How to Win in High-Volume Manufacturing of Flexible/Printed Electronics

High-volume production of electronics on flexible substrates has been "on the cusp of happening" for the last ten years; and yet the few products that have come onto the market in that time have not lived up to the early hype. So where is the real opportunity in this industry - is there any at all? As technologists and entrepreneurs, how can we separate the hype from the promise, and find the areas we can have the greatest impact? There are strong lessons to be learned from experiences in the semiconductor industry and early printed electronics products, such as membrane switches. A careful and critical look at the industry will show that there is significant growth happening right now in ways and areas that are not talked about, and plenty of opportunity to have a large impact on the world in the near term

Two 'transitions': the political economy of Joyce Banda's rise to power and the related role of civil society organisations in Malawi

This is an Accepted Manuscript of an article published by Taylor & Francis in Review of African Political Economy on 21/07/2014, available online: http://www.tandfonline.com/doi/abs/10.1080/03056244.2014.90194

Transcription Factor-Mediated Epigenetic Regulation in the Healthy Brain and Neurological Disease

Proper cellular development and function is a complex process established by elaborate gene expression networks. These networks are regulated by epigenetic processes, which alter chromatin states and coordinate the binding of transcription factors (TFs) to regulatory elements (REs), such as enhancers, across the genome to facilitate gene expression. It follows then that a major experimental effort is to profile and understand the binding patterns of TFs to REs in various cellular types and contexts. Critically however, current TF profiling techniques are limited in their abilities to profile TF occupancy in targeted cellular populations and temporal windows, hindering investigations into epigenetic control in complex, multicellular systems, such as the brain. This dissertation focuses on two related areas: firstly, the design of new tools for profiling TF genome occupancy in the mouse brain in specific cellular populations and time periods, and secondly, investigating TF-mediated mechanisms of disease pathogenesis in animal models. In Chapter 2, we describe the development of a novel, viral-mediated method, termed adeno-associated virus (AAV) calling cards, for profiling binding sites of TFs across the genome in the live mouse brain. The AAV calling cards approach allows unique access to TF occupancy information that is inaccessible with other existing techniques, including cell type specificity (through Cre-mediated conditional expression) and historical binding (through longitudinal occupancy recording). Then, in Chapters 3 and 4, we apply this new technique to mouse models to investigate epigenetic misregulation in disease. Previous studies have demonstrated that a large portion of genetic variation associated with cellular dysfunction or disease exists in TF-bound enhancers, demonstrating the criticality of proper TF binding in maintaining cellular homeostasis. However, whether these elements are misregulated more broadly in disease contexts is unclear. In Chapter 3, we apply AAV calling cards to a model of acute seizure and uncover aberrant epigenetic regulation which is predictive of phenotypic outcomes. Particularly important in this study is the ability of AAV calling cards to record and integrate historical TF binding information, allowing linkage of antecedent epigenetic events to eventual seizure outcomes. Here, we longitudinally recorded prodromal enhancer activity to identify loci which are predictive of seizure severity. Next, in Chapter 4, we investigate epigenetic regulation in animal models and postmortem tissues from individuals with amyotrophic lateral sclerosis (ALS). In this study, we focus on a subset of ALS caused by a large hexanucleotide (G4C2) repeat expansion in the gene chromosome 9 open reading frame 72 (C9orf72), which is the most common genetic cause of ALS (C9ALS). Utilizing AAV calling cards as well as other established epigenomic profiling techniques, we observe broad epigenetic misregulation both in C9ALS mouse models and human tissues at the transcriptional and translational levels. Importantly, the C9ALS mouse models used in this study do not develop motor neuron degeneration or ALS-like phenotypes and were profiled at an early age, suggesting that these changes occur early in the disease process and are likely driven by C9orf72-related pathologic species, such as dipeptide repeat proteins (DPRs). Finally, in Chapter 5 we investigate the characteristic properties of C9orf72-specfic pathologies, including DPRs, in human C9ALS. We probed size and abundance of DNA expansions and DPRs in blood, cerebrospinal fluid, and postmortem tissues from C9ALS and sporadic ALS (sALS) individuals and identified novel correlations of C9ALS patient pathologies with clinical and demographic data. Moving forward, these data will facilitate mechanistic studies and clinical trials aimed at reducing or altering C9ALS pathologies in the central nervous system (CNS). In summary, the body of work detailed here extends our knowledge of TFs in both the healthy and diseased central nervous system (CNS), providing new insights into the role of epigenetic regulation in disease pathogenesis. Further, the establishment of AAV calling cards as a widely applicable epigenomic tool will empower innovative new studies in a variety of tissue and model systems

