Progress in high field MRI at the University of Florida

In this article we report on progress in high magnetic field MRI at the University of Florida in support of our new 750MHz wide bore and 11.7T/40cm MR instruments. The primary emphasis is on the associated rf technology required, particularly high frequency volume and phased array coils. Preliminary imaging results at 750MHz are presented. Our results imply that the pursuit of even higher fields seems warranted. (C) 2002 Elsevier Science B.V. All rights reserved.

Magnetic susceptibility of the normal-superconducting transition in high-purity single-crystal α-uranium

We report complex ac magnetic susceptibility measurements of a superconducting transition in very high-quality single-crystal alpha-uranium using microfabricated coplanar magnetometers. We identify an onset of superconductivity at Tapproximate to0.7 K in both the real and imaginary components of the susceptibility which is confirmed by resistivity data. A superconducting volume fraction argument, based on a comparison with a calibration YBa2Cu3O7-delta sample, indicates that superconductivity in these samples may be filamentary. Our data also demonstrate the sensitivity of the coplanar micro-magnetometers, which are ideally suited to measurements in pulsed magnetic fields exceeding 100 T.

A role for protein kinase B beta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes

Insulin stimulates glucose uptake into muscle and fat cells by promoting the translocation of glucose transporter 4 (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3K) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt, a downstream target of PI3K in regulation of GLUT4 translocation, has been controversial. Here we report that microinjection of a PKB substrate peptide or an antibody to PKB inhibited insulin-stimulated GLUT4 translocation to the plasma membrane by 66 or 56%, respectively. We further examined the activation of PKB isoforms following treatment of cells with insulin or platelet-derived growth factor (PDGF) and found that PKB beta is preferentially expressed in both rat and 3T3-L1 adipocytes, whereas PKB alpha expression is down-regulated in 3T3-L1 adipocytes. A switch in growth factor response was also observed when 3T3-L1 fibroblasts were differentiated into adipocytes. While PDGF was more efficacious than insulin in stimulating PKB phosphorylation in fibroblasts, PDGF did not stimulate PKB beta phosphorylation to any significant extent in adipocytes, as assessed by several methods. Moreover, insulin, but not PDGF, stimulated the translocation of PKB beta to the plasma membrane and high-density microsome fractions of 3T3-L1 adipocytes. These results support a role for PKB beta in insulin-stimulated glucose transport in adipocytes.

Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer

Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatellite instability (MSI-H) has a favorable prognosis. The reason for this MSI-H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody in a selected series of 100 sporadic colorectal cancers classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MISS). The Ki-67 index was significantly higher in MSI-H cancers (P < 0.0001) in which the PI was 90.1 1.2% (mean +/- SE) compared with 69.5 +/- 3.1 % and 69.5 +/- 2.3 % in MSI-L and MSS subgroups, respectively. There was a positive linear correlation between the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cancers demonstrating an increased AI:PI ratio indicative of a lower index of cell production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or MSS cancers. The Al was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers are characterized by a higher AL:PI ratio and increased proliferative activity compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.

Novel miniaturized systems in high-throughput screening

High-throughput screening (HTS) using high-density microplates is the primary method for the discovery of novel lead candidate molecules. However, new strategies that eschew 2D microplate technology, including technologies that enable mass screening of targets against large combinatorial libraries, have the potential to greatly increase throughput and decrease unit cost. This review presents an overview of state-of-the-art microplate-based HTS technology and includes a discussion of emerging miniaturized systems for HTS. We focus on new methods of encoding combinatorial libraries that promise throughputs of as many as 100 000 compounds per second.

Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four Pacific Island countries

The prevalence rate of hepatitis B virus (HBV) infection in Pacific Island countries is amongst the highest in the world. Hepatitis B immunisation has been incorporated into national programmes at various times, often with erratic supply and coverage, until a regionally co-ordinated programme, which commenced in 1995 ensured adequate supply. The effectiveness of these programmes was recently evaluated in four countries, Vanuatu and Fiji in Melanesia, Tonga in Polynesia and Kiribati in Micronesia. That evaluation established that the programmes had a substantial beneficial impact in preventing chronic hepatitis B infection [Vaccine 18 (2000) 3059]. Several studies of hepatitis B vaccination programmes in endemic countries have identified the potential significance of surface gene mutants as a cause for failure of immunisation. In the study outlined in this paper, we screened infected children and their mothers for the emergence and prevalence of these variants in specimens collected from the four country evaluation. Although the opportunity for the emergence of HBV vaccine escape mutants in these populations was high due to the presence of a considerable amount of the virus in the population and the selection pressure from vaccine use, there were no a determinant vaccine escape mutants found. This suggests that vaccine escape variants are not an important cause for failure to prevent HBV transmission in this setting. Other HBsAg variants were detected, but their functional significance remains to be determined. The failure to provide satisfactory protection during such immunisation programmes reflects the need for achieving and sustaining high vaccine coverage, improving the timeliness of doses as well as improving 'cold-chain' support, rather than the selection of vaccine-escape mutants of HBV. (C) 2004 Elsevier Ltd. All rights reserved.

