Design and simulation of a multi-function MEMS sensor for health and usage monitoring.

Health and usage monitoring as a technique for online test, diagnosis or prognosis of structures and systems has evolved as a key technology for future critical systems. The technology, often referred to as HUMS is usually based around sensors that must be more reliable than the system or structure they are monitoring. This paper proposes a fault tolerant sensor architecture and demonstrates the feasibility of realising this architecture through the design of a dual mode humidity/pressure MEMS sensor with an integrated temperature function. The sensor has a simple structure, good linearity and sensitivity, and the potential for implementation of built-in-self-test features. We also propose a re-configurable sensor network based on the multi-functional sensor concept that supports both normal operational and fail safe modes. The architecture has the potential to significantly increase system reliability and supports a reduction in the number of sensors required in future HUMS devices. The technique has potential in a wide range of applications, especially within wireless sensor networks

Directional Next-Generation RNA Sequencing and Examination of Premature Termination Codon Mutations in Endoglin/Hereditary Haemorrhagic Telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is a disease characterised by abnormal vascular structures, and most commonly caused by mutations in ENG, ACVRL1 or SMAD4 encoding endothelial cell-expressed proteins involved in TGF-β superfamily signalling. The majority of mutations reported on the HHT mutation database are predicted to lead to stop codons, either due to frameshifts or direct nonsense substitutions. The proportion is higher for ENG (67%) and SMAD4 (65%) than for ACVRL1 (42%), p < 0.0001. Here, by focussing on ENG, we report why conventional views of these mutations may need to be revised. Of the 111 stop codon-generating ENG mutations, on ExPASy translation, all except one were premature termination codons (PTCs), sited at least 50-55 bp upstream of the final exon-exon boundary of the main endoglin isoform, L-endoglin. This strongly suggests that the mutated RNA species will undergo nonsense-mediated decay. We provide new in vitro expression data to support dominant negative activity of stable truncated endoglin proteins but suggest these will not generate HHT: the single natural stop codon mutation in L-endoglin (sited within 50-55 nucleotides of the final exon-exon boundary) is unlikely to generate functional protein since it replaces the entire transmembrane domain, as would 8 further natural stop codon mutations, if the minor S-endoglin isoform were implicated in HHT pathogenesis. Finally, next-generation RNA sequencing data of 7 different RNA libraries from primary human endothelial cells demonstrate that multiple intronic regions of ENG are transcribed. The potential consequences of heterozygous deletions or duplications of such regions are discussed. These data support the haploinsufficiency model for HHT pathogenesis, explain why final exon mutations have not been detected to date in HHT, emphasise the potential need for functional examination of non-PTC-generating mutations, and lead to proposals for an alternate stratification system of mutational types for HHT genotype-phenotype correlations

Reading Motivation as a Moderator for Adolescent Literacy Outcomes

High school students often come to class without the necessary literacy proficiency for high school level content. English/Language Arts teachers find themselves needing to teach both grade level material alongside the basic, intermediate and disciplinary literacy skills students need to access text. Reading and writing proficiency for adolescent students in the United States is concerning in that the average student is reading and writing below grade level. In addition, adolescent students tend to lose reading motivation in middle and high school, yet motivation is linked to increased engagement and performance. This study examined the meaningful associations among the literacy components of spelling, vocabulary knowledge, reading performance and academic writing for adolescent students. Multiple regression analyses were used to explore if and how motivational constructs moderate established relationships between foundational literacy skills and knowledge (spelling and vocabulary) and broader literacy outcomes (reading performance and academic writing). The results showed that extrinsic motivation moderated two literacy relationships: vocabulary knowledge and reading performance, as well as spelling and academic writing, Implications for research, practice, and policy are explored to help teachers be intentional in how they use reading motivation in their classroom to help facilitate literacy development broadly. Key terms: literacy, high school, literacy stages, academic writing, readin

Musicology and Mediation: an examination of the cultural materialisms of Raymond Williams and Pierre Bourdieu in relation to the fields of contemporary music and musicology, with a case study of Arvo Part and ECM

Merged with duplicate record 10026.1/2795 on 06.20.2017 by CS (TIS)This thesis examines the usefulness of the work of Pierre Bourdieu and Raymond Williams for discussions of material mediation in musicology. In part I, I focus on Bourdieu's discussions of cultural production as set out in The Rules of Art and "The Field of Cultural Production", and reconstruct the terms of Williams's late theoretical project. In establishing the terms of these projects, I draw a parallel between their attempts to materialize the categories of Marx's superstructure - noting in Williams's subsequent use of a revised Marxist production paradigm a proximity to the work of Adorno - before noting the differences imposed by the pressures and limits of their respective intellectual cultures. The tensions between these two models are therefore identified as the opportunity for dialogue between theoretical traditions. In part 2, these reflections are tested through a discussion of Arvo Pärt's music and the record label Edition of Contemporary Music (ECM). Using data from musical scores, CDs, reviews, critical essays, magazine articles, interviews, and so on, Part's emergent field position in the late 1970s and early 1980s is reconstructed and ECM's function as both institution and artistic formation is argued. These instances of musical practice remain rhetorically committed to the ideals of autonomy while spanning the opposition of autonomy and heteronomy. This ambiguity puts strain on Williams's and Bourdieu's readings of cultural production, allowing for a critical approach to this range of debate. In this sense, the method becomes part of the subject matter, and the discussions combine both theoretical and musical reflection

Microbic dissociation in the acid-fast bacilli with special reference to the biological characters and virulence of the bacillus of calmette and guérin (B.C.G.)

