The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs.

The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel

Optimization Formulations for the Design of Low Embodied Energy Structures Made from Reused Elements

The building sector is one of the major contributors to material resource consumption, greenhouse gas emission and waste production. Load-bearing systems have a particularly large environmental impact because of their material and energy intensive manufacturing process. This paper aims to address the reduction of building structures environmental impacts through reusing structural elements for multiple service lives. Reuse avoids sourcing raw materials and requires little energy for reprocessing. However, to design a new structure reusing elements available from a stock is a challenging problem of combinatorial nature. This is because the structural system layout is a result of the available elements’ mechanical and geometric properties. In this paper, structural optimization formulations are proposed to design truss systems from available stock elements. Minimization of weight, cut-off waste and embodied energy are the objective functions subject to ultimate and serviceability constraints. Case studies focusing on embodied energy minimization are presented for: (1) three roof systems with predefined geometry and topology; (2) a bridge structure whose topology is optimized using the ground structure approach; (3) a geometry optimization to better match the optimal topology from 2 and available stock element lengths. In order to benchmark the energy savings through reuse, the optimal layouts obtained with the proposed methods are compared to weight-optimized solutions made of new material. For these case studies, the methods proposed in this work enable reusing stock elements to design structures embodying up to 71% less energy and hence having a significantly lower environmental impact with respect to structures made of new material

Defining binding efficiency and specificity of auxins for SCF(TIR1/AFB)-Aux/IAA co-receptor complex formation.

Structure-activity profiles for the phytohormone auxin have been collected for over 70 years, and a number of synthetic auxins are used in agriculture. Auxin classification schemes and binding models followed from understanding auxin structures. However, all of the data came from whole plant bioassays, meaning the output was the integral of many different processes. The discovery of Transport Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin perception and the role of auxin as molecular glue in the assembly of co-receptor complexes has allowed the development of a definitive quantitative structure-activity relationship for TIR1 and AFB5. Factorial analysis of binding activities offered two uncorrelated factors associated with binding efficiency and binding selectivity. The six maximum-likelihood estimators of Efficiency are changes in the overlap matrixes, inferring that Efficiency is related to the volume of the electronic system. Using the subset of compounds that bound strongly, chemometric analyses based on quantum chemical calculations and similarity and self-similarity indices yielded three classes of Specificity that relate to differential binding. Specificity may not be defined by any one specific atom or position and is influenced by coulomb matrixes, suggesting that it is driven by electrostatic forces. These analyses give the first receptor-specific classification of auxins and indicate that AFB5 is the preferred site for a number of auxinic herbicides by allowing interactions with analogues having van der Waals surfaces larger than that of indole-3-acetic acid. The quality factors are also examined in terms of long-standing models for the mechanism of auxin binding

Studies on the Optimization of Efficient Selection and Focus Field Coil Configurations

Magnetic Particle Imaging is an imaging modality that detects the distribution of magnetic tracer material. By use of oscillating magnetic fields, a tracer signal can be generated in a defined field of view (FOV). In order to specify the region, where a signal can be detected, a selection field can be used that features a field free point (FFP). Due to technical and medical limitations, the FOV that can be covered by such an FFP is very limited. However, an enlargement of the FOV is possible by use of focus fields. Instead of using separate electromagnetic coils to generate the selection and the focus field, a combined coil assembly that generates both fields can be used. Such a coil configuration, combining the features of a classical Maxwell coil setup and a single-sided coil arrangement, allows for a very power efficient way to generate these magnetic fields. In this work, different studies are carried out to optimize such a combined coil assembly with respect to the electrical power loss.

Bivariate Lagrange interpolation at the node points of non-degenerate Lissajous curves

Motivated by an application in Magnetic Particle Imaging, we study bivariate Lagrange interpolation at the node points of Lissajous curves. The resulting theory is a generalization of the polynomial interpolation theory developed for a node set known as Padua points. With appropriately defined polynomial spaces, we will show that the node points of non-degenerate Lissajous curves allow unique interpolation and can be used for quadrature rules in the bivariate setting. An explicit formula for the Lagrange polynomials allows to compute the interpolating polynomial with a simple algorithmic scheme. Compared to the already established schemes of the Padua and Xu points, the numerical results for the proposed scheme show similar approximation errors and a similar growth of the Lebesgue constant

A survey on bivariate Lagrange interpolation on Lissajous nodes

This article is a survey on recent research on bivariate polynomial interpolation on the node points of Lissajous curves. The resulting theory is a generalization of the generating curve approach developed for Lagrange interpolation on the Padua points. After classifying the different types of Lissajous curves, we give a short overview on interpolation and quadrature rules defined on the node points of the Lissajous curves. Further, we summarize some convergence results and show how the interpolating polynomials can be computed efficiently. Finally, the developed theory is applied to a practical problem from a medical imaging modality called Magnetic Particle Imaging