A discrete least squares collocation method for two-dimensional nonlinear time-dependent partial differential equations

In this paper, we develop regularized discrete least squares collocation and finite volume methods for solving two-dimensional nonlinear time-dependent partial differential equations on irregular domains. The solution is approximated using tensor product cubic spline basis functions defined on a background rectangular (interpolation) mesh, which leads to high spatial accuracy and straightforward implementation, and establishes a solid base for extending the computational framework to three-dimensional problems. A semi-implicit time-stepping method is employed to transform the nonlinear partial differential equation into a linear boundary value problem. A key finding of our study is that the newly proposed mesh-free finite volume method based on circular control volumes reduces to the collocation method as the radius limits to zero. Both methods produce a large constrained least-squares problem that must be solved at each time step in the advancement of the solution. We have found that regularization yields a relatively well-conditioned system that can be solved accurately using QR factorization. An extensive numerical investigation is performed to illustrate the effectiveness of the present methods, including the application of the new method to a coupled system of time-fractional partial differential equations having different fractional indices in different (irregularly shaped) regions of the solution domain

Folic Acid and the American Food Supply: A historical account of the FDA's creation of the current folic acid regulations

During the 1980s, scientific studies began to uncover a link between the B-vitamin folic acid and a reduction in the prevalence of neural tube defects, including spina bifida and anencephaly. When Congress passed the Nutrition Labeling and Education Act of 1990, it included a command that the FDA consider the link between folic acid and neural tube defects to determine whether the evidence was strong enough to permit food manufacturers of products containing folic acid to make a claim that their products may help prevent neural tube defects. Although the FDA initially rejected the use of such a claim, faced with mounting pressure from the scientific community and other government agencies, it reversed course and allowed manufacturers to make certain health claims regarding folic acid. It also required that certain products be fortified with folic acid, while banning its addition to other products. This paper details this process in an attempt to show its complexity and the very serious issues it presents. Since the process is largely complete, the paper also attempts to evaluate the process, as a whole, to determine what the FDA did well and what, if anything, the FDA should have done differently

Promoting Program Evaluation Fidelity When Data Collectors Lack Research Design and Implementation Expertise

Within Extension, certain personnel, facilitators, and volunteers expected to conduct research in the form of program evaluation may have little or no training in effective research design and practices. This circumstance can lead to difficulties in the implementation of evaluation procedures, particularly with regard to program evaluation fidelity. In addition, a lack of familiarity with effective program evaluation and research methods may limit an individual\u27s understanding of the importance of evaluation itself, as well as the importance of fidelity in conducting an evaluation. Effective planning of, training in, and monitoring of program evaluation procedures is essential for maintaining fidelity and ensuring accurate evaluation of program outcomes

A multi spin echo pulse sequence with optimized excitation pulses and a 3D cone readout for hyperpolarized 13 C imaging.

PURPOSE: Imaging tumor metabolism in vivo using hyperpolarized [1-13 C]pyruvate is a promising technique for detecting disease, monitoring disease progression, and assessing treatment response. However, the transient nature of the hyperpolarization and its depletion following excitation limits the available time for imaging. We describe here a single-shot multi spin echo sequence, which improves on previously reported sequences, with a shorter readout time, isotropic point spread function (PSF), and better signal-to-noise ratio. METHODS: The sequence uses numerically optimized spectrally selective excitation pulses set to the resonant frequencies of pyruvate and lactate and a hyperbolic secant adiabatic refocusing pulse, all applied in the absence of slice selection gradients. The excitation pulses were designed to be resistant to the effects of B0 and B1 field inhomogeneity. The gradient readout uses a 3D cone trajectory composed of 13 cones, all fully refocused and distributed among 7 spin echoes. The maximal gradient amplitude and slew rate were set to 4 G/cm and 20 G/cm/ms, respectively, to demonstrate the feasibility of clinical translation. RESULTS: The pulse sequence gave an isotropic PSF of 2.8 mm. The excitation profiles of the optimized pulses closely matched simulations and a 46.10 ± 0.04% gain in image SNR was observed compared to a conventional Shinnar-Le Roux excitation pulse. The sequence was demonstrated with dynamic imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate in vivo. CONCLUSION: The pulse sequence was capable of dynamic imaging of hyperpolarized 13 C labeled metabolites in vivo with relatively high spatial and temporal resolution and immunity to system imperfections

Increasing the sensitivity of hyperpolarized [15 N2 ]urea detection by serial transfer of polarization to spin-coupled protons.

PURPOSE: Hyperpolarized 15 N-labeled molecules have been proposed as imaging agents for investigating tissue perfusion and pH. However, the sensitivity of direct 15 N detection is limited by the isotope's low gyromagnetic ratio. Sensitivity can be increased by transferring 15 N hyperpolarization to spin-coupled protons provided that there is not significant polarization loss during transfer. However, complete polarization transfer would limit the temporal window for imaging to the order of the proton T1 (2-3 s). To exploit the long T1 offered by storing polarization in 15 N and the higher sensitivity of 1 H detection, we have developed a pulse sequence for partial polarization transfer. METHODS: A polarization transfer pulse sequence was modified to allow partial polarization transfer, as is required for dynamic measurements, and that can be implemented with inhomogeneous B1 fields, as is often the case in vivo. The sequence was demonstrated with dynamic spectroscopy and imaging measurements with [15 N2 ]urea. RESULTS: When compared to direct 15 N detection, the sequence increased the signal-to-noise ratio (SNR) by a factor of 1.72 ± 0.25, where both experiments depleted ~20% of the hyperpolarization (>10-fold when 100% of the hyperpolarization is used). Simulations with measured cross relaxation rates showed that this sequence gave up to a 50-fold increase in urea proton polarization when compared to spontaneous polarization transfer via cross relaxation. CONCLUSION: The sequence gave an SNR increase that was close to the theoretical limit and can give a significant SNR benefit when compared to direct 13 C detection of hyperpolarized [13 C]urea

