Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

Prevalence of tobacco use in Eritrea: results from a noncommunicable disease risk factor survey.

The prevalence of noncommunicable diseases in Eritrea is increasing. Tobacco use is a recognized risk factor for most of these diseases, especially cardiovascular disease. No data have been published on tobacco use in Eritrea. The present study sought to establish the prevalence of tobacco smoking in Eritrea. The World Health Organization STEPwise approach was used for the survey, conducted in 2004 on a random national sample size of 2,460 subjects (response rate = 93.7%). The prevalence of tobacco smoking in the general population was 8.1%; the prevalence was 15% among men, compared with 0.6% among women. Prevalence rates were higher in those older than 45 years of age. The prevalence of tobacco smoking was higher among Muslims (11.4%) than Orthodox Christians (5.8%), and among alcohol drinkers (10.2%) than nondrinkers (6.6%). The majority of tobacco users (89.3%) used commercially available cigarettes. A study on knowledge, attitudes, and practices regarding tobacco use is needed to determine the behavioral factors leading to tobacco smoking among the vulnerable groups.     

Assessing the aptitude of vesicular volcanic rocks as pozzolanic sources for supplementary cementitious materials

Bulletin of Engineering Geology and the Environment - The research was conducted to verify two vesicular basalt deposits identified for pozzolanic sources. These are Wejerat site, in southern...     

Structure and properties of layer-by-layer self-assembled chitosan/lignosulfonate multilayer film

The formation of polycation chitosan, CS, with polyanion lignosulfonate, LGS, multilayer films based on layer-by-layer self-assembly method was investigated by several techniques. UV absorption spectra showed that the growth of both CS and LGS layers followed the exponential model. The film surface wettability was found alternated depending on the surface properties of these two materials because the contact angle is smaller for the CS layer and greater for the LGS layer while the surface free energy is known greater for the former and smaller for the latter. AFM images indicated that the surface roughness of these layers was in nanosize and was increased with the layer number due to the aggregation. The field emission scanning electron microscope photograph showed that the average thickness of each layer was about 5–6 nm.     

Naturally Inspired Peptide Leads: Alanine Scanning Reveals an Actin‐Targeting Thiazole Analogue of Bisebromoamide

Systematic alanine scanning of the linear peptide bisebromoamide (BBA), isolated from a marine cyanobacterium, was enabled by solid‐phase peptide synthesis of thiazole analogues. The analogues have comparable cytotoxicity (nanomolar) to that of BBA, and cellular morphology assays indicated that they target the actin cytoskeleton. Pathway inhibition in human colon tumour (HCT116) cells was explored by reverse phase protein array (RPPA) analysis, which showed a dose‐dependent response in IRS‐1 expression. Alanine scanning reveals a structural dependence to the cytotoxicity, actin targeting and pathway inhibition, and allows a new readily synthesised lead to be proposed.     

Extraction and transport of gold(III) using some acyl(aroyl)thiourea ligands and a crystal structure of one of the complexes

A number of acyl(aroyl)thiourea ligands were used for the extraction of gold(III). Extraction was observed with all the ligands under the experimental conditions employed. The same ligands were also employed for transport studies of gold(III) which was observed with only N,N-dibutyl-N′-benzoylthiourea. All other ligands resulted in the metal ion being present in the organic phase, but none in the receiving phase. A crystal structure of the ligand N,N-diethyl-N′-camphanylthiourea as its complex with Au(I) was obtained. The complex crystallizes in the monoclinic space group P2₁ with an R-factor of 1.5%. The coordination sphere around Au(I) shows a nearly linear arrangement of sulphur and chloride.     

Landslide characterization and distribution in northern Ethiopia: a case study from the Adishu area

Bulletin of Engineering Geology and the Environment - Landslides have resulted in large numbers of casualties and huge economic losses in the hilly and mountainous areas of the Ethiopian highlands....     

Parametric oscillation with squeezed vacuum reservoirs

Employing the quantum Hamiltonian describing the interaction of a two-mode light (signal–idler modes) generated by a non-degenerate parametric oscillator (NDPO) with two uncorrelated squeezed vacuum reservoirs (USVR), we derive the master and the Fokker–Planck equations. The corresponding Fokker–Planck equation for the Q-function is then solved employing a propagator method developed by K. Fesseha [J. Math. Phys. 33 2179 (1992)]. Making use of this Q-function, we calculate the quadrature fluctuations of the optical system. From these results we infer that the signal–idler modes are in squeezed states. When the NDPO operates below threshold we show that, for a large squeezing parameter, a squeezing amounting to a noise suppression approaching 100% below the vacuum level in one of the quadratures can be achieved.