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"Thomas, George"
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Neuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions
A major challenge in Parkinson’s disease is the variability in symptoms and rates of progression, underpinned by heterogeneity of pathological processes. Biomarkers are urgently needed for accurate diagnosis, patient stratification, monitoring disease progression and precise treatment. These were previously lacking, but recently, novel imaging and fluid biomarkers have been developed. Here, we consider new imaging approaches showing sensitivity to brain tissue composition, and examine novel fluid biomarkers showing specificity for pathological processes, including seed amplification assays and extracellular vesicles. We reflect on these biomarkers in the context of new biological staging systems, and on emerging techniques currently in development.
Biomarkers are needed in Parkinson’s for accurate diagnosis, to monitor progression and for targeted treatment. The authors reflect on recent imaging and fluid biomarkers for Parkinson’s and consider challenges in bringing them into clinical use.
Journal Article
The founders and the idea of a national university : constituting the American mind
\"This book examines the ideas of the Founders with regard to establishing a national university and what those ideas say about their understanding of America. It offers the first study on the idea of a national university and how the Founders understood it as an important feature in an educational system that would sustain the American experiment in democracy. Their ideas about education suggest that shaping the American mind is essential to the success of the Constitution and that this is something that future generations would need to continue to do\"-- Provided by publisher.
Book
UN ideas that changed the world
Ideas and concepts have been a driving force in human progress, and they
may be the most important legacy of the United Nations. UN ideas have set past,
present, and future international agendas in many global economic and social arenas
and have also led to initiatives and actions that have improved the quality of human
life. This capstone volume draws upon findings of the other 14 books in the
acclaimed United Nations Intellectual History Project Series. The authors not only
assess the development and implementation of UN ideas regarding sustainable economic
development and human security, but also apply lessons learned to suggest ways in
which the United Nations can play a fuller role in confronting the challenges of
human survival with dignity in the 21st century.
eBook
Self-healing ionic gelatin/glycerol hydrogels for strain sensing applications
Soft sensing technologies have the potential to revolutionize wearable devices, haptic interfaces and robotic systems. However, there are numerous challenges in the deployment of these devices due to their poor resilience, high energy consumption, and omnidirectional strain responsivity. This work reports the development of a versatile ionic gelatin-glycerol hydrogel for soft sensing applications. The resulting sensing device is inexpensive and easy to manufacture, is self-healable at room temperature, can undergo strains of up to 454%, presents stability over long periods of time, and is biocompatible and biodegradable. This material is ideal for strain sensing applications, with a linear correlation coefficient
R
2
= 0.9971 and a pressure-insensitive conduction mechanism. The experimental results show the applicability of ionic hydrogels for wearable devices and soft robotic technologies for strain, humidity, and temperature sensing while being able to partially self-heal at room temperature.
Versatile ionic gelatin-glycerol hydrogel for soft sensing applications: The sensing device is inexpensive and easy to manufacture, is self-healable at room temperature, can undergo strains of up to 454%, presents stability over long periods of time, and is biocompatible and biodegradable. This material is ideal for strain sensing applications, with a linear correlation coefficient R
2
= 0.9971 and a pressure-insensitive conduction mechanism. The experimental results show the applicability of ionic hydrogels for wearable devices and soft robotic technologies for strain, humidity and temperature sensing while being able to partially self-heal at room temperature.
Journal Article
Androgen receptor activity in T cells limits checkpoint blockade efficacy
Immune checkpoint blockade has revolutionized the field of oncology, inducing durable anti-tumour immunity in solid tumours. In patients with advanced prostate cancer, immunotherapy treatments have largely failed
1
–
5
. Androgen deprivation therapy is classically administered in these patients to inhibit tumour cell growth, and we postulated that this therapy also affects tumour-associated T cells. Here we demonstrate that androgen receptor (AR) blockade sensitizes tumour-bearing hosts to effective checkpoint blockade by directly enhancing CD8 T cell function. Inhibition of AR activity in CD8 T cells prevented T cell exhaustion and improved responsiveness to PD-1 targeted therapy via increased IFNγ expression. AR bound directly to
Ifng
and eviction of AR with a small molecule significantly increased cytokine production in CD8 T cells. Together, our findings establish that T cell intrinsic AR activity represses IFNγ expression and represents a novel mechanism of immunotherapy resistance.
. Androgen-receptor blockade can overcome immunotherapy resistance in prostate cancer by intrinsically enhancing T cell function and IFNγ responses.
Journal Article
Nanoparticles for the treatment of liver fibrosis
Chronic liver diseases represent a global health problem due to their high prevalence worldwide and the limited available curative treatment options. They can result from various causes, both infectious and noninfectious diseases. The application of nanoparticle (NP) systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for chronic liver diseases. This review presents the pathogenesis, diagnosis and the emerging nanoparticulate systems used in the treatment of chronic liver diseases caused by liver fibrosis. Activated hepatic stellate cell (HSC) is considered to be the main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A variety of nanoparticulate systems are mainly focused on targeting HSC in the treatment of hepatic fibrosis. As early liver fibrosis is reversible by current NP therapy, it is being studied in preclinical as well as clinical trials. Among various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their distinct properties to deliver drugs as well as other therapeutic moieties. Liposomal NPs in clinical trials is considered to be a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver fibrosis is updating fast, and hopefully, it can be the future remedy for liver fibrosis.
Journal Article