Intercomparison of stratospheric chemistry models under polar vortex conditions

Several stratospheric chemistry modules from box, 2-D or 3-D models, have been intercompared. The intercomparison was focused on the ozone loss and associated reactive species under the conditions found in the cold, wintertime Arctic and Antarctic vortices. Comparisons of both gas phase and heterogeneous chemistry modules show excellent agreement between the models under constrained conditions for photolysis and the microphysics of polar stratospheric clouds. While the mean integral ozone loss ranges from 4-80% for different 30-50 days long air parcel trajectories, the mean scatter of model results around these values is only about +/-1.5%. In a case study, where the models employed their standard photolysis and microphysical schemes, the variation around the mean percentage ozone loss increases to about +/-7%. This increased scatter of model results is mainly due to the different treatment of the PSC microphysics and heterogeneous chemistry in the models, whereby the most unrealistic assumptions about PSC processes consequently lead to the least representative ozone chemistry. Furthermore, for this case study the model results for the ozone mixing ratios at different altitudes were compared with a measured ozone profile to investigate the extent to which models reproduce the stratospheric ozone losses. It was found that mainly in the height range of strong ozone depletion all models underestimate the ozone loss by about a factor of two. This finding corroborates earlier studies and implies a general deficiency in our understanding of the stratospheric ozone loss chemistry rather than a specific problem related to a particular model simulation

The multiphase gas structure and kinematics in the circumnuclear region of NGC 5728

We report on our combined analysis of HST, VLT/MUSE, VLT/SINFONI, and ALMA observations of the local Seyfert 2 galaxy, NGC 5728 to investigate in detail the feeding and feedback of the active galactic nucleus (AGN). The data sets simultaneously probe the morphology, excitation, and kinematics of the stars, ionized gas, and molecular gas over a large range of spatial scales (10 pc to 10 kpc). NGC 5728 contains a large stellar bar that is driving gas along prominent dust lanes to the inner 1 kpc where the gas settles into a circumnuclear ring. The ring is strongly star forming and contains a substantial population of young stars as indicated by the lowered stellar velocity dispersion and gas excitation consistent with H II regions. We model the kinematics of the ring using the velocity field of the CO (2–1) emission and stars and find it is consistent with a rotating disc. The outer regions of the disc, where the dust lanes meet the ring, show signatures of inflow at a rate of 1 M⊙ yr−1. Inside the ring, we observe three molecular gas components corresponding to the circular rotation of the outer ring, a warped disc, and the nuclear stellar bar. The AGN is driving an ionized gas outflow that reaches a radius of 250 pc with a mass outflow rate of 0.08 M⊙ yr−1 consistent with its luminosity and scaling relations from previous studies. While we observe distinct holes in CO emission which could be signs of molecular gas removal, we find that largely the AGN is not disrupting the structure of the circumnuclear region

Precise determination of the low-energy electronuclear Hamiltonian of LiY1−x HoxF4

The insulating rare-earth magnet LiY1−xHoxF4 has received great attention because a laboratory field applied perpendicular to its crystallographic c axis converts the low-energy electronic spin Hamiltonian into the (dilute) transverse field Ising model. The mapping between the real magnet and the transverse field Ising model is strongly dependent on the exact nature of the low-energy Hamiltonian for the material, which can be determined by spectroscopy in the dilute limit. The energies of the eigenstates are in the difficult terahertz (THz) regime, and here we use THz time domain and Fourier transform spectroscopy to directly measure the lowest crystal-field levels of LiY1−xHoxF4 in the dilute limit, including nuclear hyperfine substructure. The high resolution of our measurements allows us to observe the nonequidistantly spaced Ho (I = 72 ) hyperfine transitions originating from dipolar and quadrupolar hyperfine interactions. We provide refined crystal-field parameters and extract the dipolar and quadrupolar hyperfine constants AJ = 0.027 03 ± 0.000 03 cm−1 (810.3 ± 0.9 MHz) and B = 0.04 ± 0.01 cm−1(1.2 ± 0.3 GHz), respectively. Thereupon we determine all crystal-field energy levels and magnetic moments of the 5/8 ground-state manifold, including the (nonlinear) hyperfine corrections. The latter improve the prediction precision by a factor of 60 compared to previous crystal-field parameters. Additionally,we establish the far-infrared, low-temperature refractive index of LiY1−xHoxF4

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

OBJECTIVE: We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. MATERIALS AND METHODS: We selected patients who suffered with UIP (n = 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. RESULTS: The amount of anterior mediastinal fat was not different among the three groups (p = 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-infinity, p < 0.001) and UIP (OR = 24.42, CI 4.06-infinity, p < 0.001). CONCLUSION: For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat.This study is supported by KISTEP, the Ministry of Science and Technology, Korea

Gaze following is modulated by expectations regarding others’ action goals

Humans attend to social cues in order to understand and predict others' behavior. Facial expressions and gaze direction provide valuable information to infer others' mental states and intentions. The present study examined the mechanism of gaze following in the context of participants' expectations about successive action steps of an observed actor. We embedded a gaze-cueing manipulation within an action scenario consisting of a sequence of naturalistic photographs. Gaze-induced orienting of attention (gaze following) was analyzed with respect to whether the gaze behavior of the observed actor was in line or not with the action-related expectations of participants (i.e., whether the actor gazed at an object that was congruent or incongruent with an overarching action goal). In Experiment 1, participants followed the gaze of the observed agent, though the gaze-cueing effect was larger when the actor looked at an action-congruent object relative to an incongruent object. Experiment 2 examined whether the pattern of effects observed in Experiment 1 was due to covert, rather than overt, attentional orienting, by requiring participants to maintain eye fixation throughout the sequence of critical photographs (corroborated by monitoring eye movements). The essential pattern of results of Experiment 1 was replicated, with the gaze-cueing effect being completely eliminated when the observed agent gazed at an action-incongruent object. Thus, our findings show that covert gaze following can be modulated by expectations that humans hold regarding successive steps of the action performed by an observed agent

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines

Recurrent chromosome breakpoints in tumour cells may point to cancer genes, but not many have been molecularly characterised. We have used multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) on breast tumour cell lines to identify regions of chromosome break created by inversions, duplications, insertions and translocations on chromosomes 1, 5, 8, 12 and 17. We delineate a total of 136 regions of break, some of them occurring with high frequency. We further describe two examples of dual-colour FISH characterisation of breakpoints, which target the 1p36 and 5p11–12 regions. Both breaks involve genes whose function is unknown to date. The mbanding-FISH strategy constitutes an efficient first step in the search for potential cancer genes