Synthesis of Glycopharmaceuticals for the Treatment of Microbial sepsis

Carbohydrates (glycans) form the basis of all living organisms and, consequently, are ubiquitous both in nature as biologically active compounds and in medicine as pharmaceuticals. One important application of carbohydrate-based drugs (glycopharmaceuticals) is the treatment of microbial sepsis, an acute illness that causes 100,000+ human deaths annually in the US alone. Exposure of the patient’s blood system to E. coli bacteria causes a massive, and often fatal, immune response. One important cellular receptor that senses the bacterium and is critically involved in triggering the immune response is CD14. Significant efforts by our team and others have been made to develop carbohydrate-based drugs called anti-microbial antagonists that target and block the CD14 receptor, thus terminating the infection/immune response cascade. Nevertheless, microbial sepsis remains a long-standing, difficult-to-solve problem that requires innovative approaches since progress in this unmet medical need has been difficult to achieve. Among new promising developments is antagonist AM-12 that is an attractive drug candidate due to its relatively simple structure, stability, potent activity, and lack of toxicity, discovered by Drs. Demchenko and Nichols (UMSL). To capitalize on this discovery of this promising anti-microbial receptor antagonist and extend this development to new therapeutic avenues, my project aims to develop a range of novel carbohydrate-derived drugs. At the completion of this projects, my synthetic compounds with superior pharmaceutical properties will help to accelerate discovery in many scientific disciplines with significant public health impact

Student voices in academic writing: PsychLiverpool a community for meaning making

The practice and expectations of academic communication are changing and blogging provides a socially liberating mechanism through which to support the development of student writing and literacy. The study reported here examines the impact of an academic–student partnership in supporting the development of student discourse. Anonymous feedback gathered from both the contributors and readers of the student blog, PsychLiverpool, was analysed using automated text analysis. The analysis identified that high levels of positive emotion were associated with PsychLiverpool. Students valued its capacity to trigger thinking and insight, and the social and networking relationships the blog offered. PsychLiverpool empowered students to expand their learning networks outside their classroom and to peer-network by connecting them with like-minded students and academics. By providing students with safe opportunities to develop their skills and networks, it fulfilled their needs for affiliation and achievement, power, and reward. The particular advantage of PsychLiverpool was that in operating outside traditional university processes of assessment and feedback, students were more motivated to write about and engage with academic language on their own terms

Revisiting Rossion and Pourtois with new ratings for automated complexity, familiarity, beauty, and encounter

Differences between norm ratings collected when participants are asked to consider more than one picture characteristic are contrasted with the traditional methodological approaches of collecting ratings separately for image constructs. We present data that suggest that reporting normative data, based on methodological procedures that ask participants to consider multiple image constructs simultaneously, could potentially confounded norm data. We provide data for two new image constructs, beauty and the extent to which participants encountered the stimuli in their everyday lives. Analysis of this data suggests that familiarity and encounter are tapping different image constructs. The extent to which an observer encounters an object predicts human judgments of visual complexity. Encountering an image was also found to be an important predictor of beauty, but familiarity with that image was not. Taken together, these results suggest that continuing to collect complexity measures from human judgments is a pointless exercise. Automated measures are more reliable and valid measures, which are demonstrated here as predicting human preferences.Published versio

What paint can tell us: A fractal analysis of neurological changes in seven artists

Objective: The notion that artistic capability increases with dementia is both novel and largely unsupported by available literature. Recent research has suggested an emergence of artistic capabilities to be a by-product of involuntary behaviour seen with dementia, as opposed to a progression in original thinking (de Souza, et al., 2010). A far more complementary explanation comes from Hannemann (2006), who suggests that art offers an outlet for dementia patients to refine and sharpen their cognitive abilities. As dementia severely impedes linguistic skills, non-verbal therapeutic methods such as painting can permit dementia patients to express themselves in a way not possible verbally. Fractal analysis has been used to determine the authenticity of major works of art. Taylor et al., (1999) found that through a fractal analysis of Jackson Pollock’s paintings it was possible to distinguish authentic works from a large collection of fakes, demonstrating that when artists paint they instill within their work their own pattern of unique fractal behaviour. Can age-indexed variations in the fractal dimension of the works of artists anticipate specific cognitive deteriorations? Method: To answer this question we analysed age-related variations in the fractal dimension of a large corpus of digital images (n⫽2092) of work created by seven notable artists who experienced both normal ageing and neurodegenerative disorders. Results: The results of our analysis showed that patterns of change in the fractal dimension of the paintings differentiated artists who suffered neurological deterioration from those of normal aging controls. Conclusions: These findings are of importance for two reasons. Our work adds to studies that demonstrate that fractal analysis has the potential to determine the provenance of paintings. Secondly, our work suggests that may be possible to identify a-typical changes in the structure of an artist’s work; changes that may be early indicators of the onset of neurological deterioration

Evaluating 'Prefer not to say' Around Sensitive Disclosures

As people's offline and online lives become increasingly entwined, the sensitivity of personal information disclosed online is increasing. Disclosures often occur through structured disclosure fields (e.g., drop-down lists). Prior research suggests these fields may limit privacy, with non-disclosing users being presumed to be hiding undesirable information. We investigated this around HIV status disclosure in online dating apps used by men who have sex with men. Our online study asked participants (N=183) to rate profiles where HIV status was either disclosed or undisclosed. We tested three designs for displaying undisclosed fields. Visibility of undisclosed fields had a significant effect on the way profiles were rated, and other profile information (e.g., ethnicity) could affect inferences that develop around undisclosed information. Our research highlights complexities around designing for non-disclosure and questions the voluntary nature of these fields. Further work is outlined to ensure disclosure control is appropriately implemented around online sensitive information disclosures

Astroglial d-serine is the endogenous co-agonist at the presynaptic NMDA receptor in rat entorhinal cortex

Presynaptic NMDA receptors facilitate the release of glutamate at excitatory cortical synapses and are involved in regulation of synaptic dynamics and plasticity. At synapses in the entorhinal cortex these receptors are tonically activated and provide a positive feedback modulation of the level of background excitation. NMDA receptor activation requires obligatory occupation of a co-agonist binding site, and in the present investigation we have examined whether this site on the presynaptic receptor is activated by endogenous glycine or d-serine. We used whole-cell patch clamp recordings of spontaneous AMPA receptor-mediated synaptic currents from rat entorhinal cortex neurones in vitro as a monitor of presynaptic glutamate release. Addition of exogenous glycine or d-serine had minimal effects on spontaneous release, suggesting that the co-agonist site was endogenously activated and likely to be saturated in our slices. This was supported by the observation that a co-agonist site antagonist reduced the frequency of spontaneous currents. Depletion of endogenous glycine by enzymatic breakdown with a bacterial glycine oxidase had little effect on glutamate release, whereas d-serine depletion with a yeast d-amino acid oxidase significantly reduced glutamate release, suggesting that d-serine is the endogenous agonist. Finally, the effects of d-serine depletion were mimicked by compromising astroglial cell function, and this was rescued by exogenous d-serine, indicating that astroglial cells are the provider of the d-serine that tonically activates the presynaptic NMDA receptor. We discuss the significance of these observations for the aetiology of epilepsy and possible targeting of the presynaptic NMDA receptor in anticonvulsant therapy. © 2014 Elsevier Ltd. All rights reserved

Twenty-first century glacier slowdown driven by mass loss in High Mountain Asia

International audienc