Using grounded theory to inform the design of energy interventions for the workplace

Much work has been published on using technological interventions to motivate reductions in home energy consumption. These interventions have produced promising results, but typically focus on emphasising the financial benefits of reductions in consumption to users. Motivating employees to reduce their consumption of energy in the workplace is more problematic, as they are typically not responsible for energy costs. There has been very little work to date addressing energy interventions in the workplace, and indeed, there are many challenges in doing so. This paper presents an overview of the initial user-centred design stage of a large energy research project called Electro-Magnates. Three day-long workshops were run with a total of 65 participants from 5 universities and a number of representatives from industry. The workshops’ main focus was understanding behaviour change in organisations in an energy resource and usage context, supported by designing a 12 month intervention. Audio and design task accounts were transcribed and analysed using the grounded theory approach with the developed theory forming the design requirements and implications for the Electro-Magnates intervention software. Our findings identified some of the key concepts for inclusion in a workplace energy intervention; incentivisation, openness and management buy-in

Utilizing aLIGO glitch classifications to validate gravitational-wave candidates

Advanced LIGO data contains numerous noise transients, or 'glitches', that have been shown to reduce the sensitivity of matched filter searches for gravitational waves from compact binaries. These glitches increase the rate at which random coincidences occur, which reduces the significance of identified gravitational-wave events. The presence of these transients has precipitated extensive work to establish that observed gravitational wave events are astrophysical in nature. We discuss the response of the PyCBC search for gravitational waves from stellar mass binaries to various common glitches that were observed during advanced LIGO's first and second observing runs. We show how these transients can mimic waveforms from compact binary coalescences and quantify the likelihood that a given class of glitches will create a trigger in the search pipeline. We explore the specific waveform parameters that are most similar to different glitch classes and demonstrate how knowledge of these similarities can be used when evaluating the significance of gravitational-wave candidates

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.Publisher PDFPeer reviewe

¹³CO and C¹⁸O observations of S140: delineation of the outflow structure, a study of fractionation effects and comparison with CI observations

The outflow and photon-dominated region (PDR) associated with the S140 complex have been observed at high resolution (~14 arcsec) in the 13CO and C18O J=3→2 lines. The C18O map confirms earlier C17O J=3→2line observations (Minchin et al. 1994) that show an `arc' of emission observed to the south of the peak, and also reveals a similar (and more prominent) arc feature to the east, a region not covered by the C17O map. This is a particularly fine example of the classic `tuning fork' morphology, where emission at the ambient cloud velocity is tracing the outflow cavity wall of the blueshifted lobe. The N(13CO)/N(C18O) ratio has been plotted against extinction and fits the power law relation N(13CO)/N(C18O)=21Av-0.35. The highest values, as expected, occur for observed positions towards the PDR, with N(13CO)/N(C18O) exceeding the terrestrial value (5.5) for Av ≤40 magnitudes. In the outermost parts of the cloud (Av ≤10 magnitudes) the N(13CO)/N(C18O) ratio is largest, up to 20. The increased fractionation may be due to higher photoionization of the optically thinner isotope, C18O. There is a close correlation between N(CI)/N(CO) and visual extinction over a wide extinction range (Av=3-100 mags.). The best fit power law is N(CI)/N(CO)=4.2Av0.9. For positions toward the outflow (Av~50-100) N(CI)/N(CO) ~0.1(0.07-0.12). N(CI)/N(CO) increases with decreasing extinction to ~1 for Av≤5 mags., corresponding to positions near the edge of the cloud. A detailed comparison of antenna temperatures and linewidths for the 13CO, C18O and CI lines is presented. The 13CO and C18O antenna temperatures and linewidths are closely correlated, and imply the emission, for both isotopes, emanates from gas that is in LTE and is well mixed. The CI emission from the PDR implies that here the atomic carbon is in LTE, but occupies a different volume of gas than the isotopic CO. Towards the outflow the CI linewidths are systematically broadened relative to those for the isotopic CO lines. This is interpreted as evidence that atomic carbon is produced by the effect of shocks on the chemical and physical processes at the interface between a stellar wind and the outflow cavity wall

