exhibit a large anisotropy, in quantitative agreement with that expected from the observed electrical resistivity anisotropy. With the field aligned along the most conducting axis, H(c2) increases monotonically with decreasing temperature to a value 5 times larger than the estimated paramagnetic pair-breaking field. Theories for the enhancement of H(c2) invoking spin-orbit scattering or strong-coupling superconductivity are shown to be inadequate in explaining the observed behavior, suggesting that the pairing state in Li0:9Mo6O17 is unconventional and possibly spin triplet.

Guideline for the management of acute asthma in adults: 2013 update.

Acute asthma attacks (asthma exacerbations) are increasing episodes of shortness of breath, cough, wheezing or chest tightness associated with a decrease in airflow that can be quantified and monitored by measurement of lung function (peak expiratory flow (PEF) or forced expiratory volume in the 1st second) and requiring emergency room treatment or admission to hospital for acute asthma and/or systemic glucocorticosteroids for management. The goals of treatment are to relieve hypoxaemia and airflow obstruction as quickly as possible, restore lung function, and provide a suitable plan to avoid relapse. Severe exacerbations are potentially life-threatening and their treatment requires baseline assessment of severity, close monitoring, and frequent reassessment using objective measures of lung function (PEF) and oxygen saturation. Patients at high risk of asthma-related death require particular attention. First-line therapy consists of oxygen supplementation, repeated administration of inhaled short-acting bronchodilators (beta-2-agonists and ipratropium bromide), and early systemic glucocorticosteroids. Intravenous magnesium sulphate and aminophylline are second- and third-line treatment strategies, respectively, for poorly responding patients. Intensive care is indicated for severe asthma that is not responsive to first-line treatment. Antibiotics are only indicated when there are definite features of bacterial infection. Factors that precipitated the acute asthma episode should be identified and preventive measures implemented. Acute asthma is preventable with optimal control of chronic asthma.

Electronic excitations in the correlated metal BaV(0.98)Ti(0.02)S(3) studied using resonant inelastic soft x-ray scattering.

Electronic excitations in the correlated metal BaTi(0.02)V(0.98)S(3) have been studied using resonant inelastic soft x-ray scattering at the V L edge. The intensities of the intra-atomic d-d(*) excitations and the elastic x-ray scattering feature are found to be temperature dependent, with the intensity increasing with decreasing temperature until saturation is reached near 100 K. The behavior of the spectral features is interpreted as evidence of a shift in the 3d electrons from more band-like states at higher temperature to more localized states at low temperature.

Comparison of doctor and patient assessments of asthma control.

INTRODUCTION: The objective of asthma management is to control the condition. However, world-wide surveys reveal that only 5% of asthmatics are well controlled. One reason for this phenomenon is the fact that patients and doctors consistently over-estimate control. This study compared patient and doctor assessment of asthma control. METHODS: A random sample of asthmatics was identified by practitioners in South Africa. Patients completed an Asthma Control Test (ACT) and provided a list of medications currently being taken. The doctor also provided an assessment of control which was summarised into the categories - 'not controlled' and 'controlled' and listed all medications prescribed. RESULTS: The mean ACT score was 12.8 where doctors assessed the patients as being 'not controlled' and 20.7 where doctors assessed the patients as being 'controlled'. Half of the patients classified themselves as being 'not controlled' (ACT score <20, category 1), while doctors classified only 33% of patients as being 'not controlled'. Although only 7% of patients disagreed with the doctor's classification of 'not controlled', 29% disagreed with the doctor's assessment of being 'controlled'. There was a significant difference in ACT score between the sexes (p < 0.0001). Most therapeutic interventions (with the exception of combination products [ICS + LABA]) performed poorly with regard to level of control. CONCLUSION: This study suggests that asthma still appears to be relatively poorly controlled in South Africa, although levels of patient control appear to have improved compared to previous surveys, and confirms that physicians and patients differ in their assessments of asthma control.

Recommendations for locus-specific databases and their curation.

Expert curation and complete collection of mutations in genes that affect human health is essential for proper genetic healthcare and research. Expert curation is given by the curators of gene-specific mutation databases or locus-specific databases (LSDBs). While there are over 700 such databases, they vary in their content, completeness, time available for curation, and the expertise of the curator. Curation and LSDBs have been discussed, written about, and protocols have been provided for over 10 years, but there have been no formal recommendations for the ideal form of these entities. This work initiates a discussion on this topic to assist future efforts in human genetics. Further discussion is welcome.

A structured simple form for ordering genetic tests is needed to ensure coupling of clinical detail (phenotype) with DNA variants (genotype) to ensure utility in publication and databases.

Researchers and clinicians ideally need instant access to all the variation in their gene/locus of interest to efficiently conduct their research and genetic healthcare to the highest standards. Currently much key data resides in the laboratory books or patient records around the world, as there are many impediments to submitting this data. It would be ideal therefore if a semiautomated pathway was available, with a minimum of effort, to make the deidentified data publicly available for others to use. The Human Variome Project (HVP) meeting listed 96 recommendations to work toward this situation. This article is planned to initiate a strategy to enhance the collection of phenotype and genotype data from the clinician/diagnostic laboratory nexus. Thus, the aim is to develop universally applicable forms that people can use when investigating patients for each inherited disease, to assist in satisfying many of the recommendations of the HVP Meeting [Cotton et al., 2007]. We call for comment and collaboration in this article.

Onset of motion and dynamic reordering of a vortex lattice.