1. Evidence of microbic dissociation as shown by variation in colonial form has been found. The types found were 'rough', 'smooth', and 'intermediate'. The great majority of colonies were of the ' intermediate' -type. The 'rough' type of colony corresponded closely with that described by Petroff, but the 'smooth' type did not.2. Evidence of microbic dissociation' was also found with two other acid -fast bacilli, namely the smegma bacillus, and one of Clegg's leprosy bacilli, 'rough' and 'smooth' colonies being found.3. Experiments on guinea -pigs have not shown clean cut lines of demarcation between the 'rough' and 'intermediate' types of colony, but definite variation was found, the 'smooth' type being most virulent, the 'rough' type second in virulence, and the 'intermediate' type the least virulent. Evidence of invasion of internal organs following subcutaneous injection was found in all types.Petroff, though finding the 'R' type relatively avirulent, found evidence of tuberculosis following intra-ventricular inoculation with 'R' type, two animals dying from this cause on the 266th and 375th days, and in one animal lesions were found in the spleen following intra-testicular injection with 'R' type.Be considers that these results may have been due to 'S' type organisms still remaining in the 'R' culture, and as there are considerable difficulties in separating them completely, this may be an explanation in my own experiments.4. On inoculating guinea-pigs with a subculture of B.C.G. on Dorset's egg-medium, results showed that the culture was more virulent than the 'intermediate' type of growth. This would seem to be explained by Petroff's finding that the 'S' type of organism did not grow on glycerol-bile-potato medium, but that it grew on ordinary media.Subcultures of B.C.G., therefore, on ordinary media would tend to grow more and more virulent.5. In the time at my disposal no guinea -pigs died following subcutaneous inoculation of any of the types of organism, although many showed active lesions¡ in internal organs which might have lead to a fatal issue had time permitted. Petroff, on the other hand, did have deaths following subcutaneous inoculation of the 'S' type, but on the 103rd day, a longer period than I allowed in my experiments.Another interesting point is that of forty-two guinea-pigs five died of ill -defined intercurrent diseases and these five were among the 21 which received intra-ventricular inoculations.Death occurred on the 18th day or later, and it is possible that these deaths were due to pathological conditions produced by the inoculations although not, apparently, tuberculosis.6. The types of lesion found were aggregations of lymphocytes and large mononuclear cells, but no giant cells were found. Occasionally necrosis, and in many cases fibrosis, was present

Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial

Background: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. Patients and methods: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m2 twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m2 with i.v. leucovorin 20 mg/m2 on days 1-5, repeated every 28 days (n = 974). Results: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or ≥65 years old. Conclusions: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in 2004. Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cance

Use of the viral 2A peptide for bicistronic expression in transgenic mice

Background: Transgenic animals are widely used in biomedical research and biotechnology. Multicistronic constructs, in which several proteins are encoded by a single messenger RNA, are commonly used in genetically engineered animals. This is currently done by using an internal ribosomal entry site to separate the different coding regions. 2A peptides result in the co-translational 'cleavage' of proteins and are an attractive alternative to the internal ribosomal entry site. They are more reliable than the internal ribosomal entry site and lead to expression of multiple cistrons at equimolar levels. They work in a wide variety of eukaryotic cells, but to date have not been demonstrated to function in transgenic mice in an inheritable manner. Results: To test 2A function in transgenic mice and uncover any possible toxicity of widespread expression of the 2A peptide, we made a bicistronic reporter construct containing the coding sequence for a membrane localised red fluorescent protein (Myr-TdTomato) and a nuclear localised green fluorescent protein (H2B-GFP), separated by a 2A sequence. When this reporter is transfected into HeLa cells, the two fluorescent proteins correctly localise to mutually exclusive cellular compartments, demonstrating that the bicistronic construct is a reliable readout of 2A function. The two fluorescent proteins also correctly localise when the reporter is electroporated into chick neural tube cells. We made two independent transgenic mouse lines that express the bicistronic reporter ubiquitously. For both lines, transgenic mice are born in Mendelian frequencies and are found to be healthy and fertile. Myr-TdTomato and H2B-GFP segregate to mutually exclusive cellular compartments in all tissues examined from a broad range of developmental stages, ranging from embryo to adult. One transgenic line shows X-linked inheritance of the transgene and mosaic expression in females but uniform expression in males, indicating that the transgene has integrated into the X chromosome in this line. Conclusion: The 2A peptide efficiently mediates co-translational cleavage in transgenic mice in which it has been inherited through the germ-line. Mice expressing it ubiquitously throughout development and into adulthood appear normal. It is therefore a viable tool for use in genetically engineered mice and represents a superior alternative to the widely used internal ribosomal entry site