DEVELOPMENT OF A VERSATILE HIGH SPEED NANOMETER LEVEL SCANNING MULTI-PROBE MICROSCOPE

The motivation for development of a multi-probe scanning microscope, presented in this dissertation, is to provide a versatile measurement tool mainly targeted for biological studies, especially on the mechanical and structural properties of an intracellular system. This instrument provides a real-time, three-dimensional (3D) scanning capability. It is capable of operating on feedback from multiple probes, and has an interface for confocal photo-detection of fluorescence-based and single molecule imaging sensitivity. The instrument platform is called a Scanning Multi-Probe Microscope (SMPM) and enables 45 microm by 45 microm by 10 microm navigation of specimen with simultaneous optical and mechanical probing with each probe location being adjustable for collocation or for probing with known probe separations. The 3D positioning stage where the specimen locates was designed to have nanometer resolution and repeatability at 10 Hz scan speed with either open loop or closed loop operating modes. The fine motion of the stage is comprises three orthogonal flexures driven by piezoelectric actuators via a lever linkage. The flexures design is able to scan in larger range especially in z axis and serial connection of the stages helps to minimize the coupling between x, y and z axes. Closed-loop control was realized by the capacitance gauges attached to a rectangular block mounted to the underside of the fine stage upon which the specimen is mounted. The stage's performance was studied theoretically and verified by experimental test. In a step response test and using a simple proportional and integral (PI) controller, standard deviations of 1.9 nm 1.8 nm and 0.41 nm in the x, y and z axes were observed after settling times of 5 ms and 20 ms for the x and y axes. Scanning and imaging of biological specimen and artifact grating are presented to demonstrate the system operation. For faster, short range scanning, novel ultra-fast fiber scanning system was integrated into the xyz fine stage to achieve a super precision dual scanning system. The initial design enables nanometer positioning resolution and runs at 100 Hz scan speed. Both scanning systems are capable of characterization using dimensional metrology tools. Additionally, because the high-bandwidth, ultra-fast scanning system operates through a novel optical attenuating lever, it is physically separate from the longer range scanner and thereby does not introduce additional positioning noise. The dual scanner provides a fine scanning mechanism at relatively low speed and large imaging area using the xyz stage, and focus on a smaller area of interested in a high speed by the ultra-fast scanner easily. Such functionality is beneficial for researchers to study intracellular dynamic motion which requires high speed imaging. Finally, two high end displacement sensor systems, a knife edge sensor and fiber interferometer, were demonstrated as sensing solutions for potential feedback tools to boost the precision and resolution performance of the SMPM

Analytic functions and complex integration

This paper presents some basic theory of analytic function. The class of analytic functions is formed by the complex functions of a complex variable which possess a derivative wherever the function is defined. Beginning with the definition of the derivative, the necessary and sufficient conditions for a function to be analytic at a point are developed. In order to prove that the derivative of an analytic function is itself analytic, the line integrals are defined. The exact differential and its relation to line integrals are discussed. Then Cauchy's theorem is stated. Since the proof of Cauchy's theorem is so complicated and can be found in most texts on complex variable, it is skipped. Lastly Cauchy's integral formula is developed. The formula is an ideal tool for the study of local properties of analytic functions. Particularly it helps to show that an analytic function has derivatives of all orders, which are then analytic. With this result, the converse of Cauchy's theorem, known as Morera's theorem, can be proved. Last, the paper discusses Liouville's theorem concerning entire function

Monitoring sessile droplet evaporation on a micromechanical device.

A bulk acoustic mode micro-electro-mechanical dual resonator platform is utilised to study the evaporation of sub-microliter water droplets from the surface of the resonator. An analytical formulation for the observed frequency shift and the measure dependence of resonant frequency on the modes of evaporation which is consistent with the optically derived data. The resonators access only a thin layer of the liquid through shear contact and, hence, the response is not affected by the bulk mass of the droplet to first order. A relationship between the droplet contact area and the elapsed time was established for the evaporation process and is used to derive a value of the diffusion coefficient of water in air that is found to be in reasonable agreement with literature values. This work introduces a new tool for the electro-mechanical monitoring of droplet evaporation with relevance to applications such as biosensing in liquid samples of sub-microliter volumes.Funding from the Royal Society and the Cambridge Trusts is acknowledged.This is the accepted manuscript version. The final version is available from the RSC at http://pubs.rsc.org/en/content/articlelanding/2014/an/c4an01389a#!divAbstract

Beethoven's D Major Sonata for Cello and Piano, Op. 102 No. 2: an annotated performer's edition based on the suggestions of Bernard Greenhouse

