Role of Peptide Backbone Conformation on Biological Activity of Chemotactic Peptides

To investigate the role of peptide backbone conformation on the biological activity of chemotactic peptides, we synthesized a unique analog of N-formyl-Met-Leu-Phe-OH incorporating the C α,α disubstituted residue, dipropylglycine (Dpg) in place of Leu. The conformation of the stereochemically constrained Dpg analog was examined in the crystalline state by x-ray diffraction and in solution using NMR, IR, and CD methods. The secretagogue activity of the peptide on human neutrophils was determined and compared with that of a stereochemically constrained, folded type II β-turn analog incorporating 1-aminocyclohexanecarboxylic acid (Ac6c) at position 2 (f-Met- Ac6c -Phe-OMe), the parent peptide (f-Met-Leu-Phe-OH) and its methyl ester derivative (f-Met-Leu-Phe-OMe). In the solid state, the Dpg analog adopts an extended β-sheet-like structure with an intramolecular hydrogen bond between the NH and CO groups of the Dpg residue, thereby forming a fully extended (C5) conformation at position 2. The ϕ and ψ values for Met and Phe residues are significantly lower than the values expected for an ideal antiparallel beta conformation causing a twist in the extended backbone both at the N and C termini. Nuclear magnetic resonance studies suggest the presence of a significant population of the peptide molecules in an extended antiparallel β conformation and the involvement of Dpg NH in a C5 intramolecular hydrogen bond in solutions of deuterated chloroform and deuterated dimethyl sulfoxide. IR studies provide evidence for the presence of an intramolecular hydrogen bond in the molecule and the antiparallel extended conformation in chloroform solution. CD spectra in methanol, trifluoroethanol, and trimethyl phosphate indicate that the Dpg peptide shows slight conformational flexibility, whereas the folded Ac6c analog is quite rigid. The extended Dpg peptide consistently shows the highest activity in human peripheral blood neutrophils, being approximately 8 and 16 times more active than the parent peptide and the folded Ac6c analog, respectively. However, the finding that all four peptides have ED50 (the molar concentration of peptide to induce half-maximal enzyme release) values in the 10(-8)-10(-9) M range suggests that an induced fit mechanism may indeed be important in this ligand-receptor interaction. Moreover, it is also possible that alterations in the backbone conformation at the tripeptide level may not significantly alter the side chain topography and/or the accessibility of key functional groups important for interaction with the receptor

Can vectors read minds better than experts? Comparing data augmentation strategies for the automated scoring of children's mindreading ability

In this paper we implement and compare 7 different data augmentation strategies for the task of automatic scoring of children's ability to understand others' thoughts, feelings, and desires (or "mindreading"). We recruit in-domain experts to re-annotate augmented samples and determine to what extent each strategy preserves the original rating. We also carry out multiple experiments to measure how much each augmentation strategy improves the performance of automatic scoring systems. To determine the capabilities of automatic systems to generalize to unseen data, we create UK-MIND-20 - a new corpus of children's performance on tests of mindreading, consisting of 10,320 question-answer pairs. We obtain a new state-of-the-art performance on the MIND-CA corpus, improving macro-F1-score by 6 points. Results indicate that both the number of training examples and the quality of the augmentation strategies affect the performance of the systems. The task-specific augmentations generally outperform task-agnostic augmentations. Automatic augmentations based on vectors (GloVe, FastText) perform the worst. We find that systems trained on MIND-CA generalize well to UK-MIND-20. We demonstrate that data augmentation strategies also improve the performance on unseen data.Comment: The paper will be presented at ACL-IJCNLP 202

Physiotherapy Students’ Attitudes Toward Working With People With Dementia: A Cross-Sectional Survey

