Influence of mismatch on the defects in relaxed epitaxial InGaAs/GaAs(100) films grown by molecular beam epitaxy

Thick (∼3 μm) films of InxGa1−xAs grown on GaAs(100) substrates, across the whole composition range, have been examined by transmission electron microscopy and double‐crystal x‐ray diffraction. The results were compared with the observed growth mode of the material determined by in situ reflection high‐energy electron diffraction in the molecular beam epitaxy growth system. The quality of the material degraded noticeably for compositions up to x∼0.5 associated with an increased density of dislocations and stacking faults. In contrast, improvements in quality as x approached 1.0 were correlated with the introduction of an increasingly more regular array of edge dislocations

Reflectance anisotropy spectra from Si δ-doped GaAs(001): Correlation of linear electro-optic effect with integrated surface field

Reflectance anisotropy spectroscopy (RAS) has been employed in situ to investigate the overlayer growth of GaAs onto submonolayer to one monolayer coverages of Si δ layers deposited on the GaAs(001)-c(4×4) surface. The intensity of RAS features, thought to arise from the linear electro-optic (LEO) effect, is found to vary with both the number of atoms in the Si δ layer and the position of the δ plane from the GaAs surface. Self-consistent solutions to Poisson’s equation are made to calculate the electric field in the near-surface region of the samples. The results show a direct correlation between the LEO intensity and the surface field averaged over the penetration depth of the incident radiation, in confirmation of the LEO model

The molecular beam epitaxial growth of GaAs/GaAs(111)B: doping and growth temperature studies

A series of investigations are presented which address various aspects of the growth, by molecular beam epitaxy, of n‐type (Si doped) on‐axis GaAs/GaAs(111)B. In situ characterization by reflection high‐energy electron diffraction has identified four surface phases on the static (zero growth rate) surface, and three reconstructions which occur, depending upon the substrate temperature, during growth. The n‐type doping properties of GaAs/GaAs(111)B epilayers have been compared with n‐GaAs/GaAs(100) structures. Hall effect and low‐temperature photoluminescence measurements have demonstrated that it is possible to dope GaAs/GaAs(111)B with Si in the 6×1014 to 1018 cm−3 range. A variable growth temperature study is also presented which examines the surface structural, electrical, optical, and surface morphological properties of n‐GaAs/GaAs(111)B grown in the 400 to 650 °C temperature range. The onset of electrical conduction, and optically active material, was found to be directly related to changes in the dynamic surface structure. The variable growth temperature study also revealed a temperature regime within which it was possible to significantly improve the surface morphology of on‐axis GaAs/GaAs(111)B structures whilst retaining good electrical and optical properties

Growth optimization of n‐type GaAs on GaAs(201) substrates

A study of the growth by molecular‐beam epitaxy of Si‐doped n ‐type GaAs on the GaAs(201) surface is presented. The motivation for attempting growth on this particular plane, apart from fundamental considerations, is in connection with an investigation of off‐axis transport in GaAs. The effects of growth temperature and doping on GaAs(201) and GaAs(100) samples have been compared using the Hall effect, low‐temperature photoluminescence (PL), and Nomarski interference contrast microscopy. These studies showed that the PL, onset of conduction, and mobility behavior were very similar for both orientations. It was possible to dope n‐GaAs/GaAs(201) reliably from NSi∼4×1014 to 6×1018 cm−3, the highest mobility of 96 000 cm2 V−1 s−1 measured at 77 K, being obtained for a sample doped at NSi∼4×1014 cm−3

Photoluminescence measurements for GaAs grown on Si(100) and Si(111) by molecular beam epitaxy

Photoluminescence measurements have been used to characterize Si‐doped GaAs layers, ranging in thickness from 1.1–8.1 μm, grown on Si(111) and misorientated Si(100) substrates by molecular beam epitaxy. 4.2 K PL spectra for GaAs/Si (100) show a strain‐induced splitting between the heavy and light hole valence bands which corresponds to a biaxial tensile stress of 2.8± 0.15 kbar acting on the GaAs layer. Similar measurements for GaAs/Si(111) indicate that the GaAs layer is subject to a biaxial tensile stress of 3.9±0.15 kbar at 4.2 K. Furthermore, the intensity and line shape of luminescence features for GaAs/Si(111) for the first time indicate a crystalline quality comparable with the best GaAs/Si(100) material

As/P exchange on InP(001) studied by reflectance anisotropy spectroscopy

Reflectance anisotropy spectroscopy (RAS) has been used to investigate the As/P exchange reaction for group V stabilized InP(001) surfaces exposed to As2 and/or P2, under molecular beam epitaxy conditions. By comparing RAS spectra taken before, during, and after As2 exposure it is possible to confirm that the As/P exchange reaction is exactly reversible over a range of temperatures from 420 to 560 °C. Time-resolved RAS measurements of the reaction rate, monitored at an energy of 2.65 eV, indicate that the activation energy for the exchange is 1.23±0.05 eV

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems. Methods: Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues. Results: Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T). Conclusion: Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement