Discovery of Novel Epoxyketone Peptides as Lipase Inhibitors

Obesity is the most common nutritional disorder in the developed world and is associated with important comorbidities. Pancreatic lipase (PL) inhibitors play a key role in the metabolism of human fat. A series of novel epoxyketones peptide derivatives were investigated for their pancreatic lipase inhibitory activity. The epoxyketone moiety is a well-known reactive electrophile group that has been used as part of proteasome inhibitors in cancer therapy, and it is widely believed that these are very selective for targeting the proteasome active site. Here we investigated various peptide derivatives with an epoxide warhead for their anti-lipase activity. The assessment of these novel epoxyketones was performed by an in-house method that we developed for rapid screening and identification of lipase inhibitors using GC-FID. Herein, we present a novel anti-lipase pharmacophore based on epoxyketone peptide derivatives that showed potent anti-lipase activity. Many of these derivatives had comparable or more potent activity than the clinically used lipase inhibitors such as orlistat. In addition, the lipase appears to be inhibited by a wide range of epoxyketone analogues regardless of the configuration of the epoxide in the epoxyketone moiety. The presented data in this study shows the first example of the use of epoxyketone peptides as novel lipase inhibitors.     

Palladium extraction by triphenylphosphine sulfide in benzene

The extraction of Pd(II) by triphenylphosphine sulfide (Ph₃PS) in benzene from nitric acid solutions has been investigated. The effect of different parameters on the extraction of palladium was studied. Based on the results, an equilibrium model is proposed. The stoichiometry of the extracted species was elucidated and found to be Pd(NO₃)₂2Ph₃PS. Possible interference with selected radionuclides that might exist in high level liquid waste was investigated and discussed.     

Characterization by mirage effect technique of dye diffusion in columnar discotic liquid crystals

The anisotropic behaviour of the matter diffusion in columnar discotic liquid crystals is studied by the 'mirage effect' technique. The D_h and D₀ mesophases of C₈HET and C₁₁HET, respectively, are considered. The impurity (a dye, the 1-[4-(xylylazo)xylylazo]-2-naphthol) diffusing in these mesophases is detected by the photothermal deflection technique. Measurements of the diffusion coefficients are performed in two perpendicular directions, along and perpendicularly to the molecular columns. Effects of impurity size, length and type of the branched chains on the discs of triphenylene, and molecule stackings in columns, are presented.     

Dielectric Properties of Polyimide‐Mica Hybrid Films

Summary: Polyimide‐mica hybrid films were prepared via ultrasonic dispersion and in situ polymerization process from a solution of a polyimide precursor and mica in N,N‐dimethylacetamide, and their structure was characterized by FTIR and XRD techniques. The dependence of dielectric properties, such as dielectric constant and electrical breakdown strength, of the hybrid films on the content of mica was studied at room and cryogenic temperatures. The results show that the dielectric constant of PI‐mica hybrid films decreases with the increase of the mica content at temperatures from −150 to 150 °C and at frequency range from 1 kHz to 1 MHz. It was found that the cryogenic electrical breakdown strength of the PI‐mica hybrid films could meet the requirements of cryogenic insulating materials.

Effect of frequency on the dielectric constant of PI‐mica hybrid films at 140 °C at the frequency from 1 kHz to 1 MHz.     

A New Versatile Water‐Soluble Iniferter Platform for the Preparation of Molecularly Imprinted Nanoparticles by Photopolymerisation in Aqueous Media

The multi‐step synthesis of a new water‐soluble dithiocarbamate iniferter platform for the preparation of nanoparticles and ‐gels in aqueous solvents by photoinduced living‐radical polymerisation is described herein. The water solubility of the dithiocarbamate iniferter was achieved by incorporating two unprotected glucose units into the iniferter structure by copper(I)‐catalysed azide–alkyne cycloaddition (“click chemistry”). Molecularly imprinted nanoparticles (MIPs) specific for 2,4‐dichlorophenoxyacetic acid and the corresponding non‐imprinted particles (NIPs) were prepared in pure water by using the prepared iniferter as photoinitiator. Radioligand binding tests confirmed a high imprinting factor, and the living character of the iniferter was demonstrated by re‐initiating a second photochemical polymerisation on the NIP nanoparticles in water by using ethylene glycol methacrylate phosphate. Our newly synthesised structure is a promising tool for iniferter‐mediated photopolymerisations in aqueous media for the preparation of biocompatible nanomaterials with high potential for biomedical applications in a bottom‐up fashion.     

Entangled phase states via quantum beam splitter

We study the entanglement effect of beam splitter on the temporally stable phase states. Specifically, we consider the eigenstates (phase states) of a unitary phase operator resulting from the polar decomposition of ladder operators of generalized Weyl-Heisenberg algebras possessing finite dimensional representation space. The linear entropy that measures the degree of entanglement at the output of the beam splitter is analytically obtained. We find that the entanglement is not only strongly dependent on the Hilbert space dimension but also quite related to strength the parameter ensuring the temporal stability of the phase states. Finally, we discuss the evolution of the entangled phase states.     

The Behaviour of Nitrilimines Towards Ethyl Isocyanoacetate

Summary.  Interactions between nitrilimines and the title isocyanide afford, through two competing pathways, 2,3-dihydro-1,2,4-triazines and 1,3-oxazoles. In situ cycloaddition of unreacted nitrilimine with the triazines gives rise to a third class of products, the bicyclic 1,5,6,8a-tetrahydro[1,2,4]triazolo[4,3-d][1,2,4]triazines. Acceptor-free representatives of the latter are prone to triazine ring cleavage, yielding triazolyl ketone hydrazones which served as a structure proof. Substituent effects became apparent upon employment of N-(4-methoxyphenyl)- and N-(4-nitrophenyl)nitrilimines: whereas the former afforded a quinoxaline as the fourth product, triazine formation was totally blocked with the latter, the corresponding oxazole being the sole product. The constitution of acceptor-substituted bicyclic compounds (which failed to give the structure-revealing hydrazones) was established by an X-ray diffraction analysis. Corresponding author. E-mail: d.moderhack@tu-bs.de Received March 5, 2002; accepted March 19, 2002     

On equilibrium analysis of acyclic multiclass loss networks under admission control

We consider equilibrium analysis of several dynamic resource sharing policies for multiclass loss networks with acyclic topologies. The policies of interest are based on the principle of prioritizing classes via thresholding or reservation. We show that under each policy the equilibrium network state is a Markov random field and we obtain closed form expressions for the conditional probabilities therein. Such representations drastically reduce the computational complexity of blocking probability and revenue calculations. We provide revenue comparison of the considered policies and several extensions of the applied analytical technique.     

On the Nilpotency Class of a Generalized 3-Abelian Group

A group G is called 3-abelian if the map ${x \mapsto x^{3}}$ is an endomorphism of G and it is called generalized 3-abelian, if there exist elements ${c_{1}, c_{2}, c_{3} \in G}$ such that the map ${\varphi : x \longmapsto {x^{c_{1}} x^{c_{2}} x^{c_{3}}}}$ is an endomorphism of G. Abdollahi, Daoud and Endimioni have proved that a generalized 3-abelian group G is nilpotent of class at most 10. Here, we improve the bound to 3 and we show that the exponent of its derived subgoup is finite and divides 9. We also prove that G is 3-Levi, 9-central, 9-abelian and 3-nilpotent of class at most 2.