Smooth rational surfaces of degree eleven and sectional genus eight in the projective fivespace

This thesis is a study of linearly normal smooth rational surfaces of degree eleven and sectional genus eight in the projective fivespace. Surfaces satisfying these numerical invariants are special, in the sense that the first cohomology group of the sheaf O(1) on such surfaces has positive dimension. Our main result is a proof of the existence of a family of surfaces satisfying the prescribed numerical invariants above. The construction is done via linear systems and we describe the configuration of points blown up in the projective plane to obtain this rational surface. A corollary of this result is that there exists a smooth rational surface with Hilbert polynomial $P(n)=11\binom{n}{2}+4n+1$. We also present a list, generated by the adjunction mapping, of linear systems whom are the only possibilities for other families of surfaces with the prescribed numerical invariants. A continuation of this thesis has later been published as the article “Smooth Rational Surfaces of d=11 and pi=8 in P5” in Math. Scand. 119 (2016), no. 2, pp 169-196

Persona Generation from Aggregated Social Media Data

We develop a methodology for persona generation using real time social media data for the distribution of products via online platforms. From a large social media account containing more than 30 million interactions from users from 181 countries engaging with more than 4,200 digital products produced by a global media corporation, we demonstrate that our methodology can first identify both distinct and impactful user segments and then create persona descriptions by automatically adding pertinent features, such as names, photos, and personal attributes. We validate our approach by implementing the methodology into an actual working system that leverages large scale online user data for generation of persona descriptions. We present the overall methodological approach, data analysis process, and system development. Findings show this method can develop believable personas representing real groups of people using real-time online user data. Results have implications for those distributing products via online platforms.We develop a methodology for persona generation using real time social media data for the distribution of products via online platforms. From a large social media account containing more than 30 million interactions from users from 181 countries engaging with more than 4,200 digital products produced by a global media corporation, we demonstrate that our methodology can first identify both distinct and impactful user segments and then create persona descriptions by automatically adding pertinent features, such as names, photos, and personal attributes. We validate our approach by implementing the methodology into an actual working system that leverages large scale online user data for generation of persona descriptions. We present the overall methodological approach, data analysis process, and system development. Findings show this method can develop believable personas representing real groups of people using real-time online user data. Results have implications for those distributing products via online platforms

MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury

Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Objectives: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Methods: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Results: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. Conclusion: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders

Alarmins in frozen shoulder: a molecular association between inflammation and pain

Background: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. Purpose: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects. Study Design: Controlled laboratory study. Methods: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients with unstable shoulders (control). The samples were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies against alarmin molecules including high-mobility group protein B1 (HMGB1), interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5. Immunoreactivities were rated in a blinded fashion from “none” to “strong.” Immunohistochemical distribution within the capsule was noted. Before surgery, patient-ranked pain frequency, severity, stiffness, and the range of passive shoulder motion were recorded and statistically analyzed. Results: Compared with control patients, patients with frozen shoulder had greater frequency and severity of self-reported pain (P = .02) and more restricted range of motion in all planes (P < .05). H&E-stained capsular tissue from frozen shoulder showed fibroblastic hypercellularity and increased subsynovial vascularity. Immunoreactivity of alarmins was significantly stronger in frozen shoulder capsules compared with control capsules (P < .05). Furthermore, the expression of the alarmin molecule HMGB1 significantly correlated (r > 0.9, P < .05) with the severity of patient-reported pain. Conclusion: This study demonstrates a potential role for key molecular danger signals in frozen shoulder and suggests an association between the expression of danger molecules and the pain experienced by patients