Biochemical,Structural, and Genetic Characterization of Tridecaptin A1, an Antagonist of Campylobacter jejuni

Bacillus circulans NRRL B‐30644 (now Paenibacillus terrae) was previously reported to produce SRCAM 1580, a bacteriocin active against the food pathogen Campylobacter jejuni. We have been unable to isolate SRCAM 1580, and did not find any genetic determinants in the genome of this strain. We now report the reassignment of this activity to the lipopeptide tridecaptin A₁. Structural characterization of tridecaptin A₁ was achieved through NMR, MS/MS and GC‐MS studies. The structure was confirmed through the first chemical synthesis of tridecaptin A₁, which also revealed the stereochemistry of the lipid chain. The impact of this stereochemistry on antimicrobial activity was examined. The biosynthetic machinery responsible for tridecaptin production was identified through bioinformatic analyses. P. terrae NRRL B‐30644 also produces paenicidin B, a novel lantibiotic active against Gram‐positive bacteria. MS/MS analyses indicate that this lantibiotic is structurally similar to paenicidin A.     

Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells

Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1‐agonist and anticancer activities. These experiments led to the identification of 9‐epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9‐Epipolygodial was found to maintain potency against apoptosis‐resistant cancer cells as well as those displaying the multidrug‐resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal–Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.     

Creating a Protective Shell for Reactive MoSi2 Particles in High‐Temperature Ceramics

Alumina encapsulated molybdenum silicide (MoSi₂) intermetallic particles were synthesized using a simple precipitation method followed by calcining at temperatures of 800°C–1000°C, to prevent the premature oxidation of MoSi₂ at high temperatures. The shell composition and the influence of the calcining temperature on microcapsule integrity were investigated by means of X‐ray photoelectron spectroscopy, X‐ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The results demonstrate that the composition and the mechanical stability of the alumina shell can be tuned by the annealing temperature. After calcining at 800°C and 850°C the alumina shell remains intact. Calcining at higher temperature promotes the formation of mullite, which leads to cracking of the shell. However, when annealed at 1000°C for 24 h these cracks were filled with mullite and preserved the molybdenum silicide particles. Furthermore, the mechanical stability of the shell was improved by applying an intermediate calcining treatment at 450°C prior to the annealing process at 1000°C.     

Effect of the sulfide concentration on zinc bio-precipitation in a single stage sulfidogenic bioreactor at pH 5.5

Dissolved zinc is present in natural waters and process streams generated by the mining and metallurgical industry. These streams usually have a low pH. By using sulfate reducing bacteria, sulfide can be produced that precipitates with zinc as zinc sulfide (sphalerite), which can be easily separated from the wastewater and even reused as zinc concentrate. In this study, a sulfate reducing gas-lift bioreactor was operated at pH 5.5 using hydrogen as electron donor for sulfate reduction. We demonstrate effective zinc removal (7.2 mmol L⁻¹ d⁻¹) with low zinc effluent concentrations (0.65–8.8 μM) in a system combining sulfide generation by sulfate reducing bacteria (7.2–10.6 mmol SO₄²⁻ L⁻¹ d⁻¹) at low pH (5.5) with the bio-precipitation of crystalline sphalerite. To investigate the effect of the sulfide excess on the settling properties of the sphalerite precipitates, the sulfide excess concentration was varied about two orders of magnitude (0.008–2.2 mM). The results show that crystalline sphalerite was formed in all cases, but larger particles with better settling properties were formed at lower sulfide concentrations.     

A mutational analysis of receptor binding sites of interleukin-1{beta}:differences in binding of human interleukin-1{beta} muteins to human and mouse receptors

The 3-D crystal structure of interleukin-1ß(IL-1ß)has been used to define its receptor binding surface by mutationalanalysis. The surface of IL-1ß was probed by site-directedmutagenesis. A total of 27 different IL-1ß muteinswere constructed, purified and analyzed. Receptor binding measurementson mouse and human cell lines were performed to identify receptoraffinities. IL-1ß muteins with modified receptor affinitywere evaluated for structural integrity by CD spectroscopy orX-ray crystallography. Changes in six surface loops, as wellas in the C- and N-termini, yielded muteins with lower bindingaffinities. Two muteins with intact binding affinities showed10- to 100-fold reduced biological activity. The surface regioninvolved in receptor binding constitutes a discontinuous areaof 1000 Å2 formed by discontinuous polypeptide chain stretches.Based on these results, a subdivision into two distinct localareas is proposed. Differences in receptor binding affinitiesfor human and mouse receptors have been observed for some muteins,but not for wild-type IL-1ß. This is the first timea difference in binding affinity of IL-1ß muteinsto human and mouse receptors has been demonstrated     

Hydrolytic degradation of oligo(lactic acid): a kinetic and mechanistic study

This study shows that the degradation mechanism and kinetics of monodisperse oligo(lactic acid)s esterified with N-(2-hydroxypropyl)methacrylamide (HPMAm) are strongly influenced by the nature of the chain end. Oligomers with free hydroxyl chain ends degraded predominantly by chain end scission via a backbiting mechanism with a pseudo first-order rate constant k_bb=2.7 h⁻¹ in aqueous buffer (37 °C, pH 7.2). Once the hydroxyl groups were protected by acetylation, random chain scission became the rate limiting step with k_r=0.022 h⁻¹ under the same conditions. Using these rate constants, the theoretical time-resolved degradation profile was calculated for every (intermediate) degradation product and corresponded very well with the experimental results. The rate of formation of HPMAm was independent of the chain length for the acetylated oligomers, while the hydroxyl terminated oligomers with an even number of lactic acid units formed HPMAm more rapidly than oligomers with an odd number of units. The possibility to fine-tune the degradation rate is relevant when applied as e.g. hydrogels for controlled release or tissue engineering materials.     

CFD study of the minimum bubbling velocity of Geldart A particles in gas-fluidized beds

The minimum bubbling velocity, which demarcates the homogeneous and heterogeneous fluidization regimes, plays a pivotal role in gas fluidization of Geldart A particles. We systematically study the effect of gas and particle properties on the minimum bubbling velocity of Geldart A particles in gas-fluidized beds using both Eulerian–Eulerian and Eulerian–Lagrangian models. We find that the minimum bubbling velocities as obtained from the simulations are in reasonable agreement with the well-known experimental correlation of Abrahamsen and Geldart (Powder Technology, 1980, 26: 35–46). To our best knowledge, this is the first time that the minimum bubbling velocity is correctly predicted by Eulerian–Eulerian models, without using an artificial ad-hoc modification of the gas–solid interaction force. Furthermore, we have performed a systematic investigation into the effect of the specific method that is used for determining minimum bubbling velocity. Our simulations show that the minimum bubbling velocity that would be obtained from the simulated bed contraction is larger than the one obtained from visual observation, which in its turn exceeds the one obtained from sudden change of standard deviation of pressure drop. We find that the abrupt change of the granular temperature with increasing superficial gas velocity may be a more suitable indicator for identifying the onset of heterogeneous fluidization.     

On a new formal proof model for RFID location privacy

We discuss a recently proposed formal proof model for RFID location privacy. We show that protocols which intuitively and in several other models are considered not to be location private, are provably location private in this model. Conversely, we also show that protocols which obviously are location private, are not considered location private in this model.Specifically, we prove a protocol in which every tag transmits the same constant message to not be location private in the proposed model. Then we prove a protocol in which a tag's identity is transmitted in clear text to be weakly location private in the model.