High-resolution morphological and biochemical imaging of articular cartilage of the ankle joint at 3.0 T using a new dedicated phased array coil: in vivo reproducibility study

OBJECTIVE: The objective of this study was to evaluate the feasibility and reproducibility of high-resolution magnetic resonance imaging (MRI) and quantitative T2 mapping of the talocrural cartilage within a clinically applicable scan time using a new dedicated ankle coil and high-field MRI. MATERIALS AND METHODS: Ten healthy volunteers (mean age 32.4 years) underwent MRI of the ankle. As morphological sequences, proton density fat-suppressed turbo spin echo (PD-FS-TSE), as a reference, was compared with 3D true fast imaging with steady-state precession (TrueFISP). Furthermore, biochemical quantitative T2 imaging was prepared using a multi-echo spin-echo T2 approach. Data analysis was performed three times each by three different observers on sagittal slices, planned on the isotropic 3D-TrueFISP; as a morphological parameter, cartilage thickness was assessed and for T2 relaxation times, region-of-interest (ROI) evaluation was done. Reproducibility was determined as a coefficient of variation (CV) for each volunteer; averaged as root mean square (RMSA) given as a percentage; statistical evaluation was done using analysis of variance. RESULTS: Cartilage thickness of the talocrural joint showed significantly higher values for the 3D-TrueFISP (ranging from 1.07 to 1.14 mm) compared with the PD-FS-TSE (ranging from 0.74 to 0.99 mm); however, both morphological sequences showed comparable good results with RMSA of 7.1 to 8.5%. Regarding quantitative T2 mapping, measurements showed T2 relaxation times of about 54 ms with an excellent reproducibility (RMSA) ranging from 3.2 to 4.7%. CONCLUSION: In our study the assessment of cartilage thickness and T2 relaxation times could be performed with high reproducibility in a clinically realizable scan time, demonstrating new possibilities for further investigations into patient groups.

Fixed block configuration GDDs with block size 6 and (3, r)-regular graphs

Chapter 1 is used to introduce the basic tools and mechanics used within this thesis. Most of the definitions used in the thesis will be defined, and we provide a basic survey of topics in graph theory and design theory pertinent to the topics studied in this thesis. In Chapter 2, we are concerned with the study of fixed block configuration group divisible designs, GDD(n; m; k; λ1; λ2). We study those GDDs in which each block has configuration (s; t), that is, GDDs in which each block has exactly s points from one of the two groups and t points from the other. Chapter 2 begins with an overview of previous results and constructions for small group size and block sizes 3, 4 and 5. Chapter 2 is largely devoted to presenting constructions and results about GDDs with two groups and block size 6. We show the necessary conditions are sufficient for the existence of GDD(n, 2, 6; λ1, λ2) with fixed block configuration (3; 3). For configuration (1; 5), we give minimal or nearminimal index constructions for all group sizes n ≥ 5 except n = 10, 15, 160, or 190. For configuration (2, 4), we provide constructions for several families ofGDD(n, 2, 6; λ1, λ2)s. Chapter 3 addresses characterizing (3, r)-regular graphs. We begin with providing previous results on the well studied class of (2, r)-regular graphs and some results on the structure of large (t; r)-regular graphs. In Chapter 3, we completely characterize all (3, 1)-regular and (3, 2)-regular graphs, as well has sharpen existing bounds on the order of large (3, r)- regular graphs of a certain form for r ≥ 3. Finally, the appendix gives computational data resulting from Sage and C programs used to generate (3, 3)-regular graphs on less than 10 vertices.

Hamilton decompositions of 6-regular abelian Cayley graphs

In 1969, Lovasz asked whether every connected, vertex-transitive graph has a Hamilton path. This question has generated a considerable amount of interest, yet remains vastly open. To date, there exist no known connected, vertex-transitive graph that does not possess a Hamilton path. For the Cayley graphs, a subclass of vertex-transitive graphs, the following conjecture was made: Weak Lovász Conjecture: Every nontrivial, finite, connected Cayley graph is hamiltonian. The Chen-Quimpo Theorem proves that Cayley graphs on abelian groups flourish with Hamilton cycles, thus prompting Alspach to make the following conjecture: Alspach Conjecture: Every 2k-regular, connected Cayley graph on a finite abelian group has a Hamilton decomposition. Alspach’s conjecture is true for k = 1 and 2, but even the case k = 3 is still open. It is this case that this thesis addresses. Chapters 1–3 give introductory material and past work on the conjecture. Chapter 3 investigates the relationship between 6-regular Cayley graphs and associated quotient graphs. A proof of Alspach’s conjecture is given for the odd order case when k = 3. Chapter 4 provides a proof of the conjecture for even order graphs with 3-element connection sets that have an element generating a subgroup of index 2, and having a linear dependency among the other generators. Chapter 5 shows that if Γ = Cay(A, {s1, s2, s3}) is a connected, 6-regular, abelian Cayley graph of even order, and for some1 ≤ i ≤ 3, Δi = Cay(A/(si), {sj1 , sj2}) is 4-regular, and Δi ≄ Cay(ℤ3, {1, 1}), then Γ has a Hamilton decomposition. Alternatively stated, if Γ = Cay(A, S) is a connected, 6-regular, abelian Cayley graph of even order, then Γ has a Hamilton decomposition if S has no involutions, and for some s ∈ S, Cay(A/(s), S) is 4-regular, and of order at least 4. Finally, the Appendices give computational data resulting from C and MAGMA programs used to generate Hamilton decompositions of certain non-isomorphic Cayley graphs on low order abelian groups.

