engineering-platform-experimental-protocol-for-design-evaluation

Engineering Platform and Experimental Protocol for Design and Evaluation of a Neurally-controlled Powered Transfemoral Prosthesis

To enable intuitive operation of powered artificial legs, an interface between user and prosthesis that can recognize the user's movement intent is ...

University of North Carolina School of Medicine

Atlantic Prosthetics & Orthotics, LLC

This paper surveys some recent developments in media criticism and recent developments in film and media representations of mental distress. Focusing on a representations drawn from various forms of media, the paper argues that media and film images of mental distress are in many cases 'positive' and sympathetic, although they can also contain sexist, racist and other problematic elements that are not commonly identified by anti-stigma campaigners. It also suggests that while still valid in many ways, existing anti-stigma criticism tends to focus on a rather undifferentiated notion of 'violence to others' as the sole criterion against which media images are judged. Finally, the paper proposes that critics and campaigners pay closer attention to how the particular form or genre of any media text influences its treatment of psychological distress.

Understanding mental distress in film and media: a new agenda?

The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets.

Adaptation and validation of the Charlson Index for Read/OXMIS coded databases.

Incorporation of organic waste amendments to a horticultural soil, prior to expected risk periods, could immobilise mineral N, ultimately reducing nitrogen (N) losses as nitrous oxide (N(2)O) and leaching. Two organic waste amendments were selected, a fresh green waste (FGW) and green waste compost (GWC) as they had suitable biochemical attributes to initiate N immobilisation into the microbial biomass and organic N forms. These characteristics include a high C:N ratio (FGW 44:1, GWC 35:1), low total N (<1%), and high lignin content (>14%). Both products were applied at 3t C/ha to a high N (plus N fertiliser) or low N (no fertiliser addition) Vertisol soil in PVC columns. Cumulative N(2)O production over the 28 day incubation from the control soil was 1.5mg/N(2)O/m(2), and 11mg/N(2)O/m(2) from the control+N. The N(2)O emission decreased with GWC addition (P<0.05) for the high N soil, reducing cumulative N(2)O emissions by 38% by the conclusion of the incubation. Analysis of mineral N concentrations at 7, 14 and 28 days identified that both FGW and GWC induced microbial immobilisation of N in the first 7 days of incubation regardless of whether the soil environment was initially high or low in N; with the FGW immobilising up to 30% of available N. It is likely that the reduced mineral N due to N immobilisation led to a reduced substrate for N(2)O production during the first week of the trial, when soil N(2)O emissions peaked. An additional finding was that FGW+N did not decrease cumulative N(2)O emissions compared to the control+N, potentially due to the fact that it stimulated microbial respiration resulting in anaerobic micro sites in the soil and ultimately N(2)O production via denitrification. Therefore, both materials could be used as post harvest amendments in horticulture to minimise N loss through nitrate-N leaching in the risk periods between crop rotations. The mature GWC has potential to reduce N(2)O, an important greenhouse gas.

Effect of fresh green waste and green waste compost on mineral nitrogen, nitrous oxide and carbon dioxide from a Vertisol.

Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily.

Structure of the USP15 N-terminal domains: a β-hairpin mediates close association between the DUSP and UBL domains.

To report a case of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus (SLE) successfully treated with plasma exchange and rituximab

Plasma exchange and rituximab in the management of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus.

The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains.

Lactate dehydrogenase A (LDH-A) is a key enzyme in anaerobic respiration that is predominantly found in skeletal muscle and catalyses the reversible conversion of pyruvate to lactate in the presence of NADH. LDH-A is overexpressed in many tumours and has therefore emerged as an attractive target for anticancer drug discovery. Crystal structures of human LDH-A in the presence of inhibitors have been described, but currently no structures of the apo or binary NADH-bound forms are available for any mammalian LDH-A. Here, the apo structure of human LDH-A was solved at a resolution of 2.1 Å in space group P4122. The active-site loop adopts an open conformation and the packing and crystallization conditions suggest that the crystal form is suitable for soaking experiments. The soaking potential was assessed with the cofactor NADH, which yielded a ligand-bound crystal structure in the absence of any inhibitors. The structures show that NADH binding induces small conformational changes in the active-site loop and an adjacent helix. A comparison with other eukaryotic apo LDH structures reveals the conservation of intra-loop interactions. The structures provide novel insight into cofactor binding and provide the foundation for soaking experiments with fragments and inhibitors.

Stephen Harper

Department of Physical Medicine and Rehabilitation

University of North Carolina School of Medicine

Engineering Platform and Experimental Protocol for Design and Evaluation of a Neurally-controlled Powered Transfemoral Prosthesis