Context. Over the past 40 years, helioseismology has been enormously successful in the study of the solar interior. A shortcoming has been the lack of a convincing detection of the solar g modes, ...which are oscillations driven by gravity and are hidden in the deepest part of the solar body – its hydrogen-burning core. The detection of g modes is expected to dramatically improve our ability to model this core, the rotational characteristics of which have, until now, remained unknown. Aims. We present the identification of very low frequency g modes in the asymptotic regime and two important parameters that have long been waited for: the core rotation rate, and the asymptotic equidistant period spacing of these g modes. Methods. The GOLF instrument on board the SOHO space observatory has provided two decades of full-disk helioseismic data. The search for g modes in GOLF measurements has been extremely difficult because of solar and instrumental noise. In the present study, the p modes of the GOLF signal are analyzed differently: we search for possible collective frequency modulations that are produced by periodic changes in the deep solar structure. Such modulations provide access to only very low frequency g modes, thus allowing statistical methods to take advantage of their asymptotic properties. Results. For oscillatory periods in the range between 9 and nearly 48 h, almost 100 g modes of spherical harmonic degree 1 and more than 100 g modes of degree 2 are predicted. They are not observed individually, but when combined, they unambiguously provide their asymptotic period equidistance and rotational splittings, in excellent agreement with the requirements of the asymptotic approximations. When the period equidistance has been measured, all of the individual frequencies of each mode can be determined. Previously, p-mode helioseismology allowed the g-mode period equidistance parameter P0 to be bracketed inside a narrow range, between approximately 34 and 35 min. Here, P0 is measured to be 34 min 01 s, with a 1 s uncertainty. The previously unknown g-mode splittings have now been measured from a non-synodic reference with very high accuracy, and they imply a mean weighted rotation of 1277 ± 10 nHz (9-day period) of their kernels, resulting in a rapid rotation frequency of 1644 ± 23 nHz (period of one week) of the solar core itself, which is a factor 3.8 ± 0.1 faster than the rotation of the radiative envelope. Conclusions. The g modes are known to be the keys to a better understanding of the structure and dynamics of the solar core. Their detection with these precise parameters will certainly stimulate a new era of research in this field.
We have examined the global structure of the solar magnetic field using data from the Fe i spectral line at 5250.2 Angstrom obtained at the 150 foot tower telescope at the Mt. Wilson Observatory. For ...each point on the solar surface, we find the value of the magnetic field in the meridional plane, Bm, by averaging over all available observations using a cosine weighting method. We have revised our cosine weighting method by now taking into account more fully the highest latitude geometry. We use the annual variation in the latitude of the disk center, b sub(0), to deduce the tilt angle of the field relative to the local vertical so that we can find the radial component of the field, Br, from Bm. We find this tilt angle to be small except for a near-polar zone where a tilt-angle model can reduce the annual variation. The reduced annual variation in the deduced Br allows us to study d Br/dt and associated deviations in Br from a smoothed Br with a smoothing width of 2.5 yr. These functions make evident the presence of small amplitude (3-5 G) but spatially coherent ripples with a semi-regular periodicity of one to three years. At any given time, the half-wavelength (peak to trough) is between 15degrees and 30degrees of latitude. These patterns are ubiquitous and in many cases drift from near the equator to the poles over a time period of roughly two years. The drift rate pattern is not compatible with simple advection.
Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably ...silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.
Abstract
Extrapolations of line-of-sight photospheric field measurements predict radial interplanetary magnetic field (IMF) strengths that are factors of ∼2–4 too low. To address this
open flux ...problem
, we reanalyze the magnetograph measurements from different observatories, with particular focus on those made in the saturation-prone Fe
i
525.0 nm line by the Mount Wilson Observatory (MWO) and the Wilcox Solar Observatory (WSO). The total dipole strengths, which determine the total open flux, generally show large variations among observatories, even when their total photospheric fluxes are in agreement. However, the MWO and WSO dipole strengths, as well as their total fluxes, agree remarkably well with each other, suggesting that the two data sets require the same scaling factor. As shown earlier by Ulrich et al., the saturation correction
δ
−1
derived by comparing MWO measurements in the 525.0 nm line with those in the nonsaturating Fe
i
523.3 nm line depends sensitively on where along the irregularly shaped 523.3 nm line wings the exit slits are placed. If the slits are positioned so that the 523.3 and 525.0 nm signals originate from the same height,
δ
−1
∼ 4.5 at the disk center, falling to ∼2 near the limb. When this correction is applied to either the MWO or WSO maps, the derived open fluxes are consistent with the observed IMF magnitude. Other investigators obtained scaling factors only one-half as large because they sampled the 523.3 nm line farther out in the wings, where the shift between the right- and left-circularly polarized components is substantially smaller.
