Quantitative and O2 Enhanced MRI of the Pathologic Lung: Findings in Emphysema, Fibrosis, and Cystic Fibrosis

Purpose: beyond the pure morphological visual representation, MR imaging offers the possibility to quantify parameters in the healthy, as well as, in pathologic lung parenchyma. Gas exchange is the primary function of the lung and the transport of oxygen plays a key role in pulmonary physiology and pathophysiology. The purpose of this review is to present a short overview of the relaxation mechanisms of the lung and the current technical concepts of T1 mapping and methods of oxygen enhanced MR imaging. Material and Methods: molecular oxygen has weak paramagnetic properties so that an increase in oxygen concentration results in shortening of the T1 relaxation time and thus to an increase of the signal intensity in T1 weighted images. A possible way to gain deeper insights into the relaxation mechanisms of the lung is the calculation of parameter Maps. T1 Maps based on a snapshot FLASH sequence obtained during the inhalation of various oxygen concentrations provide data for the creation of the so-called oxygen transfer function (OTF), assigning a measurement for local oxygen transfer. T1 weighted single shot TSE sequences also permit expression of the signal changing effects associated with the inhalation of pure oxygen. Results: the average of the mean T1 values over the entire lung in inspiration amounts to 1199 +/− 117 milliseconds, the average of the mean T1 values in expiration was 1333 +/− 167 milliseconds. T1 Maps of patients with emphysema and lung fibrosis show fundamentally different behavior patterns. Oxygen enhanced MRT is able to demonstrate reduced diffusion capacity and diminished oxygen transport in patients with emphysema and cystic fibrosis. Discussion: results published in literature indicate that T1 mapping and oxygen enhanced MR imaging are promising new methods in functional imaging of the lung and when evaluated in conjunction with the pure morphological images can provide additional valuable information

Finite-temperature mutual information in a simple phase transition

We study the finite-temperature behavior of the Lipkin-Meshkov-Glick model, with a focus on correlation properties as measured by the mutual information. The latter, which quantifies the amount of both classical and quantum correlations, is computed exactly in the two limiting cases of vanishing magnetic field and vanishing temperature. For all other situations, numerical results provide evidence of a finite mutual information at all temperatures except at criticality. There, it diverges as the logarithm of the system size, with a prefactor that can take only two values, depending on whether the critical temperature vanishes or not. Our work provides a simple example in which the mutual information appears as a powerful tool to detect finite-temperature phase transitions, contrary to entanglement measures such as the concurrence.Comment: 12 pages, 9 figures, published versio

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Experimental signatures of the mixed axial-gravitational anomaly in the Weyl semimetal NbP

Weyl semimetals are materials where electrons behave effectively as a kind of massless relativistic particles known asWeyl fermions. These particles occur in two flavours, or chiralities, and are subject to quantum anomalies, the breaking of a conservation law by quantum fluctuations. For instance, the number of Weyl fermions of each chirality is not independently conserved in parallel electric and magnetic field, a phenomenon known as the chiral anomaly. In addition, an underlying curved spacetime provides a distinct contribution to a chiral imbalance, an effect known as the mixed axial-gravitational anomaly, which remains experimentally elusive. However, the presence of a mixed gauge-gravitational anomaly has recently been tied to thermoelectrical transport in a magnetic field, even in flat spacetime, opening the door to experimentally probe such type of anomalies in Weyl semimetals. Using a temperature gradient, we experimentally observe a positive longitudinal magnetothermoelectric conductance (PMTC) in the Weyl semimetal NbP for collinear temperature gradients and magnetic fields (DT || B) that vanishes in the ultra quantum limit. This observation is consistent with the presence of a mixed axial-gravitational anomaly. Our work provides clear experimental evidence for the existence of a mixed axial-gravitational anomaly of Weyl fermions, an outstanding theoretical concept that has so far eluded experimental detection

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: Is riboflavin supplementation effective?

Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and

Colour terms affect detection of colour and colour-associated objects suppressed from visual awareness

The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d’) and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object’s stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain

Friends and Foes from an Ant Brain's Point of View – Neuronal Correlates of Colony Odors in a Social Insect

Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ‘‘friend’’ and ‘‘foe’’ are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors