Spline-based cardiac motion tracking using velocity-encoded magnetic resonance imaging

This paper deals with the problem of tracking cardiac motion and deformation using velocity-encoded magnetic resonance imaging. We expand upon an earlier described method and fit a spatiotemporal motion model to measured velocity data. We investigate several different spatial elements both qualitatively and quantitatively using phantom measurements and data from human subjects. In addition, we also use optical flow estimation by the Horn–Schunk method as complementary data in regions where the velocity measurements are noisy. Our results show that it is possible to obtain good motion tracking accuracy in phantoms with relatively few spatial elements, if the type of element is properly chosen. The use of optical flow can correct some measurement artifacts but may give an underestimation of the magnitude of the deformation. In human subjects the different spatial elements perform quantitatively in a similar way but qualitative differences exists, as shown by a semiquantitative visual scoring of the different methods.      

Purification and characterisation of relevant natural and recombinant apple allergens

Apple (Malus domestica) is the most widely cultivated fruit crop in Europe and frequently causes allergic reactions with a variable degree of severity. So far, four apple allergens Mal d 1, Mal d 2, Mal d 3 and Mal d 4 have been identified. Mal d 1, a Bet v 1 related allergen, and Mal d 4, apple profilin, are sensitive to proteolytic degradation, whereas Mal d 2, a thaumatin-like protein and Mal d 3, a nonspecific lipid transfer protein, are rather stable to proteolytic processes. Mal d 1 and Mal d 4 were purified after expression in Escherichia coli expression system, while Mal d 2 and Mal d 3 were purified from apple fruit tissue. All purified proteins were subjected to detailed physicochemical characterisation to confirm their structural integrity and maintained IgE binding capacity. Detailed investigations of carbohydrate moieties of Mal d 2 demonstrated their involvement in the overall IgE binding capacity of this allergen. It was concluded that the folded structure and IgE binding capacity of all four allergens were preserved during purification.     

Electrolyte minerals intake and cardiovascular health

ABSTRACT

Appropriate intake of micronutrient, such as electrolyte minerals is critical for the well-being of the cardiovascular health system. However, there are some debates regarding the impacts of dietary and/or supplemental intake of these minerals, on the risk of cardiovascular events and associated risk factors. High sodium intake is adversely associated with the risk of hypertension. Although many reports refered to the positive association of Na intake and cardiovascular events and all-cause mortality, however, other studies indicated that low Na intake is related to higher risk of all-cause mortality and HF-related events. By contrast, dietary potassium, magnesium and calcium have an inverse correlation with cardiovascular events and risk factors, especially with blood pressure. There are some controversies about cardiovascular effects and all-cause mortality of high Ca intake, including no effect, preventive or adverse effect with or without vitamin D. Calcium supplementation might be beneficial for prevention of cardiovascular events and all-cause mortality only in individuals with low intake. Moreover, calcium intake showed a J- or U-shaped association with the risk of cardiovascular diseases. Due to the controversies of the effect of electrolyte minerals especially sodium and calcium intake on cardiovascular events, large scale, well-designed long-term randomized clinical trials are required to evaluate the effect of minerals intake on cardiovascular events and all-cause mortality. In this review, we discuss the role of dietary and or supplemental sodium, potassium, magnesium, calcium, in cardiovascular health, as well as their clinical applications, benefits, and risks for the primary prevention of cardiovascular disease, in general population.     

Furan and Methylfurans in Foods: An Update on Occurrence,Mitigation, and Risk Assessment

The acceptance of many foods is related to traditional cooking practices, which create taste and texture and are important to digestibility, preservation, and the reduction of foodborne illnesses. A wide range of compounds are formed during the cooking of foods, a number of these have been shown to lead to adverse effects in classical toxicological models and are known as food processing contaminants (FPC). It is essential that the presence and effects of such compounds alone and in combination within the diet are understood such that proportionate risk management measures can be developed, while taking a holistic view across the whole value chain. Furan and alkylfurans (principally 2‐ and 3‐methylfuran) are highly volatile FPC, which are formed in a wide range of foods at low amounts. The focus of research to‐date has been on those foods, which have been identified to be most consequential in terms of being sources of exposure, namely jarred and canned foods for infants and young children (meals and drinks) and coffee (roast and ground, soluble). This report presents (i) new industry data on the occurrence of furan and methylfurans in selected food categories following previous coffee studies, (ii) the most salient parameters that impact furan formation, and (iii) aspects of importance for the risk assessment.     

Targeted Synthesis of Complex Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-ones by Intramolecular Cyclization of Azomethine Ylides: Highly Potent MDM2–p53 Inhibitors

Mouse double minute 2 (MDM2) is a main and direct inhibitor of the crucial tumor suppressor p53. Reports from initial clinical trials showed that blocking this interaction with a small-molecule inhibitor can have great value in the treatment of cancer for patients with p53 wild-type tumors; however, it also revealed dose-limiting hematological toxicities and drug-induced resistance as main issues. To overcome the former, an inhibitor with superior potency and pharmacokinetic properties to ultimately achieve full efficacy with less-frequent dosing schedules is required. Toward this aim, we optimized our recently reported spiro-oxindole inhibitors by focusing on the crucial interaction with the amino acid side chain of His96_MDM2. The designed molecules required the targeted synthesis of structurally complex spiro[indole-3,2′-pyrrolo[2,3-c]pyrrole]-2,4′-diones for which we developed an unprecedented intramolecular azomethine ylide cycloaddition and investigated the results by computational methods. One of the new compounds showed superior cellular potency over previously reported BI-0252. This finding is a significant step toward an inhibitor suitable to potentially mitigate hematological on-target adverse effects.     