A theoretical comparison of two optimization methods for radiofrequency drive schemes in high frequency MRI resonators

In this paper, numerical simulations are used in an attempt to find optimal Source profiles for high frequency radiofrequency (RF) volume coils. Biologically loaded, shielded/unshielded circular and elliptical birdcage coils operating at 170 MHz, 300 MHz and 470 MHz are modelled using the FDTD method for both 2D and 3D cases. Taking advantage of the fact that some aspects of the electromagnetic system are linear, two approaches have been proposed for the determination of the drives for individual elements in the RF resonator. The first method is an iterative optimization technique with a kernel for the evaluation of RF fields inside an imaging plane of a human head model using pre-characterized sensitivity profiles of the individual rungs of a resonator; the second method is a regularization-based technique. In the second approach, a sensitivity matrix is explicitly constructed and a regularization procedure is employed to solve the ill-posed problem. Test simulations show that both methods can improve the B-1-field homogeneity in both focused and non-focused scenarios. While the regularization-based method is more efficient, the first optimization method is more flexible as it can take into account other issues such as controlling SAR or reshaping the resonator structures. It is hoped that these schemes and their extensions will be useful for the determination of multi-element RF drives in a variety of applications.

Phase equilibria in high MgO ferro-manganese and silico-manganese smelting slags

Liquidus isotherms and phase equilibria have been determined experimentally for a pseudo-ternary section of the form MnO-(CaO+MgO)-(SiO2+Al2O3) with a fixed Al-2,O-3,/SiO2, weight ratio of 0.17 and MgO/CaO weight ratio of 0.17 for temperatures in the range 1473-1673 K. The primary phase fields present for the section investigated include manganosite (Mn,Mg,Ca)O; dicalcium silicate alpha-2(Ca,Mg,Mn)O (.) SiO2; merwinite 3CaO(.) ((Mg,Mn)O.2SiO(2); wollastonite [(Ca,Mg,Mn)(OSiO2)-Si-.]; ;tephroite [2(Mn,Mg)O.SiO2]; rhodonite [(Mn,Mg)O. diopside [(CaO,MgO,MnO,Al2O3)(SiO2)-Si-.]; tridymite (SiO2), SiO2] and melilite [2CaO (.) (MgO,MnO,Al2O3).2(SiO2,Al2O3)]. The liquidus temperatures relevant to ferro-manganese and silico-manganese smelting slags have been determined. The liquiclus temperature is shown to be principally dependent on the modified basicity weight ratio (CaO+Mgo)/(SiO2+Al2O3) at low MnO concentrations, and dependent on the mole ratio (CaO+ MgO+MnO)/(SiO2+Al2O3) at higher MnO concentrations.

Section thickness, macrohardness and yield strength in high-pressure diecast magnesium alloy AZ91

The yield strength of high-pressure diecast (hpdc) test bars of alloy AZ91 increases with decreasing section thickness while its hardness remains approximately constant. This behaviour is in contrast with that of the gravity cast alloy, whose hardness scales with the yield strength. Vickers hardness measured on the surface of hpdc test bars using increasing loads shows that the subsurface porosity layer usually found in hpdc material may gradually collapse under the indent, lowering the hardness. However, this is insufficient to explain the lack of correlation between hardness and yield strength. It is argued that the low strain-hardening rate of high-pressure diecast material leads to lower than expected hardness values. In addition, it is shown that the plastic zone under a macro indentation is largely contained by the softer core of the castings, rendering hardness insensitive to the casting thickness. It is concluded that macrohardness is too coarse a tool for a meaningful determination of the strength of hpdc material. (c) 2005 Elsevier B.V. All rights reserved.

Microhardness mapping and the hardness-yield strength relationship in high-pressure diecast magnesium alloy AZ91

Microhardness maps of cross-sections of high-pressure diecast test bars of AZ91 have been determined. Specimens with rectangular cross-sections, 1, 2 and 3 mm thick, or with a circular cross-section 6.4 mm in diameter, have been studied. The hardness is generally higher near the edges in all specimens, and more so near the corners of the rectangular specimens. The hardness at the center of the castings is generally lower, due to a coarser solidification microstructure and the concentration of porosity. The evidence confirms that the surface of the castings is harder than the core, but it does not support the concept of a skin with a sharp. and definable boundary. This harder layer is irregular in hardness and depth and is not equally hard on opposite sides of the casting. The mean hardness obtained by integrating the microhardness maps over the entire cross-section increased with decreasing thickness of the bars, and was found to be in good correlation with each bar's yield strength. (c) 2005 Elsevier B.V. All rights reserved.

Phase equilibria in high MgO ferro- and silico-manganese smelting slags

Phase equilibria have been determined experimentally for pseudo-ternary sections of the form “MnO”- (CaO+MgO)-(SiO2+Al2O3) with a fixed Al2O3/SiO2 weight ratio of 0.17 and MgO/CaO weight ratios of 0.25 and 0.17 respectively for temperatures in the range 1473-1673 K. The primary phase fields present for the MgO/CaO weight ratio of 0.17 include manganosite (Mn,Mg,Ca)O; dicalcium silicate α-2(Ca,Mg,Mn)O·SiO2; merwinite 3CaO⋅(Mg,Mn)O⋅2SiO2; wollastonite [(Ca,Mg,Mn)O·SiO2]; diopside [(CaO,MgO,MnO,Al2O3)·SiO2]; tridymite (SiO2); tephroite [2(Mn,Mg)O·SiO2]; rhodonite [(Mn,Mg)O·SiO2] and melilite [2CaO·(MgO,MnO,Al2O3)·2(SiO2,Al2O3)]. For the section with MgO/CaO weight ratio of 0.25 the anorthite phase (CaO⋅Al2O3⋅2SiO2) is also present. The liquidus temperatures of ferro- and silico-manganese smelting slags have been determined. The liquidus temperatures at low MnO concentrations are shown to be principally dependent on the modified basicity weight ratio (CaO+MgO)/(SiO2+Al2O3).