Aims: To understand personal, educational and clinical experiences and the attitudes of physiotherapy students towards people with dementia. Methods: Online survey questionnaire. Physiotherapy students in the last year of a two-year Masters of Physical Therapy (MPT) entry-to-practice degree program (n = 59) were surveyed. Descriptive statistics were used to analyze the data. Results: Fifty-five students participated (93%). The majority of students (n = 52/55, 77%) had at least one clinical placement working with people with dementia. Overall, 53% (n = 29/55) felt their academic training was sufficient to effectively work with people with dementia. Moreover, 82% (n = 45/55) reported their confidence was greatest working with people who could communicate well verbally. Conclusions: Disease-based knowledge was strong, yet just over half felt their academic training was sufficient to effectively work with people with dementia. The findings support the need for more training, particularly in communication strategies, to support students to effectively work with client with dementia upon graduation

The effect of Demand Response and wind generation on electricity investment and operation. ESRI WP577, December 2017

We present a novel method of determining the contribution of load-shifting Demand Response (DR) to energy and reserve markets. We model DR in an Mixed Complementarity Problem (MCP) framework with high levels of wind penetration. Investment, exit and operational decisions are optimised simultaneously. We examine the potential for DR to participate in both energy and reserve markets. DR participation in the energy market reduces costs and prices but the impact of DR participation in reserve markets is limited. DR and wind generation are strongly complementary, due to the ability of DR to mitigate against the variability of wind generation, with the highest impacts of DR seen at high levels of wind penetration. DR participation in the energy market gives rise to lower equilibrium levels of investment in conventional generation and induces a Pareto improvement versus a market with no DR participation. The total impact of DR is highly dependent on specific system characteristics

The effect of Demand Response and wind generation on electricity investment and operation. ESRI Research Bulletin 2019/07

Concerns over climate change have led to an increase in renewable energy usage, particularly in the electricity sector. Given that the output from many renewable sources of energy, such as wind and solar, increases and decreases throughout the course of a day or week, there is a greater requirement for the rest of the electricity system to behave flexibly as renewable energy increases. Traditionally, electricity demand was considered fixed and power generation units, such as coal, gas and oil units, varied their supply to match supply and demand in realtime. However in recent years, there has been a new focus on the potential for electricity demand itself to become flexible or responsive by means of households and businesses increasing their electricity usage at times of high availability, and decreasing their usage at times of low availability

The impacts of demand response participation in capacity markets. ESRI Research Bulletin 2019/10

Electricity demand varies over the course of a day or a year, with very high levels of electricity demand being seen for only a few hours per year. However, there must be sufficient electricity generation installed on the system to meet the total demand at these few hours per year, in order to avoid blackouts or brownouts, where electricity supply is disconnected for all or some customers, respectively. As electricity generation from variable renewable sources, such as wind and solar, increases, electricity market revenues decrease, which renders conventional generators less profitable. In order to ensure that there is sufficient conventional generation available to meet demand at the hours of highest demand per year, a separate market payment is made to generators, called a capacity payment

"What is on your mind?" Automated Scoring of Mindreading in Childhood and Early Adolescence

In this paper we present the first work on the automated scoring of mindreading ability in middle childhood and early adolescence. We create MIND-CA, a new corpus of 11,311 question-answer pairs in English from 1,066 children aged 7 to 14. We perform machine learning experiments and carry out extensive quantitative and qualitative evaluation. We obtain promising results, demonstrating the applicability of state-of-the-art NLP solutions to a new domain and task.Comment: Accepted in COLING 202

The opioid crisis fuelled by health systems: how will future physicians fare?

The opioid crisis continues to affect many areas worldwide, raising questions regarding prescribing indications. There is no consensus on negotiating the need for pain relief and the potential for medically prescribed opioid-related harm/addiction. These issues present an enormous educational challenge to physicians in training, particularly those whose mandate is to understand and respond to varying forms of pain. This article examines the perspectives and educational challenges faced by two psychiatry residents from different parts of the globe during the crisis. Is the educational experience of future psychiatrists sufficient to prepare them for the responsibilities that lie ahead