A New Lead Identification Strategy: Screening an sp3-rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives

Although the advantages of sp³-rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp²-rich components. Compounds that are sp³-rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp³-rich libraries. By modifying sp³-rich 7-azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp³-rich, but also had sufficient “lead-like” properties in view of molecular weights and hydrophobicity. Screening assays of this library provided weak κ opioid receptor agonists and growth hormone secretagogue receptor agonists with high hit rates. These results indicate that the 7-azanorbornane scaffold may be a “privileged structure” for lead identification in drug discovery.     

Investigation of bulk and solar cell properties of ingots cast from compensated solar grade silicon

In this work, the effect of the concurrent presence of B and P on bulk and solar cell properties of directionally solidified multicrystalline ingots from commercially compensated solar grade silicon (SoG‐Si) feedstock produced by Elkem Solar was investigated. The initial B and P content prior to the directional solidification experiment was 1260 and 762 ppba, respectively. Two reference ingots have been solidified in a silica crucible from 100% electronic grade silicon (EG‐Si) feedstock, with 332 ppba of boron added. All ingots have been cast under similar process parameters. The resistivity measurements by Four Point Probe (FPP) are in good agreement with the net dopant content, i.e., N_A − N_D for p‐type material, measured by Glow Discharge Mass Spectrometer (GDMS). Bulk lifetime measurements show a decrease in the values compared to the EG reference. Lifetime distributions show the highest values of 13 and 19 µs at approximately half ingot height, compared to 30 and 44 µs in the reference ingots. This decrease can be due to the concurrent effect of compensation and of other impurities present in the ingot. However, the content of several transition metals measured by GDMS at half ingot height was not significantly higher than that of the reference ingots. Oxygen content as measured by Fourier Transform Infra‐Red (FTIR) spectroscopy shows no significant difference compared to the references. Solar cells made from the compensated ingots and processed under standard process conditions show efficiency values up to 15.5% and fill factor values up to 78%, comparable to conventional multicrystalline silicon cells. Copyright © 2010 John Wiley & Sons, Ltd.     

Performance comparison of AlGaAs,GaAs and InGaP tunnel junctions for concentrated multijunction solar cells

Four tunnel junction (TJ) designs for multijunction (MJ) solar cells under high concentration are studied to determine the peak tunnelling current and resistance change as a function of the doping concentration. These four TJ designs are: AlGaAs/AlGaAs, GaAs/GaAs, AlGaAs/InGaP and AlGaAs/GaAs. Time‐dependent and time‐average methods are used to experimentally characterize the entire current–voltage profile of TJ mesa structures. Experimentally calibrated numerical models are used to determine the minimum doping concentration required for each TJ design to operate within a MJ solar cell up to 2000‐suns concentration. The AlGaAs/GaAs TJ design is found to require the least doping concentration to reach a resistance of <10⁻⁴ Ω cm² followed by the GaAs/GaAs TJ and finally the AlGaAs/AlGaAs TJ. The AlGaAs/InGaP TJ is only able to obtain resistances of ≥5 × 10⁻⁴ Ω cm² within the range of doping concentrations studied. Copyright © 2010 John Wiley & Sons, Ltd.     

Arrangement and fine structure of collagen fibrils in the decidualized mouse endometrium

The adaptations of the mouse uterus to pregnancy include extensive modifications of the cells and extracellular matrix of the endometrial connective tissue that surround the embryos. Around each implanted embryo this tissue redifferentiates into a transient structure called decidua, which is formed by polygonal cells joined by intercellular junctions. In the mouse, thick collagen fibrils with irregular profile appear in decidualized areas of the endometrium but not in the nondecidualized stroma and interimplantation sites. The fine organization of these thick fibrils has not yet been established. This work was addressed to understand the arrangement and fine structure of collagen fibrils of the decidua of pregnant mice during the periimplantation stage. Major modifications occurred in collagen fibrils that surrounded decidual cells: (1) the fibrils, which were arranged in parallel bundles in nonpregnant animals, became organized as baskets around decidual cells; (2) very thick collagen fibrils with very irregular profiles appeared around decidual cells. Analysis of replicas and serial sections suggests that the thick collagen fibrils form by the lateral aggregation of thinner fibrils to a central fibril resulting in very irregular profile observed in cross sections of thick fibrils. The sum of modifications of the collagen fibrils seem to represent an adaptation of the endometrium to better support the decidual cells while they hold the embryos during the beginning of their development. The deposition of thick collagen fibrils in the decidua may contribute to form a barrier that impedes leukocyte migration within the decidua, preventing immunological rejection of genetically dissimilar embryonic tissues.