Kangaroo Bond Issuance in Australia

The issue of kangaroo bonds (foreign A$-denominated bonds) has become a significant part of the Australian bond market. The Australian experience offers some lessons to other countries interested in developing their domestic bond markets

Incubation with sodium nitrite attenuates fatigue development in intact single mouse fibres at physiological PO2

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordDietary nitrate (NO3−) supplementation, which increases plasma nitrite (NO2−) concentration, has been reported to attenuate skeletal muscle fatigue development. Sarcoplasmic reticulum (SR) calcium (Ca2+) release is enhanced in isolated single skeletal muscle fibres following NO3− supplementation or NO2− incubation at a supra‐physiological PO2 but it is unclear whether NO2− incubation can alter Ca2+ handling and fatigue development at a near‐physiological PO2. We hypothesised that NO2− treatment would improve Ca2+ handling and delay fatigue at a physiological PO2 in intact single mouse skeletal muscle fibres. Each muscle fibre was perfused with Tyrode's solution pre‐equilibrated with either 20% (PO2∼150 Torr) or 2% O2 (PO2 = 15.6 Torr) in the absence and presence of 100 µM NaNO2. At supra‐physiological PO2 (i.e. 20% O2), time to fatigue was lowered by 34% with NaNO2 (control: 257 ± 94 vs. NaNO2: 159 ± 46 s, d = 1.63, P0.05) but [Ca2+]c accumulation between contractions was lower, concomitant with a greater SR Ca2+ pumping rate (P<0.05) compared to the control condition. These results demonstrate that increased exposure to NO2− blunts fatigue development at near‐physiological, but not at supra‐physiological, PO2 through enhancing SR Ca2+ pumping rate in single skeletal muscle fibres. These findings extend our understanding of the mechanisms by which increased NO2− exposure can mitigate skeletal muscle fatigue development.Ministry of Science, Technology and InnovationConselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development)US Department of Health and Human Services (HHS)National Institutes of Health (NIH)National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS

The Intermediate Scale MSSM, the Higgs Mass and F-theory Unification

Even if SUSY is not present at the Electro-Weak scale, string theory suggests its presence at some scale M_{SS} below the string scale M_s to guarantee the absence of tachyons. We explore the possible value of M_{SS} consistent with gauge coupling unification and known sources of SUSY breaking in string theory. Within F-theory SU(5) unification these two requirements fix M_{SS} ~ 5 x 10^{10} GeV at an intermediate scale and a unification scale M_c ~ 3 x 10^{14} GeV. As a direct consequence one also predicts the vanishing of the quartic Higgs SM self-coupling at M_{SS} ~10^{11} GeV. This is tantalizingly consistent with recent LHC hints of a Higgs mass in the region 124-126 GeV. With such a low unification scale M_c ~ 3 x 10^{14} GeV one may worry about too fast proton decay via dimension 6 operators. However in the F-theory GUT context SU(5) is broken to the SM via hypercharge flux. We show that this hypercharge flux deforms the SM fermion wave functions leading to a suppression, avoiding in this way the strong experimental proton decay constraints. In these constructions there is generically an axion with a scale of size f_a ~ M_c/(4\pi)^2 ~ 10^{12} GeV which could solve the strong CP problem and provide for the observed dark matter. The prize to pay for these attractive features is to assume that the hierarchy problem is solved due to anthropic selection in a string landscape.Comment: 48 pages, 8 figures. v3: further minor correction

Resident Memory T Cells (TRM) Are Abundant in Human Lung: Diversity, Function, and Antigen Specificity

Recent studies have shown that tissue resident memory T cells (TRM) are critical to antiviral host defense in peripheral tissues. This new appreciation of TRM that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional TRM that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (TEM) phenotype, though small numbers of central memory T cells (TCM) and T regulatory cells (Treg) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFNγ, as well as TNFα. A significant number of lung TRM CD4+Th cells produced more than one cytokine, identifying them as “multifunctional” Th1 type cells. Finally, lung TRM, but not TRM resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of TRM cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases

Proximal femoral resection arthroplasty for patients with cerebral palsy and dislocated hips: 20 patients followed for 1–6 years

Background and purpose Chronic hip dislocation in non-ambulatory individuals with cerebral palsy (CP) can lead to severe problems, of which pain is often the most severe. We studied the outcome of proximal femoral resection, especially regarding pain, sitting balance, perineal care, and patient satisfaction

Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

Renal involvement is a frequent consequence of plasma cell dyscrasias. The most common entities are light chain amyloidosis, monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Despite a common origin, each condition has its own unique histologic and pathophysiologic characteristic which requires a renal biopsy to distinguish. Recent studies have shown urinary exosomes containing kidney-derived membrane and cytosolic proteins that can be used to probe the proteomics of the entire urinary system from the glomerulus to the bladder. In this study, we analyzed urine exosomes to determine the differences between exosomes from patients with light chain amyloidosis, multiple myeloma, monoclonal gammopathy of undetermined significance, and non-paraproteinemia related kidney disease controls. In patients with light chain amyloidosis, multiple myeloma and monoclonal gammopathy of undetermined significance, immunoreactive proteins corresponding to monomeric light chains were found in exosomes by western blot. In all of the amyloidosis samples with active disease, high molecular weight immunoreactive species corresponding to a decamer were found which were not found in exosomes from the other diseases or in amyloidosis exosomes from patients in remission. Few or no light chains monomeric bands were found in non-paraproteinemia related kidney disease controls. Our results showed that urinary exosomes may have tremendous potential in furthering our understanding of the pathophysiology and diagnosis of plasma cell dyscrasia related kidney diseases

Subcellular localization of Mitf in monocytic cells

Microphthalmia-associated transcription factor (Mitf) is a transcription factor that plays an important role in regulating the development of several cell lineages. The subcellular localization of Mitf is dynamic and is associated with its transcription activity. In this study, we examined factors that affect its subcellular localization in cells derived from the monocytic lineage since Mitf is present abundantly in these cells. We identified a domain encoded by Mitf exon 1B1b to be important for Mitf to commute between the cytoplasm and the nucleus. Deletion of this domain disrupts the shuttling of Mitf to the cytoplasm and results in its retention in the nucleus. M-CSF and RANKL both induce nuclear translocation of Mitf. We showed that Mitf nuclear transport is greatly influenced by ratio of M-CSF/Mitf protein expression. In addition, cell attachment to a solid surface also is needed for the nuclear transport of Mitf

Late pregnancy vitamin D deficiency is associated with doubled odds of birth asphyxia and emergency caesarean section: A prospective cohort study

Objectives: The aim of this prospective cohort study was to investigate the associations between maternal vitamin D status in late pregnancy and emergency caesarean section (EMCS) and birth asphyxia, in a population based sample of women in Sweden. Methods: Pregnant women were recruited at the antenatal care in Sweden and 1832 women were included after exclusion of miscarriages, terminated pregnancies and missing data on vitamin D status. Mode of delivery was retrieved from medical records. EMCS was defined as caesarean section after onset of labour. Birth asphyxia was defined as either 5 min Apgar score < 7 or arterial umbilical cord pH < 7.1. Serum was sampled in the third trimester of pregnancy (T3) and 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography tandem mass spectrometry. Vitamin D deficiency was defined as 25OHD < 30 nmol/L, and associations were studied using logistic regression analysis and expressed as adjusted odds ratios (AOR). Results: In total, 141 (7.7%) women had an EMCS and 58 (3.2%) children were born with birth asphyxia. Vitamin D deficiency was only associated with higher odds of EMCS in women without epidural anaesthesia (AOR = 2.01, p = 0.044). Vitamin D deficiency was also associated with higher odds of birth asphyxia (AOR = 2.22, p = 0.044). Conclusions for Practice: In this Swedish prospective population-based cohort study, vitamin D deficiency in late pregnancy was associated with doubled odds of birth asphyxia and with EMCS in deliveries not aided by epidural anaesthesia. Prevention of vitamin D deficiency among pregnant women may reduce the incidence of EMCS and birth asphyxia. The mechanism behind the findings require further investigation

Regulation of Granulocyte and Macrophage Populations of Murine Bone Marrow Cells by G-CSF and CD137 Protein

BACKGROUND: Granulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis. METHODOLOGY/PRINCIPAL FINDINGS: Both, G-CSF and CD137 protein support proliferation and survival of murine bone marrow cells. G-CSF enhances granulocyte numbers while CD137 protein enhances macrophage numbers. Both growth factors together give rise to more cells than each factor alone. Titration of G-CSF and CD137 protein dose-dependently changes the granulocyte/macrophage ratio in bone marrow cells. Both factors individually induce proliferation of hematopoietic progenitor cells (lin-, c-kit+) and differentiation to granulocytes and macrophages, respectively. The combination of G-CSF and CD137 protein further increases proliferation, and results in a higher number of macrophages than CD137 protein alone, and a lower number of granulocytes than G-CSF alone demonstrating that CD137 protein-induced monocytic differentiation is dominant over G-CSF-induced granulocytic differentiation. CD137 protein induces monocytic differentiation even in early hematopoietic progenitor cells, the common myeloid progenitors and the granulocyte macrophage progenitors. CONCLUSIONS/SIGNIFICANCE: This study confirms earlier data on the regulation of myelopoiesis by CD137 receptor - ligand interaction, and extends them by demonstrating the restriction of this growth promoting influence to the monocytic lineage

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199