Utilizing IgG1 Fc As An Immunomodulator

Antibody-based therapeutics are a rapidly expanding class of biopharmaceuticals. The number of approved antibody-based therapeutics by the FDA and EMA has more than doubled in the last five years, and they are expanding into areas such as antibody-drug conjugates, Fc fusions, bispecific antibodies, and biosimilars. Most antibody-based therapeutics use the Immunoglobulin isotype G subclass 1 (IgG1) antibody. Some IgG1-based therapeutics obtain their therapeutic efficacy by modulating the immune system for the treatment of several disease-types including cancer, autoimmune disease, and organ transplant rejection. This work further explores our understanding of IgG1-mediated immunomodulation by utilizing the fragment crystallizable (Fc) region of IgG1 in three research projects. In the first project, an IgG1 Fc fusion was prepared as a potential treatment for multiple sclerosis, an autoimmune disease that affects 2.3 million people worldwide. This disease involves immune system attack and destruction of the myelin protein surrounding the neurons in the central nervous system. One promising class of compounds that selectively prevent the activation of immune cells involved in the destruction of myelin are Bifunctional Peptide Inhibitors (BPIs). In an effort to further improve the bioactivity of BPIs, the BPI peptides were conjugated to the termini of IgG1 Fc to prepare a BPI-Fc fusion. This fusion was tested in a mouse model of multiple sclerosis. Compared to the PBS-treated control, mice treated with the BPI-Fc fusion showed significantly reduced disease symptoms, did not experience weight loss, and showed reduced demyelination. These results demonstrated that the BPI peptides were highly active at suppressing the disease when prepared as an Fc fusion. In the second project, the N-glycosylation of IgG1 Fc was modified. The N-glycosylation of IgG1 can markedly affect its function, stability, pharmacokinetics, solubility, and immunogenicity. However, recombinant expression of IgG1 results in a mixture of N-glycoforms. This heterogeneity makes it difficult to understand how N-glycosylation affects IgG1 because different N-glycoforms can affect the antibody differently. To solve this problem, this work utilized IgG1 Fc as a model system to prepare homogenous IgG1 Fc N-glycoforms, and their effects on IgG1 Fc were studied individually. In-vitro enzymatic synthesis was used to prepare homogenous oligomannose, hybrid, and complex N-glycoforms. The effect of each non-fucosylated N-glycoform on IgG1 Fc stability was compared using differential scanning calorimetry. The results showed that the complex N-glycoform was more stable than the hybrid and oligomannose N-glycoforms. Additionally, the effect of each N-glycoform on IgG1 Fc function was compared in an in-vitro receptor-binding assay using FcγRIIIa, the receptor involved in activating Antibody-dependent Cellular Cytotoxicity (ADCC). Results showed that the binding affinity increased with increased N-glycan processing. Lastly, the hybrid and complex IgG1 Fc N-glycoforms were compared for their abilities to accept core-linked fucose. Results showed that the complex N-glycoform accepted fucose much more slowly compared to the hybrid N-glycoforms. In the third project, IgG1 Fc was assembled as a protein-polymer conjugate in order to increase its valency. Multivalent display of IgG1 is necessary in order to obtain an avidity effect strong enough to activate immune system effector functions, such as ADCC. IgG1 Fc-polymer conjugate was prepared using controlled polymerization to first synthesize a water soluble, linear poly(acrylamide-peptide) co-polymer. This co-polymer was then used as a scaffold onto which multiple IgG1 Fc proteins were site-specifically ligated. The IgG1 Fc-polymer conjugate was compared against IgG1 Fc in a receptor binding assay with FcγRIIIa. The results showed that the IgG1 Fc-polymer conjugate bound FcγRIIIa 800 times stronger compared to free IgG1 Fc. This large increase in binding strength was caused by the multimer having a much slower dissociation rate. The research presented in this dissertation improves our fundamental understanding IgG1-mediated immunomodulation and may also help in the development of improved antibody- based therapeutics