Experimental investigation of regular fluids and nanofluids during flow boiling in a single microchannel at different heat fluxes and mass fluxes

The dissipation of high heat flux from integrated circuit chips and the maintenance of acceptable junction temperatures in high powered electronics require advanced cooling technologies. One such technology is two-phase cooling in microchannels under confined flow boiling conditions. In macroscale flow boiling bubbles will nucleate on the channel walls, grow, and depart from the surface. In microscale flow boiling bubbles can fill the channel diameter before the liquid drag force has a chance to sweep them off the channel wall. As a confined bubble elongates in a microchannel, it traps thin liquid films between the heated wall and the vapor core that are subject to large temperature gradients. The thin films evaporate rapidly, sometimes faster than the incoming mass flux can replenish bulk fluid in the microchannel. When the local vapor pressure spike exceeds the inlet pressure, it forces the upstream interface to travel back into the inlet plenum and create flow boiling instabilities. Flow boiling instabilities reduce the temperature at which critical heat flux occurs and create channel dryout. Dryout causes high surface temperatures that can destroy the electronic circuits that use two-phase micro heat exchangers for cooling. Flow boiling instability is characterized by periodic oscillation of flow regimes which induce oscillations in fluid temperature, wall temperatures, pressure drop, and mass flux. When nanofluids are used in flow boiling, the nanoparticles become deposited on the heated surface and change its thermal conductivity, roughness, capillarity, wettability, and nucleation site density. It also affects heat transfer by changing bubble departure diameter, bubble departure frequency, and the evaporation of the micro and macrolayer beneath the growing bubbles. Flow boiling was investigated in this study using degassed, deionized water, and 0.001 vol% aluminum oxide nanofluids in a single rectangular brass microchannel with a hydraulic diameter of 229 µm for one inlet fluid temperature of 63°C and two constant flow rates of 0.41 ml/min and 0.82 ml/min. The power input was adjusted for two average surface temperatures of 103°C and 119°C at each flow rate. High speed images were taken periodically for water and nanofluid flow boiling after durations of 25, 75, and 125 minutes from the start of flow. The change in regime timing revealed the effect of nanoparticle suspension and deposition on the Onset of Nucelate Boiling (ONB) and the Onset of Bubble Elongation (OBE). Cycle duration and bubble frequencies are reported for different nanofluid flow boiling durations. The addition of nanoparticles was found to stabilize bubble nucleation and growth and limit the recession rate of the upstream and downstream interfaces, mitigating the spreading of dry spots and elongating the thin film regions to increase thin film evaporation.

Fabrication of a Large, Ordered, Three-Dimensional Nanocup Array

Metallic nanocups provide a unique method for redirecting scattered light by creating magnetic plasmon responses at optical frequencies. Despite considerable development of nanocup fabrication processes, simultaneously achieving accurate control over the placement, orientation, and geometry of nanocups has remained a significant challenge. Here we present a technique for fabricating large, periodically ordered arrays of uniformly oriented three-dimensional gold nanocups for manipulating light at subwavelength scales. Nanoimprint lithography, soft lithography, and shadow evaporation were used to fabricate nanocups onto the tips of polydimethylsiloxane nanopillars with precise control over the shapes and optical properties of asymmetric nanocups.

Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

Lag Camera: A Moving Multi-Camera Array for Scene-Acquisition

Many applications, such as telepresence, virtual reality, and interactive walkthroughs, require a three-dimensional(3D)model of real-world environments. Methods, such as lightfields, geometric reconstruction and computer vision use cameras to acquire visual samples of the environment and construct a model. Unfortunately, obtaining models of real-world locations is a challenging task. In particular, important environments are often actively in use, containing moving objects, such as people entering and leaving the scene. The methods previously listed have difficulty in capturing the color and structure of the environment while in the presence of moving and temporary occluders. We describe a class of cameras called lag cameras. The main concept is to generalize a camera to take samples over space and time. Such a camera, can easily and interactively detect moving objects while continuously moving through the environment. Moreover, since both the lag camera and occluder are moving, the scene behind the occluder is captured by the lag camera even from viewpoints where the occluder lies in between the lag camera and the hidden scene. We demonstrate an implementation of a lag camera, complete with analysis and captured environments.

