Direct observation of impurity-induced magnetism in an S = 1/2 antiferromagnetic Heisenberg 2-leg spin ladder

Nuclear magnetic resonance and magnetization measurements were used to probe the magnetic features of single-crystalline Bi(Cu(1-x)Znx)2PO6 with 0<x<0.05 at temperatures between 2.6 K and 300 K. The simple lineshape of the 31P NMR signals of the pristine compound changes considerably for x>0 and we present clear evidence for a temperature dependent variation of the local magnetization close to the Zn sites. The generic nature of this observation is indicated by results of model calculations on appropriate spin systems of limited size employing QMC methods.Comment: 4 pages, 4 figure

Two Coupled Chains are Simpler than One: Field-induced Chirality in a Frustrated Quantum Spin Ladder

Although the frustrated spin chain (zigzag chain) is a Drosophila of frustrated magnetism, the understanding of a pair of coupled zigzag chains (frustrated spin ladder) in a magnetic field is incomplete. We address this problem through nuclear magnetic resonance (NMR) experiments on $\text{BiCu}_2\text{PO}_6$ in magnetic fields up to 45 T, revealing a field-induced spiral magnetic structure. Conjointly, we present advanced numerical calculations showing that even moderate rung coupling dramatically simplifies the phase diagram below half-saturation magnetization by stabilizing a field-induced chiral phase. Surprisingly for a one-dimensional model, this phase and its response to Dzyaloshinskii-Moriya (DM) interactions adhere to classical expectations. While explaining the behavior at the highest accessible magnetic fields, our results imply a different origin for the solitonic phases occurring at lower fields in $\text{BiCu}_2\text{PO}_6$. An exciting possibility is that the known, DM-mediated coupling between chirality and crystal lattice gives rise to a new kind of spin-Peierls instability.Comment: Revised manuscript, 7 pages, 6 figure

Human Metapneumovirus Glycoprotein G Inhibits Innate Immune Responses

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infection in infants, as well as in the elderly and immunocompromised patients. No effective treatment or vaccine for hMPV is currently available. A recombinant hMPV lacking the G protein (rhMPV-ΔG) was recently developed as a potential vaccine candidate and shown to be attenuated in the respiratory tract of a rodent model of infection. The mechanism of its attenuation, as well as the role of G protein in modulation of hMPV-induced cellular responses in vitro, as well as in vivo, is currently unknown. In this study, we found that rhMPV-ΔG-infected airway epithelial cells produced higher levels of chemokines and type I interferon (IFN) compared to cells infected with rhMPV-WT. Infection of airway epithelial cells with rhMPV-ΔG enhanced activation of transcription factors belonging to the nuclear factor (NF)-κB and interferon regulatory factor (IRF) families, as revealed by increased nuclear translocation and/or phosphorylation of these transcription factors. Compared to rhMPV-WT, rhMPV-ΔG also increased IRF- and NF-κB-dependent gene transcription, which was reversely inhibited by G protein expression. Since RNA helicases have been shown to play a fundamental role in initiating viral-induced cellular signaling, we investigated whether retinoic induced gene (RIG)-I was the target of G protein inhibitory activity. We found that indeed G protein associated with RIG-I and inhibited RIG-I-dependent gene transcription, identifying an important mechanism by which hMPV affects innate immune responses. This is the first study investigating the role of hMPV G protein in cellular signaling and identifies G as an important virulence factor, as it inhibits the production of important immune and antiviral mediators by targeting RIG-I, a major intracellular viral RNA sensor

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

OBJECTIVES: Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice. METHODS: Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator's current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009). RESULTS: 63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer's GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice. CONCLUSION: There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers

A Spatially Resolved Dark- versus Light-Zone Microenvironment Signature Subdivides Germinal Center-Related Aggressive B Cell Lymphomas

We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZ mutational machinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit (DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were subclassified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas

Incidental findings found in "healthy" volunteers during imaging performed for research: current legal and ethical implications

Incidental findings found in “healthy” volunteers during research imaging are common and have important implications for study design and performance, particularly in the areas of informed consent, subjects' rights, clinical image analysis and disclosure. In this study, we aimed to determine current practice and regulations concerning information that should be given to research subjects when obtaining consent, reporting of research images, who should be informed about any incidental findings and the method of disclosure. We reviewed all UK, European and international humanitarian, legal and ethical agencies' guidance. We found that the guidance on what constitutes incidental pathology, how to recognise it and what to do about it is inconsistent between agencies, difficult to find and less complete in the UK than elsewhere. Where given, guidance states that volunteers should be informed during the consent process about how research images will be managed, whether a mechanism exists for identifying incidental findings, arrangements for their disclosure, the potential benefit or harm and therapeutic options. The effects of incidentally discovered pathology on the individual can be complex and far-reaching. Radiologist involvement in analysis of research images varies widely; many incidental findings might therefore go unrecognised. In conclusion, guidance on the management of research imaging is inconsistent, limited and does not address the interests of volunteers. Improved standards to guide management of research images and incidental findings are urgently required

Human Metapneumovirus Inhibits IFN-β Signaling by Downregulating Jak1 and Tyk2 Cellular Levels

Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses

Supporting Users in Cloud Plan Selection

Cloud computing is a key technology for outsourcing data and applications to external providers. The current cloud market offers a multitude of solutions (plans) differing from one another in terms of their characteristics. In this context, the selection of the right plan for outsourcing is of paramount importance for users wishing to move their data/applications to the cloud. The scientific community has then developed different models and tools for capturing users\u2019 requirements and evaluating candidate plans to determine the extent to which each of them satisfies such requirements. In this chapter, we illustrate some of the existing solutions proposed for cloud plan selection and for supporting users in the specification of their (crisp and/or fuzzy) needs