Time resolved transport measurements on a driven vortex lattice in an undoped 2H-NbSe2 crystal show that the response to a current pulse is governed by healing of defects as the lattice evolves from a stationary to a moving steady state and that the response time reflects the degree of order in the initial vortex state. We find that stationary field cooled vortex lattices become more ordered with decreasing temperature and identify a temperature below which a qualitative change in the response signals the disappearance of topological defects.

Observation of the vortex lattice spinodal in NbSe2.

Metastable superheated and supercooled vortex states in NbSe2 crystals were probed with fast transport measurements over a wide range of field and temperature. The limit of metastability of the superheated vortex lattice defines a line in the phase diagram that lies below the superconducting transition and is clearly separated from it. This line is identified as the vortex lattice spinodal, and is in good agreement with recent theoretical predictions by Li and Rosenstein [Phys. Rev. B 65, 220504 (2002)]; cond-mat/0305258]. By contrast, no limit of metastability is observed for the supercooled disordered state.

Detailed computational study of p53 and p16: using evolutionary sequence analysis and disease-associated mutations to predict the functional consequences of allelic variants.

Deciding whether a missense allelic variant affects protein function is important in many contexts. We previously demonstrated that a detailed analysis of p53 intragenic conservation correlates with somatic mutation hotspots. Here we refine these evolutionary studies and expand them to the p16/Ink4a gene. We calculated that in order for 'absolute conservation' of a codon across multiple species to achieve P<0.05, the evolutionary substitution database must contain at least 3(M) variants, where M equals the number of codons in the gene. Codons in p53 were divided into high (73% of codons), intermediate (29% of codons), and low (0 codons) likelihood of being mutation hotspots. From a database of 263 somatic missense p16 mutations, we identified only four codons that are mutational hotspots at P<0.05 (8 mutations). However, data on function, structure, and disease association support the conclusion that 11 other codons with > or =5 somatic mutations also likely indicate functionally critical residues, even though P0.05. We calculated p16 evolution using amino acid substitution matrices and nucleotide substitution distances. We looked for evolutionary parameters at each codon that would predict whether missense mutations were disease associated or disrupted function. The current p16 evolutionary substitution database is too small to determine whether observations of 'absolute conservation' are statistically significant. Increasing the number of sequences from three to seven significantly improved the predictive value of evolutionary computations. The sensitivity and specificity for conservation scores in predicting disease association of p16 codons is 70-80%. Despite the small p16 sequence database, our calculations of high conservation correctly predicted loss of cell cycle arrest function in 75% of tested codons, and low conservation correctly predicted wild-type function in 80-90% of codons. These data validate our hypothesis that detailed evolutionary analyses help predict the consequences of missense amino-acid variants.

TP53 mutations in breast cancer associated with BRCA1 or BRCA2 germ-line mutations: distinctive spectrum and structural distribution.

Several groups have studied the molecular pathology of inherited breast cancer. By combining several such studies, we show in this study that somatic TP53 abnormalities are more common in breast cancer associated with BRCA1 or BRCA2 germ-line mutations than in sporadic breast cancers (odds ratio, 2.8; P = 0.0003). Then, we compared the spectrum of TP53 mutations for breast cancers in the IARC TP53 mutation database with the 82 mutations reported in BRCA1/2-associated breast cancers. The spectrum differed significantly both in distribution (P < 1 x 10(-6)) and in base changes (P = 0.025). Mutations at A:T bp were more common in BRCA1/2-associated tumors and strand bias suggesting DNA repair abnormalities was found. Changes were common at TP53 codons that are not mutation hotspots. Structural modeling showed that most of these p53 non-hotspot amino acids characterized in breast tumors isolated from patients with deficient BRCA1/2 function are distributed in a region of the protein on the opposite side of the p53 DNA-binding surface. Our results suggest that BRCA1/2 mutations influence the type and distribution of TP53 mutations seen in breast cancer.

Asthma management and perceptions in rural South Africa.

BACKGROUND: Many First World countries have endeavored to measure the impact of asthma on individuals with asthma and, in addition to this quality of life evaluation, have attempted to define the quality of care for this common chronic illness. OBJECTIVE: The primary objective of this research probe was to assist the National Asthma Program in South Africa with the formulation and delivery of its outreach program to rural asthmatic patients. METHODS: A discussion/questionnaire document was compiled by Partners in Research from established literature. All interviews were conducted in either the clinics, hospitals, or respondents' homes. Both adult asthmatic patients and parents of pediatric asthmatic patients were interviewed. Interviewing took place at seven rural health clinics across South Africa. Each interview included extensive demographic details, questions on asthma definition, symptoms and symptom triggers, family history, age at diagnosis, frequency of symptoms, and treatment. RESULTS: Thirty-five adult asthmatic patients and 27 parents of pediatric asthmatic patients were interviewed. Of the adults, 40% reported wheezing at least once a week (despite diagnosis and treatment) and 19% of children reported similar symptom exacerbations. Fifty-one percent of adults and 56% of children were awakened at least once a week by cough or wheeze. Quality of life measurement reflected that, on average, 37% of responders were frightened during an acute asthma attack, and 68% of parents reported fearing the death of their asthmatic children. Fifty-one percent of adults and 33% of children had been hospitalized at least once for asthma. Although respondents claimed regular training in use of inhaler device, only 43% of adults completed each step correctly. CONCLUSIONS: There is a great deal of fear and ignorance surrounding asthma and, therefore, there is a real need for a greater level of patient education even in the rural areas of South Africa. In rural South Africa, attention should be paid to nurses, because they play a greater role than doctors in management and education of asthma.