The application of AEM to mapping the aquifer and groundwater characteristics of the La Grange groundwater area, WA

This report describes the interpretation of a large airborne electromagnetic data survey that was designed to aid characterisation of groundwater systems in the La Grange groundwater allocation area which lies south of Broome, Western Australia. Characterisation of these systems is critical to developing policy around water use in the region, especially for the development of agriculture. This report is the second of two reports and it is designed to refine surfaces which are used as inputs to groundwater models. The volume defined by these surfaces viz. the seawater intrusion in the west, the top of the Jarlemai siltstone and the top of the Broome sandstone describes the portion of the Broome sandstone aquifer that is able to store water that can be used for human purposes, agriculture and mining. With the identification of palaeochannels in the La Grange groundwater allocation area and an improved analysis of geological structure from AEM results, most objectives of the survey have been realised. Palaeochannels were identified in the north of the La Grange groundwater allocation area, around La Grange Bay, and also in the south. Also in the south, faults were identified. It is hypothesised that these faults permit groundwater movement between the Broome sandstone, which is the important aquifer in the La Grange groundwater allocation area, and the Wallal sandstone which is the important aquifer south of the allocation area. Objectives relating to delineation of freshwater zones, and of water quality were not addressed. Although the top of the seawater intrusion was mapped, as was the top of the Broome sandstone near the coast, because freshwater and the sandstone matrix have similar electrical resistivities, it is difficult to map freshwater specifically

Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.

2H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-2H2]malate, following injection of [2,3-2H2]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized 2H MR spectroscopy at 7 T. Malate production was also imaged in EL4 tumors using a fast 2H chemical shift imaging sequence. The malate/fumarate ratio increased from 0.016 ± 0.02 to 0.16 ± 0.14 in EL4 tumors 48 h after drug treatment (P = 0.0024, n = 3), and from 0.019 ± 0.03 to 0.25 ± 0.23 in MDA-MB-231 tumors (P = 0.0001, n = 5) and from 0.016 ± 0.04 to 0.28 ± 0.26 in Colo205 tumors (P = 0.0002, n = 5) 24 h after drug treatment. These increases were correlated with increased levels of cell death measured in excised tumor sections obtained immediately after imaging. 2H MR measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate provide a potentially less expensive and more sensitive method for detecting cell death in vivo than 13C MR measurements of hyperpolarized [1,4-13C2]fumarate metabolism, which have been used previously for this purpose.Cambridge European Scholarship from the Cambridge Trus

Parents, children and the porous boundaries of the sexual family in law and popular culture

This article focuses on a perceived ideological overlap between popular cultural and judicial treatments of sex and conjugality that contributes to a discursive construction of parenthood and parenting. The author perceives that in both legal and popular cultural texts, there is a sense in which notions of ‘natural’ childhood are discursively constituted as being put at risk by those who reproduce outside of dominant sexual norms, and that signs of normative sexuality (typically in the form of heterosexual coupling) may be treated as a sign of safety. These ideas are rooted in ancient associations between fertility, sexuality and femininity that can also be traced in the historical development of the English language. With the help of commentators such as Martha Fineman, the article situates parents and children within a discourse of family which prioritises conjugality, with consequences for the ways in which the internal and external boundaries of families are delineated

Probing Reactivity and Substrate Specificity of Both Subunits of the Dimeric \u3ci\u3eMycobacterium tuberculosis\u3c/i\u3e FabH Using alkyl-CoA Disulfide Inhibitors and acyl-CoA Substrates

The dimeric Mycobacterium tuberculosis FabH (mtFabH) catalyses a Claisen-type condensation between an acyl-CoA and malonyl-acyl carrier protein (ACP) to initiate the Type II fatty acid synthase cycle. To analyze the initial covalent acylation of mtFabH with acyl-CoA, we challenged it with mixture of C6-C20 acyl-CoAs and the ESI-MS analysis showed reaction at both subunits and a strict specificity for C12 acyl CoA. Crystallographic and ESI-MS studies of mtFabH with a decyl-CoA disulfide inhibitor revealed a decyl chain bound in acyl-binding channels of both subunits through disulfide linkage to the active site cysteine. These data provide the first unequivocal evidence that both subunits of mtFabH can react with substrates or inhibitor. The discrepancy between the observed C12 acyl-CoA substrate specificity in the initial acylation step and the higher catalytic efficiency of mtFabH for C18-C20 acyl-CoA substrates in the overall mtFabH catalyzed reaction suggests a role for M. tuberculosis ACP as a specificity determinant in this reaction

A neutron diffraction study and mode analysis of compounds of the system La_1−xSr_xFeO_3−xF_x (x=1, 0.8, 0.5, 0.2) and an investigation of their magnetic properties

AbstractWe report here a detailed study of the system La1−xSrxFeO3−xFx, by neutron powder diffraction- and magnetic-measurements. All the compounds are robust antiferromagnetics with ordering temperatures well above room temperature. Magnetic moments are shown to align parallel to the c-axis. FC-ZFC measurements indicate a small canting of the magnetic moments, resulting in a ferromagnetic component with a maximum for La0.5Sr0.5FeO2.5F0.5. We show that the system exhibits a composition-driven transition from a phase, for low fluorination levels (x≤0.5), with Pnma symmetry and the usual system of octahedral tiltings, to a phase with space group Imma for higher fluorine contents, where a correlated distortion of the oxygen octahedra plays a significant role. The consistency of the structural models, with respect to the expected continuity of the amplitudes of the different distortion modes and the invariance of their internal form, was monitored through the symmetry mode decomposition of the structures