Children and adolescents with Crohn’s disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and ...emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn’s and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
Objectives
To evaluate matrix‐assisted laser desorption ionisation time of flight mass spectrometry (MALDI‐TOF MS) combined with the Sepsityper kit (Bruker Daltoniks GmbH, Bremen) for the direct ...detection of bacterial species from inoculated blood cultures from dogs and cats.
Materials and Methods
Canine and feline blood samples were inoculated with typical sepsis‐causing bacteria such as Staphylococcus intermedius, Staphylococcus aureus, Streptococcus canis, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa at two distinct concentrations (each in triplicate), resulting in 72 blood culture bottles incubated at 37°C. Samples were comparatively analysed with MALDI‐TOF MS after preparation with the Sepsityper kit and also by standard bacteriology (culturing and biochemical characterisation).
Results
Bacterial species identified from agar plates and by MALDI‐TOF MS from blood culture bottles were identical for all samples. The MALDI Biotyper software (Bruker Daltoniks) correctly identified all bacterial strains from inoculated canine and feline blood with analysis indicating very good precision.
Clinical Significance
MALDI‐TOF MS analysis combined with the Sepsityper kit is a reliable tool for a quick detection of veterinary‐relevant bacterial species directly from blood culture bottles. This approach could reduce the time for identification of critical species to only 24 hours.
Background & Aims A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on a ...second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). Methods We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. Results Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance ( preplication <0.05) in the replication. The most robust novel association was detected at chromosome 1p36 (rs3748816; pcombined = 2.1 × 10−8 ) where the MMEL1 and TNFRSF14 genes represent potential disease genes. Eight additional novel loci showed suggestive evidence of association ( prepl <0.05). FUT2 at chromosome 19q13 (rs602662; pcomb = 1.9 × 10−6 , rs281377; pcomb = 2.1 × 10−6 and rs601338; pcomb = 2.7 × 10−6 ) is notable due to its implication in altered susceptibility to infectious agents. We found that FUT2 secretor status and genotype defined by rs601338 significantly influence biliary microbial community composition in PSC patients. Conclusions We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC.
This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence ...variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
ABSTRACT
Hantavirus-induced diseases are emerging zoonoses with endemic appearances and frequent outbreaks in different parts of the world. In humans, hantaviral pathology is characterized by the ...disruption of the endothelial cell barrier followed by increased capillary permeability, thrombocytopenia due to platelet activation/depletion and an overactive immune response. Genetic vulnerability due to certain human leukocyte antigen haplotypes is associated with disease severity. Typically, two different hantavirus-caused clinical syndromes have been reported: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The primarily affected vascular beds differ in these two entities: renal medullary capillaries in HFRS caused by Old World hantaviruses and pulmonary capillaries in HCPS caused by New World hantaviruses. Disease severity in HFRS ranges from mild, e.g. Puumala virus-associated nephropathia epidemica, to moderate, e.g. Hantaan or Dobrava virus infections. HCPS leads to a severe acute respiratory distress syndrome with high mortality rates. Due to novel insights into organ tropism, hantavirus-associated pathophysiology and overlapping clinical features, HFRS and HCPS are believed to be interconnected syndromes frequently involving the kidneys. As there are no specific antiviral treatments or vaccines approved in Europe or the USA, only preventive measures and public awareness may minimize the risk of hantavirus infection. Treatment remains primarily supportive and, depending on disease severity, more invasive measures (e.g., renal replacement therapy, mechanical ventilation and extracorporeal membrane oxygenation) are needed.
The solvent formation of phenobarbital, an important drug compound with an unusually complex polymorphic behavior, was studied in detail. Monosolvates with acetonitrile, nitromethane, ...dichloromethane, and 1,4-dioxane were produced and characterized by single-crystal and powder X-ray diffraction, thermoanalytical methods, FT-IR, Raman, and solid-state NMR spectroscopy. Thermal desolvation of these compounds yields mainly mixtures of polymorphs III, II, and I. At a low relative humidity (25 °C) the solvates transform to polymorph III, and at higher relative humidity the monohydrate and the metastable polymorphs IV and VI can be present as additional desolvation products. These results highlight the potential complexity of desolvation reactions and illustrate that a tight control of ambient conditions is a prerequisite for the production of phase-pure raw materials of drug compounds. Transformation in aqueous media results in the monohydrate. Below room temperature, the 1,4-dioxane monosolvate undergoes a reversible single-crystal-to-single-crystal phase transition due to the ordering/disordering of 50% of its solvent molecules. Dipolar-dephasing NMR experiments show that the solvent molecules are relatively mobile. Deuterium NMR spectra reinforce that conclusion for the dioxane solvent molecules. The crystal structure of an elusive 1,4-dioxane hemisolvate was also determined. This study clearly indicates the existence of “transient solvates” of phenobarbital. The formation of unstable phases of this kind must be considered in order to better understand how different solvents affect the crystallization of specific polymorphs.
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