Mapping the optical absorption of a substrate-transferred crystalline AlGaAs coating at 1.5 µm

The sensitivity of 2nd and 3rd generations of interferometric gravitational wave detectors will be limited by thermal noise of the test-mass mirrors and highly reflective coatings. Recently developed crystalline coatings show a promising thermal noise reduction compared to presently used amorphous coatings. However, stringent requirements apply to the optical properties of the coatings as well. We have mapped the optical absorption of a crystalline AlGaAs coating which is optimized for high reflectivity for a wavelength of 1064nm. The absorption was measured at 1550nm where the coating stack transmits approximately 70% of the laser light. The measured absorption was lower than (30.2 +/- 11.1)ppm which is equivalent to (3.6 +/- 1.3)ppm for a coating stack that is highly reflective at 1530nm. While this is a very promising low absorption result for alternative low--loss coating materials, further work will be necessary to reach the requirements of <1ppm for future gravitational wave detectors. Jessica Steinlechner, Iain W Martin, Angus Bell, Garrett Cole, Jim Hough, Steven Penn, Sheila Rowan, Sebastian Steinlechne

Obstacle course: Users’ maneuverability and movement efficiency when using Otto Bock C-Leg, Otto Bock 3R60, and CaTech SNS prosthetic knee joints

The performance and movement efficiency of prosthesis users while traversing a multisectional obstacle course (OC) were evaluated using a crossover design with random allocation of three prosthetic knee joints: the SNS (CaTech; Dayton, Ohio) the C-Leg (Otto Bock; Duderstadt, Germany), and the 3R60 (Otto Bock). Twelve users completed the OC twice with each joint, once without and once with a mental loading task (MLT). The performance was objectively assessed using time measurement from digital video recordings, and the Total Heart Beat Index was used to estimate movement efficiency. A 1 mo familiarization period was provided for each knee joint before data collection. It took longer to complete the OC with the 3R60 compared with either the SNS or the C-Leg. No significant time differences were found between the C-Leg and the SNS, but differences between the 3R60 and the SNS (slalom and rock sections) and between the 3R60 and the C-Leg (rock section) were observed. Within the simulated sand section, two participants fell with the C-Leg, one with the 3R60, and none with the SNS. Movement efficiency without MLT was similar between all joints, but with an MLT a significant decrease in movement efficiency was observed with the C-Leg. Previous experience using an SNS had no influence on the results

Identifying key areas for active interprofessional learning partnerships:a facilitated dialogue

Student and service user involvement is recognised as an important factor in creating interprofessional education (IPE) opportunities. We used a team-based learning approach to bring together undergraduate health professional students, early career professionals (ECPs), public partners, volunteers, and carers to explore learning partnerships. Influenced by evaluative inquiry, this qualitative study used a free text response to allow participants to give their own opinion. A total of 153 participants (50 public partners and 103 students and professionals representing 11 healthcare professions) took part. Participants were divided into mixed groups of six (n = 25) and asked to identify areas where students, professionals, and public could work together to improve health professional education. Each group documented their discussions by summarising agreed areas and next steps. Responses were collected and transcribed for inductive content analysis. Seven key themes (areas for joint working) were identified: communication, public as partners, standards of conduct, IPE, quality improvement, education, and learning environments. The team-based learning format enabled undergraduate and postgraduate health professionals to achieve consensus with public partners on areas for IPE and collaboration. Some of our results may be context-specific but the approach is generalisable to other areas.</p

The status of Habitats Directive Annex I saltmarsh habitats, transition zones and spartina species in England

On unmodified soft sediment coastlines, of which there are long lengths especially on the English east and south coasts, there should be a wide transitional zone between tidal areas and full terrestrial land. The conditions in this zone result in a rich and distinctive range of habitats. There are two saltmarsh habitats listed in Annex I of the Habitats Directive within this zone (H1420 Mediterranean and thermo-Atlantic halophilous scrubs and H1320 Spartina swards,Spartinion maritimae) reflecting its importance for nature conservation. At the time work for this project was started in 2012, the conservation status of these habitats was reported as ‘unfavourable, bad and deteriorating’. Due to construction of artificial sea defences, these zones are now much reduced in extent and distribution and are under threat from a range of factors. This project aims to provide an inventory and description of Annex I saltmarsh habitats and transitional vegetation in England. This will help to update future reporting on conservation status. The outcomes will also help improve understanding of the underpinning processes which can be used in design to improve the potential for recreating these elements of saltmarshes as part of intertidal restoration schemes. The project also provides an up to date assessment of Spartina alterniflora stands in the Solent SAC through review and field survey for 2012

Functional network changes and cognitive control in schizophrenia

Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness

A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas

Schwannomas are common, highly morbid and medically untreatable tumors that can arise in patients with germ line as well as somatic mutations in neurofibromatosis type 2 (NF2). These mutations most commonly result in the loss of function of the NF2-encoded protein, Merlin. Little is known about how Merlin functions endogenously as a tumor suppressor and how its loss leads to oncogenic transformation in Schwann cells (SCs). Here, we identify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-inducing kinase (NIK) as a potential drug target driving NF-κB signaling and Merlin-deficient schwannoma genesis. Using a genomic approach to profile aberrant tumor signaling pathways, we describe multiple upregulated NF-κB signaling elements in human and murine schwannomas, leading us to identify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-κB signaling. Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, survival, and adhesion while inducing schwannoma formation in a novel in vivo orthotopic transplant model. Furthermore, we describe an NF-κB-potentiated hepatocyte growth factor (HGF) to MET proto-oncogene receptor tyrosine kinase (c-Met) autocrine feed-forward loop promoting SC proliferation. These innovative studies identify a novel signaling axis underlying schwannoma formation, revealing new and potentially druggable schwannoma vulnerabilities with future therapeutic potential

Agrarstruktur in Ghandruk und Umgebung : Schwerpunkt Ackerbau und Hausgärten

Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro.We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted

Non-random escape pathways from a broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412-423

A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412-423 is conserved and antibodies to 412-423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412-423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412-423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities