Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [¹¹¹In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.     

Sequence‐Defined Introduction of Hydrophobic Motifs and Effects in Lectin Binding of Precision Glycomacromolecules

This study investigates the influence of an increasingly hydrophobic backbone of multivalent glycomimetics based on sequence‐defined oligo(amidoamines) on their resulting affinity toward bacterial lectins. Glycomacromolecules are obtained by stepwise assembly of tailor‐made building blocks on solid support, using both hydrophobic aliphatic and aromatic building blocks to enable a gradual change in hydrophobicity of the backbone. Their binding behavior toward model lectin Concanavalin A (ConA) is evaluated using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) showing higher affinities for glycomacromolecules with higher content of hydrophobic and aromatic moieties in the backbone. Finally, glycomacromolecules are tested in a bacterial adhesion inhibition study against Escherichia coli where more hydrophobic backbones yield higher inhibitory potentials most likely due to additional secondary interactions with hydrophobic regions of the protein receptor as well as a change in conformation exposing carbohydrate ligands for increased binding. Overall, the results highlight the influence and thereby importance of the polymer backbone itself on the resulting properties of polymeric biomimetics.     

Controlling the Surface Functionalization of Ultrasmall Gold Nanoparticles by Sequence-Defined Macromolecules

Ultrasmall gold nanoparticles (diameter about 2 nm) were surface-functionalized with cysteine-carrying precision macromolecules. These consisted of sequence-defined oligo(amidoamine)s (OAAs) with either two or six cysteine molecules for binding to the gold surface and either with or without a PEG chain (3400 Da). They were characterized by ¹H NMR spectroscopy, ¹H NMR diffusion-ordered spectroscopy (DOSY), small-angle X-ray scattering (SAXS), and high-resolution transmission electron microscopy. The number of precision macromolecules per nanoparticle was determined after fluorescent labeling by UV spectroscopy and also by quantitative ¹H NMR spectroscopy. Each nanoparticle carried between 40 and 100 OAA ligands, depending on the number of cysteine units per OAA. The footprint of each ligand was about 0.074 nm² per cysteine molecule. OAAs are well suited to stabilize ultrasmall gold nanoparticles by selective surface conjugation and can be used to selectively cover their surface. The presence of the PEG chain considerably increased the hydrodynamic diameter of both dissolved macromolecules and macromolecule-conjugated gold nanoparticles.     

Escherichia coli single-stranded DNA-binding protein,a molecular tool for improved sequence quality in pyrosequencing

Pyrosequencing is a four-enzyme bioluminometric DNA sequencing technique based on a DNA sequencing by synthesis principle. Currently, the technique is limited to analysis of short DNA sequences exemplified by single-nucleotide polymorphism analysis. In order to expand the field for pyrosequencing, the read length needs to be improved and efforts have been made to purify reaction components as well as add single-stranded DNA-binding protein (SSB) to the pyrosequencing reaction. In this study, we have performed a systematic effort to analyze the effects of SSB by comparing the pyrosequencing result of 103 independent complementary DNA (cDNA) clones. More detailed information about the cause of low quality sequences on templates with different characteristics was achieved by thorough analysis of the pyrograms. Also, real-time biosensor analysis was performed on individual cDNA clones for investigation of primer annealing and SSB binding on these templates. Results from these studies indicate that templates with high performance in pyrosequencing without SSB possess efficient primer annealing and low SSB affinity. Alternative strategies to improve the performance in pyrosequencing by increasing the primer-annealing efficiency have also been evaluated.     

Perfect state transfer in Laplacian quantum walk

For a graph G and a related symmetric matrix M, the continuous-time quantum walk on G relative to M is defined as the unitary matrix \(U(t) = \exp (-itM)\), where t varies over the reals. Perfect state transfer occurs between vertices u and v at time \(\tau \) if the (u, v)-entry of \(U(\tau )\) has unit magnitude. This paper studies quantum walks relative to graph Laplacians. Some main observations include the following closure properties for perfect state transfer. If an n-vertex graph has perfect state transfer at time \(\tau \) relative to the Laplacian, then so does its complement if \(n\tau \in 2\pi {\mathbb {Z}}\). As a corollary, the join of \(\overline{K}_{2}\) with any m-vertex graph has perfect state transfer relative to the Laplacian if and only if \(m \equiv 2\pmod {4}\). This was previously known for the join of \(\overline{K}_{2}\) with a clique (Bose et al. in Int J Quant Inf 7:713–723, 2009). If a graph G has perfect state transfer at time \(\tau \) relative to the normalized Laplacian, then so does the weak product \(G \times H\) if for any normalized Laplacian eigenvalues \(\lambda \) of G and \(\mu \) of H, we have \(\mu (\lambda -1)\tau \in 2\pi {\mathbb {Z}}\). As a corollary, a weak product of \(P_{3}\) with an even clique or an odd cube has perfect state transfer relative to the normalized Laplacian. It was known earlier that a weak product of a circulant with odd integer eigenvalues and an even cube or a Cartesian power of \(P_{3}\) has perfect state transfer relative to the adjacency matrix. As for negative results, no path with four vertices or more has antipodal perfect state transfer relative to the normalized Laplacian. This almost matches the state of affairs under the adjacency matrix (Godsil in Discret Math 312(1):129–147, 2011).     

Competitive exclusion and coexistence in a Leslie–Gower competition model with Allee effects

The classical competitive exclusion principle states that two populations competing for a limited resource cannot coexist, one of the populations will drive the other to extinction. We prove in this work that when one population is subject to Allee effects, then for certain parameter regimes both competing populations may either coexist or one population may drive the other to extinction depending on initial conditions.     

Transient Analysis for State-Dependent Queues with Catastrophes

Abstract

Queueing systems with catastrophes and state-dependent arrival and service rates are considered. For two types of queueing systems namely, queues with discouraged arrivals and infinite server queue, explicit expressions for the transient probabilities of system size are obtained by using continued fractions technique. Some system performance measures and steady-state probabilities are studied. The effect of system parameters on system size probabilities are also illustrated numerically. It is observed that the steady-state probabilities differ when catastrophes are present, while they are identical in the absence of catastrophes.     

XHSTT: an XML archive for high school timetabling problems in different countries

We present the progress on the benchmarking project for high school timetabling that was introduced at PATAT 2008. In particular, we announce the High School Timetabling Archive XHSTT-2011 with 21 instances from 8 countries and an evaluator capable of checking the syntax of instances and evaluating the solutions.     

A discrete two-stage population model: continuous versus seasonal reproduction

A discrete two-stage model which describes the dynamics of a population where juveniles and adults compete for different resources is developed. A motivating example is the green tree frog (Hyla cinerea) where tadpoles and adult frogs feed on separate resources. First, continuous breeding is assumed and the asymptotic behavior of the resulting autonomous model is fully analyzed. It is shown that the unique interior equilibrium is globally asymptotically stable when the inherent net reproductive number is greater than one. However, when the inherent net reproductive number is less than one, the population becomes extinct. Then a seasonal breeding described by a periodic birth rate with period 2 is assumed. It is proved that for this nonautonomous model a period two solution is globally asymptotically stable when the inherent net reproductive number is greater than one and when the inherent net reproductive number is less than one the population becomes extinct. Finally, the advantage (in terms of maximizing the number of juveniles and adults in the population over a fixed time period) of having a seasonal breeding is studied by comparing the average of the juvenile and adult numbers of the periodic solution for the nonautonomous model to the equilibrium solution of the autonomous model. Our results indicate that for high birth rates the equilibrium of the autonomous model is higher than the average of the two cycle solution. Therefore, all other factors being equal, seasonal breeding appears to be deleterious to populations with high birth rates. However, for low birth rates seasonal breeding can be beneficial. It is also shown that for a range of birth rates the nonautnomous model is persistent while the solution to the autonomous model goes to extinction.     

Discrete vs. continuum-scale simulation of radiative transfer in semitransparent two-phase media

The mathematical formulation of the continuum approach to radiative transfer modeling in two-phase semi-transparent media is numerically validated by comparing radiative fluxes computed by (i) direct, discrete-scale and (ii) continuum-scale approaches. The analysis is based on geometrical optics. The discrete-scale approach uses the Monte Carlo ray-tracing applied directly to real 3D geometry measured by computed tomography. The continuum-scale approach is based on a set of continuum-scale radiative transfer equations and associated radiative properties, and employs the Monte Carlo ray-tracing for computations of radiative fluxes and for computations of the radiative properties. The model two-phase media are reticulate porous ceramics and a particle packed bed, each composed of semitransparent solid and fluid phases. The results obtained by the two approaches are in good agreement within the limits of statistical uncertainty. The continuum-scale approach leads to a reduction in computational time by approximately one order of magnitude, and is therefore suited to treat radiative transfer problems in two-phase media in a wide range of engineering applications.