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Site-directed differentiation of human adipose derived mesenchymal stem cells to nucleus pulposus cells using an injectable hydroxyl-functional diblock copolymer worm gel
No full textAdipose-derived mesenchymal stem cells (ASCs) have been identified for their promising therapeutic potential to regenerate and repopulate the degenerate intervertebral disk (IVD), which is a major cause of lower back pain. The optimal cell delivery system remains elusive but encapsulation of cells within scaffolds is likely to offer a decisive advantage over the delivery of cells in solution by ensuring successful retention within the tissue. Herein we evaluate the use of a fully synthetic, thermoresponsive poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymer worm gel that mimics the structure of hydrophilic glycosaminoglycans. The objective was to use this gel to direct differentiation of human ASCs towards a nucleus pulposus (NP) phenotype, with or without the addition of discogenic growth factors TGFB or GDF-6. Accordingly, human ASCs were incorporated into a cold, free-flowing aqueous dispersion of the diblock copolymer, gelation induced by warming to 37 ◦C and cell culture was conducted for 14 days with or without growth factors to assess the expression of characteristic NP markers compared to those produced when using collagen gels. The shear-thinning nature of the biocompatible worm gel enabled encapsulated human ASCs to be injected into the IVD using a 21G needle. Moreover, we find significantly higher gene expression levels of ACAN, SOX9, KRT8 and KR18 for ASCs encapsulated within worm gels compared to collagen scaffolds, regardless of the growth factors employed. In summary, such wholly synthetic worm gels offer considerable potential as an injectable cell delivery scaffold for the treatment of degenerate disk disease by promoting the transition of ASCs towards an NP phenotype
In Pursuit of an Effective Treatment: The Past, Present, and Future of Clinical Trials in Inclusion Body Myositis
No full textPurpose of review: No clinical trial in sporadic inclusion body myositis (IBM) thus far has shown a clear and sustained therapeutic effect. We review previous trial methodology, explore why results have not translated into clinical practice, and suggest improvements for future IBM trials.Recent findings: Early trials primarily assessed immunosuppressive medications, with no significant clinical responses observed. Many of these studies had methodological issues, including small participant numbers, non-specific diagnostic criteria, short treatment and/or assessment periods, and insensitive outcome measures. Most recent IBM trials have instead focused on non-immunosuppressive therapies, but there is mounting evidence supporting a primary autoimmune aetiology, including the discovery of immunosuppression-resistant clones of cytotoxic T-cells and anti-CN-1A autoantibodies which could potentially be used to stratify patients into different cohorts. The latest trials have had mixed results. For example, bimagrumab, a myostatin blocker, did not affect the six-minute timed walk distance, whereas sirolimus, a promotor of autophagy, did. Larger studies are planned to evaluate the efficacy of sirolimus and arimoclomol.Summary: Thus far, no treatment for IBM has demonstrated a definite therapeutic effect, and effective treatment options in clinical practice are lacking. Trial design and ineffective therapies are likely to have contributed to these failures. Identification of potential therapeutic targets should be followed by future studies using a stratified approach and sensitive and relevant outcome measures.<br/
Supervised Learning Algorithms to Extract Market Sentiment: An Application using Commercial Real Estate Market
No full textSentiment analysis has become a key area of research in economics and finance with methods evolving from traditional survey-based analysis to computational linguistic techniques. New developments in data handling and analysis have allowed extracting sentiment from vast amounts of written documents. However, these methods depend heavily on the existence of training and test data sets. The choice of training data is critical in such applications. We show a novel application from a unique market – commercial real estate. There are several unique attributes of the real estate market that makes such analysis critical for insightful market intelligence. In the absence of training data sets for the UK commercial real estate (CRE) market, we propose the use of Amazon book reviews for real estate related products. Our analysis has shown, that the use of more than 200,000 book reviews, can train different supervised learning algorithms, which in turn, can capture the sentiment and more importantly, it can help predict the direct commercial real estate market trends
SOX9 is required for kidney fibrosis and activates NAV3 to drive renal myofibroblast function
No full textRenal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis dependson the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarringand organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humansand required for experimentally induced kidney fibrosis in mice. From genome-wide analysis, we identified Neuronnavigator 3 (NAV3) as acting downstream of SOX9 in kidney fibrosis. NAV3 increased in abundance and colocalizedwith SOX9 after renal injury in mice, and both SOX9 and NAV3 were present in diseased human kidneys. In an in vitromodel of renal pericyte transdifferentiation into myofibroblasts, we demonstrated that NAV3 was required formultiple aspects of fibrogenesis, including actin polymerization linked to cell migration and sustained activation ofthe mechanosensitive transcription factor YAP1. In summary, our work identifies a SOX9-NAV3-YAP1 axis involvedin the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention
Towards a Postcolonial Critical Realism