Honorary Doctor of Music Bernard Greenhouse has earned a worldwide reputation as one of the leading cellists of our generation. As the founding cellist of the Beaux Arts Trio, he has garnered international acclaim for his supreme artistry; and as a teacher, he has exerted major influence on many of today's cellists. This dissertation documents Greenhouse's approach to music making in the context of his interpretation of Beethoven's Sonata in D major for Cello and Piano, Op. 102 No. 2. In a series of interviews by the undersigned, Greenhouse demonstrates ways to seize the sonata's dramatic impulses. He refers to his own studies with Pablo Casals when discussing his approach to interpretation. Among his many suggestions, he emphasizes the performer's role in "turning music into speech that can be understood." To this end, he provides techniques for clear enunciation and for creating dynamic inflections and rhythmic momentum in the music. This dissertation begins by surveying Greenhouse's contribution to cello playing and existing literature related to Beethoven's D-major sonata and Greenhouse. Then it documents Greenhouse's suggestions for the sonata in the form of commentaries and measure-by-measure annotations in a performer's edition of the score. More than a set of specific instructions for how to perform Beethoven's sonata, this dissertation seeks to describe an approach to string playing that can apply in a wide variety of musical contexts

A genetic algorithm for the vehicle routing problem with time windows

The objective of the vehicle routing problem (VRP) is to deliver a set of customers with known demands on minimum-cost vehicle routes originating and terminating at the same depot. A vehicle routing problem with time windows (VRPTW) requires the delivery be made within a speci¯c time frame given by the customers. Prins (2004) recently proposed a simple and e®ective genetic algorithm (GA) for VRP. In terms of average solution cost, it outperforms most published tabu search results. We implement this hybrid GA to handle VRPTW. Both the implementation and computational results will be discussed

Spatio-temporal expression patterns of Arabidopsis thaliana and Medicago truncatula defensin-like genes

Plant genomes contain several hundred defensin-like (DEFL) genes that encode short cysteine-rich proteins resembling defensins, which are well known antimicrobial polypeptides. Little is known about the expression patterns or functions of many DEFLs because most were discovered recently and hence are not well represented on standard microarrays. We designed a custom Affymetrix chip consisting of probe sets for 317 and 684 DEFLs from Arabidopsis thaliana and Medicago truncatula, respectively for cataloging DEFL expression in a variety of plant organs at different developmental stages and during symbiotic and pathogenic associations. The microarray analysis provided evidence for the transcription of 71% and 90% of the DEFLs identified in Arabidopsis and Medicago, respectively, including many of the recently annotated DEFL genes that previously lacked expression information. Both model plants contain a subset of DEFLs specifically expressed in seeds or fruits. A few DEFLs, including some plant defensins, were significantly up-regulated in Arabidopsis leaves inoculated with Alternaria brassicicola or Pseudomonas syringae pathogens. Among these, some were dependent on jasmonic acid signaling or were associated with specific types of immune responses. There were notable differences in DEFL gene expression patterns between Arabidopsis and Medicago, as the majority of Arabidopsis DEFLs were expressed in inflorescences, while only a few exhibited root-enhanced expression. By contrast, Medicago DEFLs were most prominently expressed in nitrogen-fixing root nodules. Thus, our data document salient differences in DEFL temporal and spatial expression between Arabidopsis and Medicago, suggesting distinct signaling routes and distinct roles for these proteins in the two plant species

Specific inhibition of cyclooxygenase-2 down-regulates NF-kappaB activation in gastric cancer cells by blocking its nuclear translocation

published_or_final_versio

Spatial heterogeneity of habitat suitability for Rift Valley fever occurrence in Tanzania: an ecological niche modelling approach

Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics

In Vivo Blood Glucose Quantification Using Raman Spectroscopy

We here propose a novel Raman spectroscopy method that permits the noninvasive measurement of blood glucose concentration. To reduce the effects of the strong background signals produced by surrounding tissue and to obtain the fingerprint Raman lines formed by blood analytes, a laser was focused on the blood in vessels in the skin. The Raman spectra were collected transcutaneously. Characteristic peaks of glucose (1125 cm(-1)) and hemoglobin (1549 cm(-1)) were observed. Hemoglobin concentration served as an internal standard, and the ratio of the peaks that appeared at 1125 cm(-1) and 1549 cm(-1) peaks was used to calculate the concentration of blood glucose. We studied three mouse subjects whose blood glucose levels became elevated over a period of 2 hours using a glucose test assay. During the test, 25 Raman spectra were collected transcutaneously and glucose reference values were provided by a blood glucose meter. Results clearly showed the relationship between Raman intensity and concentration. The release curves were approximately linear with a correlation coefficient of 0.91. This noninvasive methodology may be useful for the study of blood glucose in vivo

Self-rated health in middle-aged and elderly Chinese : distribution, determinants and associations with cardio-metabolic risk factors

Background: Self-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese. Methods: Survey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression. Results: Thirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance. Conclusion: Only one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health