A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.

A wave equation technique for designing compact gradient coils

A primary purpose of this research is to design a gradient coil that is planar in construction and can be inserted within existing infrastructure. The proposed wave equation method for the design of gradient coils is novel within the field. it is comprehensively shown how this method can be used to design the planar x-, y-, and z-gradient wire windings to produce the required magnetic fields within a certain domain. The solution for the cylindrical gradient coil set is also elucidated. The wave equation technique is compared with the well-known target held method to gauge the quality of resultant design. In the case of the planar gradient coil design, it is shown that using the new method, a set of compact gradient coils with large field of view can be produced. The final design is considerably smaller in dimension when compared with the design obtained using the target field method, and therefore the manufacturing costs and materials required are somewhat reduced.

Convergence analysis of a discrete-time single-unit gradient ICA algorithm

We revisit the one-unit gradient ICA algorithm derived from the kurtosis function. By carefully studying properties of the stationary points of the discrete-time one-unit gradient ICA algorithm, with suitable condition on the learning rate, convergence can be proved. The condition on the learning rate helps alleviate the guesswork that accompanies the problem of choosing suitable learning rate in practical computation. These results may be useful to extract independent source signals on-line.

Sugarcane ShSUT1: analysis of sucrose transport activity and inhibition by sucralose

Plant sucrose transporters (SUTs) are members of the glycoside-pentoside-hexuronide (GPH) cation symporter family (TC2.A.2) that is part of the major facilitator superfamily (MFS). All plant SUTs characterized to date function as proton-coupled symporters and catalyze the cellular uptake of sucrose. SUTs are involved in loading sucrose into the phloem and sink tissues, such as seeds, roots and flowers. Because monocots are agriculturally important, SUTs from cereals have been the focus of recent research. Here we present a functional analysis of the SUT ShSUT1 from sugarcane, an important crop species grown for its ability to accumulate high amounts of sucrose in the stem. ShSUT1 was previously shown to be expressed in maturing stems and plays an important role in the accumulation of sucrose in this tissue. Using two-electrode voltage clamping in Xenopus oocytes expressing ShSUT1, we found that ShSUT1 is highly selective for sucrose, but has a relatively low affinity for sucrose (K-0.5 = 8.26 mM at pH 5.6 and a membrane potential of -137 mV). We also found that the sucrose analog sucralose (4,1 ',6 '-trichloro-4,1 ',6 '-trideoxygalactosucrose) is a competitive inhibitor of ShSUT1 with an inhibition coefficient (K-i) of 16.5 mM. The presented data contribute to our understanding of sucrose transport in plants in general and in monocots in particular.

The five families of sucrose-phosphate synthase genes in Saccharum spp. are differentially expressed in leaves and stem

Sucrose-phosphate synthase (SPS) is a key enzyme in the pathway of sucrose synthesis. Five different gene families encoding SPS have been reported in the Poaceae [Castleden CK, Aoki N, Gillespie VJ, MacRae EA, Quick WP, Buchner P, Foyer CH, Furbank RT, Lunn JE (2004) Evolution and function of the sucrose-phosphate synthase gene families in wheat and othergrasses. PlantPhysiology 135, 1753-1764]. Expression of the five families in leaf and stem tissues of Saccharum spp. at different stages of development was determined by quantitative real-time PCR. The type B and C families of SPS genes were predominantly expressed in both immature and mature leaves, whereas the two subfamilies making up the type D family were expressed at similar levels in all tissues examined. In the type A family, expression was lowest in leaves and increased from the meristem region down to internode 7 of the stem.

The identification and characterisation of alleles of sucrose phosphate synthase gene family III in sugarcane

Little is known about the extent of allelic diversity of genes in the complex polyploid, sugarcane. Using sucrose phosphate synthase (SPS) Gene (SPS) Family III as an example, we have amplified and sequenced a 400 nt region from this gene from two sugarcane lines that are parents of a mapping population. Ten single nucleotide polymorphisms (SNPs) were identified within the 400 nt region of which seven were present in both lines. In the elite commercial cultivar Q165(A), 10 sequence haplotypes were identified, with four haplotypes recovered at 9% or greater frequency. Based on SNP presence, two clusters of haplotypes were observed. In IJ76-514, a Saccharum officinarum accession, 8 haplotypes were identified with 4 haplotypes recovered at 13% or greater frequency. Again, two clusters of haplotypes were observed. The results suggest that there may be two SPS Gene Family III genes per genome in sugarcane, each with different numbers of different alleles. This suggestion is supported by sequencing results in an elite parental sorghum line, 403463-2-1, in which 4 haplotypes, corresponding to two broad types, were also identified. Primers were designed to the sugarcane SNPs and screened over bulked DNA from high and low Sucrose-containing progeny from a cross between Q165(A) and IJ76-514. The SNP frequency did not vary in the two bulked DNA samples, suggesting that these SNPs from this SPS gene family are not associated with variation in sucrose content. Using an ecotilling approach, two of the SPS Gene Family III haplotypes were mapped to two different linkage groups in homology group 1 in Q165(A). Both haplotypes mapped near QTLs for increased sucrose content but were not themselves associated with any sugar-related trait.

Particle tracking in a salinity gradient: A method for measuring sinking rate of individual phytoplankton in the laboratory

This paper presents a new method to measure the sinking rates of individual phytoplankton “particles” (cells, chains, colonies, and aggregates) in the laboratory. Conventional particle tracking and high resolution video imaging were used to measure particle sinking rates and particle size. The stabilizing force of a very mild linear salinity gradient (1 ppt over 15 cm) prevented the formation of convection currents in the laboratory settling chamber. Whereas bulk settling methods such as SETCOL provide a single value of sinking rate for a population, this method allows the measurement of sinking rate and particle size for a large number of individual particles or phytoplankton within a population. The method has applications where sinking rates vary within a population, or where sinking rate-size relationships are important. Preliminary data from experiments with both laboratory and field samples of marine phytoplankton are presented here to illustrate the use of the technique, its applications, and limitations. Whereas this paper deals only with sinking phytoplankton, the method is equally valid for positively buoyant species, as well as nonbiological particles.

An equivalent distributed magnetic current based FDTD method for the calculation of e-fields induced by gradient coils in MRI

This paper evaluates a low-frequency FDTD method applied to the problem of induced E-fields/eddy currents in the human body resulting from the pulsed magnetic field gradients in MRI. In this algorithm, a distributed equivalent magnetic current (DEMC) is proposed as the electromagnetic source and is obtained by quasistatic calculation of the empty coil's vector potential or measurements therein. This technique circumvents the discretizing of complicated gradient coil geometries into a mesh of Yee cells, and thereby enables any type of gradient coil modeling or other complex low frequency sources. The proposed method has been verified against an example with an analytical solution. Results are presented showing the spatial distribution of gradient-induced electric fields in a multilayered spherical phantom model and a complete body model.

Comparative study of symmetric and asymmetric cylindrical MRI gradient Y-coils in terms of induced eddy currents

We have recently introduced the concept of whole-body asymmetric MRI systems [1]. In this theoretical study, we investigate the PNS characteristics of whole-body asymmetric gradient systems as compared to conventional symmetric systems. Recent experimental evidence [2] supports the hypothesis of transverse gradients being the largest contributor of PNS due to induced electric currents. Asymmetric head gradient coils have demonstrated benefits in the past [3]. The numerical results are based on an anatomically-accurate 2mm-human voxel-phantom NORMAN [4]. The results of this study can facilitate the optimization of whole-body asymmetric gradients in terms of patient comfort/safety (less PNS), while prospering the use of asymmetric MRI systems for in-vivo medical interventions.