No full textThis article proposes postcolonial critical realism (PCR) as an ontological framework that explains the structuring relationship between racialised, colonial discourses and the social world. Beginning with the case study of the global climate crisis, it considers how scholars and activists have made sense of the present crisis, and how their discourses reflect and reproduce the climate crisis at large. To theorise the relationship between racialised, power-laden discourses and material reality, it derives five tenets of PCR: first, colonial discourses underlie, and interact with, material structures; second, coloniality is global and made visible through differential events and experiences; third, subaltern lived experiences reveal the nature of reality at large; fourth, coloniality is power-laden, sticky, and often invisible; and finally, decolonisation must target all three domains of the social world and their interactions. The article concludes by considering how this framework might enrich anticolonial thought in the social sciences, as well as social movements
Separating the causes of listening difficulties in children
No full textAuditory processing disorder (APD), defined here as a deficit in the way sounds are analysed by the brain, has remained a controversial topic within audiology for decades. Some of the controversy concerns what it is called. More substantively, even its existence has been questioned. That view has likely emerged because there has not been sufficient rigor in determining when difficulty in understanding speech has been the consequence of some type of auditory processing deficit, versus when it is the consequence of a cognitive deficit or a language deficit. This paper suggests that the field use the term “listening difficulty” as an umbrella term to indicate a reported deficit in recognising sounds or understanding speech, one possible cause of which is an APD. Other possible causes are hearing deficits, cognitive deficits, and language deficits. This paper uses a plausible, and hopefully non-controversial, model of speech understanding that comprises auditory processing, speech processing, and language processing, all potentially affected by the degree of attention applied and the listener’s memory ability. In a fresh approach to the construction of test batteries, the stages of the model are linked to tests designed to assess either all or selected parts of the processes involved. For two of the stages, a listener’s performance is quantified as the additional signal-to-noise ratio that he or she needs to function equivalently to his or her age peers. Subtraction of the deficits revealed by each test enables the contributions of each processing stage to a listening deficit to be quantified. As a further novel contribution, the impact of memory and attention on each test score is quantitatively allowed for, by an amount that depends on each test’s dependence on memory and attention. Attention displayed during the test is estimated from the fluctuations in performance during the test.The paper concludes with a summary of the research that must be conducted before the structured tests can be used to quantify the extent to which different potential causes of listening difficulties are responsible for real-life difficulties in an individual child.<br/
Integrating Formal Verification and Assurance:An Inspection Rover Case Study
No full textThe complexity and flexibility of autonomous robotic systems necessitates a range of distinct verification tools. This presents new challenges not only for design verification but also for assurance approaches. Combining the distinct formal verification tools, while maintaining sufficient formal coherence to provide compelling assurance evidence is difficult, often being abandoned for less formal approaches. In this paper we demonstrate, through a case study, how a variety of distinct formal techniques can be brought together in order to develop a justifiable assurance case. We use the AdvoCATE assurance case tool to guide our analyses and to integrate the artifacts from the formal methods that we use, namely: fret, cocosim and Event-B. While we present our methodology as applied to a specific Inspection Rover case study, we believe that this combination provides benefits in maintaining coherent formal links across development and assurance processes for a wide range of autonomous robotic systems
Effect of Ag on cathodic activation and corrosion behaviour of Mg-Mn-Ag alloys
No full textThe effect of Ag on cathodic activation and corrosion behaviour of Mg-Mn-Ag alloys are investigated in the present work. During corrosion, Mg-Ag intermetallic phase undergoes dealloying to form porous Ag-rich remnant whereas Ag in the alloy matrix is dissolved to form Ag+ ions that subsequently redeposit on the alloy surface via displacement reaction with Mg to form Ag nanoparticles, which lead to significant cathodic activation. The cathodic activation is a self-catalysed process since enhanced cathodic activity promotes anodic dissolution which, consequently, results in further enhancement of cathodic activity. Thus, the corrosion rate of Mg-2Mn-4Ag alloy increases significantly with immersion time
Gender similarities in emotion perception tasks in a Latino population
No full textBasic emotions are universally recognized, although differences across cultures and between genders have been described. We report results in two emotion recognition tasks, in a sample of healthy adults from Chile. Methods: One hundred ninety-two volunteers (mean 31.58 years, s.d. 8.36; 106 women) completed the Emotional Recognition Task in which they were asked to identify a briefly displayed emotion, and the Emotional Intensity Morphing Task, in which they viewed faces with increasing or decreasing emotional intensity and indicated when they either detected or no longer detected the emotion. Results: All emotions were recognized at above chance levels. The only sex differences present showed men performed better at identifying anger (p = 0.0485), and responded more slowly to fear (p = 0.0057), than women Discussion: These findings are consistent with some, though not all, prior literature on emotion perception. Crucially, we report for the first time, data on emotional perception in a healthy adult Latino population, which contributes to emerging literature on cultural differences in affective processing
Bounds for an integral of the modified Bessel function of the first kind and expressions involving it
No full textSimple upper and lower bounds are obtained for the integral ∫x0e−γttνIν(t)dt , x>0 , ν>−12 , 0<γ<1 . Most of our bounds for this integral are tight as x→∞ . We apply one of our inequalities to bound some expressions involving this integral. Two of these expressions appear in Stein's method for variance-gamma approximation, and our bounds will allow for a technical advancement to be made to the method