Effect of regular physical training on age-associated alteration of body composition in men

Body composition changes with increasing age in men, in that lean body mass decreases whereas fat mass increases. Whether this altered body composition is related to decreasing physical activity or to the known age-associated decrease in growth hormone secretion is uncertain. To address this question, three groups of healthy men (n = 14 in each group), matched for weight, height and body mass index, were investigated using dual-energy X-ray absorptiometry, indirect calorimetry and estimate of daily growth hormone secretion [i.e. plasma insulin-like growth factor I (IGF-I-) levels]. Group 1 comprised young untrained subjects aged 31.0 +/- 2.1 years (mean +/- SEM) taking no regular physical exercise; group 2 consisted of old untrained men aged 68.6 +/- 1.2 years; and group 3 consisted of healthy old men aged 67.4 +/- 1.2 years undergoing regular physical training for more than 10 years with a training distance of at least 30 km per week. Subjects in group 3 had for the past three years taken part in the 'Grand Prix of Berne', a 16.5-km race run at a speed of 4.7 +/- 0.6 min km-1 (most recent race). Fat mass was more than 4 kg higher in old untrained men (P < 0.01, ANOVA) than in the other groups (young untrained men, 12.0 +/- 0.9 kg; old untrained men, 16.1 +/- 1.0 kg; old trained men, 11.0 +/- 0.8 kg), whereas body fat distribution (i.e. the ratio of upper to lower body fat mass) was similar between the three groups. The lean mass of old untrained men was more than 3.5 kg lower (P < 0.02, ANOVA) than in the other two groups (young untrained men, 56.4 +/- 1.0 kg; old untrained men, 52.4 +/- 1.0 kg; old trained men, 56.0 +/- 1.0 kg), mostly because of a loss of skeletal muscle mass in the arms and legs (young untrained men, 24.0 +/- 0.5 kg; old untrained men 20.8 +/- 0.5 kg; old trained men, 23.6 +/- 0.7 kg; P < 0.01, ANOVA). Resting metabolic rate per kilogram lean mass decreased with increasing age independently of physical activity (r = -0.42, P < 0.005). Fuel metabolism was determined by indirect calorimetry at rest. Protein oxidation was similar in the three groups. Old untrained men had higher (P < 0.001) carbohydrate oxidation (young untrained men, 13.2 +/- 1.0 kcal kg-1 lean mass; old untrained men, 15.2 +/- 1.3 kcal Kg-1; old trained men, 7.8 +/- 0.8 kcal kg-1), but lower (P < 0.05, ANOVA) fat oxidation (young untrained men, 10.1 +/- 1.2 kcal kg-1 lean mass; old untrained men, 6.5 +/- 1.0 kcal kg-1; old trained men, 13.7 +/- 1.0 kcal kg-1) than the other two groups. Mean plasma IGF-I level in old trained men was higher than in old untrained men (P < 0.05), but was still lower than that observed in young untrained men (P < 0.005) (young untrained men, 236 +/- 24 ng mL-1; old untrained men, 119 +/- 13 ng mL-1; old trained men, 166 +/- 14 ng mL-1). In summary, regular physical training in older men seems to prevent the changes in body composition and fuel metabolism normally associated with ageing. Whether regular physical training in formerly untrained old subjects would result in similar changes awaits further study.

Development of an array of ion-selective microelectrodes aimed for the monitoring of extracellular ionic activities

In this study, we present the development and the characterization of a generic platform for cell culture able to monitor extracellular ionic activities (K+, NH4+) for real-time monitoring of cell-based responses, such as necrosis, apoptosis, or differentiation. The platform for cell culture is equipped with an array of 16 silicon nitride micropipet-based ion-selective microelectrodes with a diameter of either 2 or 6 microm. This array is located at the bottom of a 200-microm-wide and 350-microm-deep microwell where the cells are cultured. The characterization of the ion-selective microelectrode arrays in different standard and physiological solutions is presented. Near-Nernstian slopes were obtained for potassium- (58.6 +/- 0.8 mV/pK, n = 15) and ammonium-selective microelectrodes (59.4 +/- 3.9 mV/pNH4, n = 13). The calibration curves were highly reproducible and showed an average drift of 4.4 +/- 2.3 mV/h (n = 10). Long-term behavior and response after immersion in physiological solutions are also presented. The lifetime of the sensors was found to be extremely long with a high recovery rate.

High-density electrode array for imaging in vitro electrophysiological activity

The development of a high-density active microelectrode array for in vitro electrophysiology is reported. Based on the Active Pixel Sensor (APS) concept, the array integrates 4096 gold microelectrodes (electrode separation 20 microm) on a surface of 2.5 mmx2.5 mm as well as a high-speed random addressing logic allowing the sequential selection of the measuring pixels. Following the electrical characterization in a phosphate solution, the functional evaluation has been carried out by recording the spontaneous electrical activity of neonatal rat cardiomyocytes. Signals with amplitudes from 130 microVp-p to 300 microVp-p could be recorded from different pixels. The results demonstrate the suitability of the APS concept for developing a new generation of high-resolution extracellular recording devices for in vitro electrophysiology.

Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. Results Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. Keywords: Epigenetics; Whole genome array analysis; Balkan endemic nephropathy