Qualitative investigation of patients' experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK

OBJECTIVES: To explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor-delivered model. DESIGN: A qualitative investigation using one-to-one interviews before and after patients' appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS). SETTING: A glaucoma clinic based in a tertiary ophthalmic specialist hospital in London. PARTICIPANTS: 43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate. RESULTS: Trust in the patient-provider relationship emerged as a key theme in patients' acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment. CONCLUSIONS: This study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery

Bath induced coherence and the secular approximation

Finding efficient descriptions of how an environment affects a collection of discrete quantum systems would lead to new insights into many areas of modern physics. Markovian, or time-local, methods work well for individual systems, but for groups a question arises: does system-bath or inter-system coupling dominate the dissipative dynamics? The answer has profound consequences for the long-time quantum correlations within the system. We consider two bosonic modes coupled to a bath. By comparing an exact solution to different Markovian master equations, we find that a smooth crossover of the equations-of-motion between dominant inter-system and system-bath coupling exists - but requires a non-secular master equation. We predict a singular behaviour of the dynamics, and show that the ultimate failure of non-secular equations of motion is essentially a failure of the Markov approximation. Our findings justify the use of time-local theories throughout the crossover between system-bath dominated and inter-system-coupling dominated dynamics.PostprintPeer reviewe

Understanding the Logistics for the Distribution of Heme in Cells

[Image: see text] Heme is essential for the survival of virtually all living systems—from bacteria, fungi, and yeast, through plants to animals. No eukaryote has been identified that can survive without heme. There are thousands of different proteins that require heme in order to function properly, and these are responsible for processes such as oxygen transport, electron transfer, oxidative stress response, respiration, and catalysis. Further to this, in the past few years, heme has been shown to have an important regulatory role in cells, in processes such as transcription, regulation of the circadian clock, and the gating of ion channels. To act in a regulatory capacity, heme needs to move from its place of synthesis (in mitochondria) to other locations in cells. But while there is detailed information on how the heme lifecycle begins (heme synthesis), and how it ends (heme degradation), what happens in between is largely a mystery. Here we summarize recent information on the quantification of heme in cells, and we present a discussion of a mechanistic framework that could meet the logistical challenge of heme distribution

The JSpecView Project: an Open Source Java viewer and converter for JCAMP-DX, and XML spectral data files

The JSpecView Open Source project began with the intention of providing both a teaching and research tool for the display of JCAMP-DX spectra. The development of the Java source code commenced under license in 2001 and was released as Open Source in March 2006. The scope was then broadened to take advantage of the XML initiative in Chemistry and routines to read and write AnIML and CMLspect documents were added

TFE3 Translocation-Associated Renal Cell Carcinoma Presenting as Avascular Necrosis of the Femur in a 19-Year-Old Patient: Case Report and Review of the Literature

In the United States, renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90–95% of all neoplasms arising from the kidney. According to the National Cancer Institute, 58 240 new cases and 13 040 deaths from renal cancer will occur in 2010. RCC usually occurs in older adults between the ages of 50 and 70 and is rare in young adults and children. We describe a case of a TFE3 translocation-associated RCC in a 19-year-old patient presenting as avascular necrosis of the femur. Due to the rarity of this malignancy, we present this case including a review of the existing literature relative to diagnosis and treatment