Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H₂ results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the ¹H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan ¹H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.     

Computer Vision and Pattern Recognition 2020

International Journal of Computer Vision -     

Model validation and model structure determination

This paper gives a tutorial overview of basic approaches for model validation and model structure determination.Work partially supported by the Swedish Research Council for Engineering Sciences under contract 98-654.     

Higher Order Barycentric Coordinates

In recent years, a wide range of generalized barycentric coordinates has been suggested. However, all of them lack control over derivatives. We show how the notion of barycentric coordinates can be extended to specify derivatives at control points. This is also known as Hermite interpolation. We introduce a method to modify existing barycentric coordinates to higher order barycentric coordinates and demonstrate, using higher order mean value coordinates, that our method, although conceptually simple and easy to implement, can be used to give easy and intuitive control at interactive frame rates over local space deformations such as rotations.     

The effects of limbic lesions on locomotion and stereotypy elicited by dopamine agonists in the rat

The purpose of this experiment was to investigate the functional contributions of various limbic structures to locomotion and stereotypy induced by dopaminergic drugs. Female rats were randomly assigned to one of 5 groups (n = 10-14 rats/group) that received either a lesion of the hippocampus (colchicine + kainic acid), basolateral amygdala (quinolinic acid), frontal cortex (aspiration), nucleus accumbens (ibotenic acid), or served as unoperated controls. Beginning at least 2 weeks following surgery locomotion (measured as photocell beam breaks) elicited by D-amphetamine (0.0, 0.32, 1.0 and 3.2 mg/kg), SKF 82958 (0.0, 0.04, 0.08 and 0.16 mg/kg) or quinpirole (0.0, 0.25, 0.1 and 0.5 mg/kg) was determined. In agreement with previous results rats with hippocampal lesions were hyperactive in response to amphetamine. In comparison to these changes in drug-induced locomotion, lesions of the basolateral amygdala, and frontal cortex had only minor effects on drug-induced locomotion. Lesions of the nucleus accumbens produced consistent hyperactivity that was suppressed by doses of amphetamine or quinpirole that elicited behavioral stereotypy. These results provide evidence suggesting that, in comparison to other limbic structures that have substantial inputs to the nucleus accumbens, the hippocampus play a relatively prominent role in the modulation of drug-induced locomotion.     

Issues in nonlinear stochastic grey box identification

Grey box identification refers to the practice of identifying dynamical systems in model structures exploiting partial prior information. This contribution reviews a method for stochastic grey box identification and surveys experiences and lessons of applying it to a number of industrial processes. Issues to be addressed include advantages and costs of introducing stochastics into the model, the question of what contribution must be expected from the model designer as opposed to what can be formalized in computer algorithms, and an outlook on future plans to resolve present shortcomings.     

Retinal neurostimulator for a multifocal vision prosthesis.

A neurostimulator application-specific integrated circuit (ASIC) with scalable circuitry that can stimulate 14 channels, has been developed for an epi-retinal vision prosthesis. This ASIC was designed to allow seven identical units to be connected to control up to 98 channels, with the ability to stimulate 14 electrodes simultaneously. The neurostimulator forms part of a vision prosthesis, designed to restore vision to patients who have lost their sight due to retinal diseases such as retinitis pigmentosa and macular degeneration. For charge balance, the neurostimulator was designed to stimulate with current sources and sinks operating together, and with the ability to drive a hexagonal mosaic of electrodes to reduce the electrical crosstalk that occurs when multiple bipolar stimulation sites are active simultaneously. A hexagonal mosaic of electrodes surrounds each stimulation site and has been shown to effectively isolate each site, increasing the ability to inject localized independent charge into multiple regions simultaneously.     

Prostanoid biosynthesis by blood monocytes of children with hyperprostaglandin E syndrome

Hyperprostaglandin E syndrome (HPS), the prenatal variant of Bartter's syndrome, is characterized by a marked and selective stimulation of prostaglandin E (PGE2) synthesis. In the study group HPS patients showed increased urinary levels of PGE2, an index of renal, and of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid (PGE-M), an index of systemic PGE2 synthesis of 470% and of 570%, respectively. In addition, plasma concentration of PGE-M was also elevated 6.3-fold when compared with a control group. The urinary levels of other prostanoids were unaltered. During indomethacin treatment in both groups prostanoid excretion rates were suppressed to similar levels. To investigate the origin of stimulated prostanoid biosynthesis in HPS patients CD14+ monocytes were isolated from plasma samples, and the prostanoid synthesis was analyzed. The pattern and amounts of metabolites synthesized from endogenous arachidonic acid pools did not vary significantly between monocytes of the HPS and the control group. Thromboxane A2 (TXA2) was formed as the major prostanoid product. Using PGH2 as an exogenous substrate, again no difference in PGE2 biosynthesis was observed, indicating no difference in PGE-synthetic activity between both groups. Additionally, mRNA expression analysis of CD14+ monocytes via RT-PCR delineated the constitutive expression of cyclooxygenase-1, cyclooxygenase-2, and thromboxane synthase mRNA in cells from HPS patients and controls without statistical differences between these two groups. In conclusion, our data show that monocytes are not the source for the increased PGE2 biosynthesis in children with HPS, and a genetic defect in PGE synthesis can be excluded as the primary event in the pathogenesis in HPS.     

Efficient reconstruction from non-uniform point sets

We propose a method for non-uniform reconstruction of 3D scalar data. Typically, radial basis functions, trigonometric polynomials or shift-invariant functions are used in the functional approximation of 3D data. We adopt a variational approach for the reconstruction and rendering of 3D data. The principle idea is based on data fitting via thin-plate splines. An approximation by B-splines offers more compact support for fast reconstruction. We adopt this method for large datasets by introducing a block-based reconstruction approach. This makes the method practical for large datasets. Our reconstruction will be smooth across blocks. We give reconstruction measurements as error estimations based on different parameter settings and also an insight on the computational effort. We show that the block size used in reconstruction has a negligible effect on the reconstruction error. Finally we show rendering results to emphasize the quality of this 3D reconstruction technique.