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Background: Acute pancreatitis (AP) is a serious, mechanistically not entirely resolved side effect of L-asparaginase-containing treatment for acute lymphoblastic leukemia (ALL). To find new candidate variations for AP, we conducted a genome-wide association study (GWAS). Methods: In all, 1,004,623 single-nucleotide variants (SNVs) were analyzed in 51 pediatric ALL patients with AP (cases) and 1388 patients without AP (controls). Replication used independent patients. Results: The top-ranked SNV (rs4148513) was located within the ABCC4 gene (odds ratio (OR) 84.1; p = 1.04 × 10−14). Independent replication of our 20 top SNVs was not supportive of initial results, partly because rare variants were neither present in cases nor present in controls. However, results of combined analysis (GWAS and replication cohorts) remained significant (e.g., rs4148513; OR = 47.2; p = 7.31 × 10−9). Subsequently, we sequenced the entire ABCC4 gene and its close relative, the cystic fibrosis associated CFTR gene, a strong AP candidate gene, in 48 cases and 47 controls. Six AP-associated variants in ABCC4 and one variant in CFTR were detected. Replication confirmed the six ABCC4 variants but not the CFTR variant. Conclusions: Genetic variation within the ABCC4 gene was associated with AP during the treatment of ALL. No association of AP with CFTR was observed. Larger international studies are necessary to more conclusively assess the risk of rare clinical phenotypes.

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia-cell entry into the CNS using a primograft ALL mouse model. We found that primary ALL cells transplanted onto nonobese diabetic/severe combined immunodeficiency mice faithfully recapitulated clinical and pathological features of meningeal infiltration seen in patients with ALL. ALL cells that had entered the CNS and were infiltrating the meninges were characterized by high expression of vascular endothelial growth factor A (VEGF). Although cellular viability, growth, proliferation, and survival of ALL cells were found to be independent of VEGF, transendothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia-cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia on in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL-cell entry into the CNS, which by targeting VEGF signaling may serve as a novel strategy to control CNS leukemia in patients, replacing conventional CNS-toxic treatment.

Contains fulltext : 207610.pdf (Publisher’s version ) (Closed access) BACKGROUND: Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6-RUNX1 fusion sites as a single marker for MRD quantification. PROCEDURE: In a representative, uniformly treated cohort of pediatric relapsed ALL patients (n = 52), ETV6-RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements. RESULTS: Primer/probe sets designed to ETV6-RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10(-4) compared to the gold standard with 100% and 73% versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6-RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P < .01) with differences >(1/2) log-step in only 6% of patients. A high proportion of ETV6-RUNX1-positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup. CONCLUSIONS: ETV6-RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front-line and second-line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6-RUNX1 fusion can be used as single MRD marker.

In systemic light chain amyloidosis, an overexpressed antibody light chain (LC) forms fibrils which deposit in organs and cause their failure. While it is well-established that mutations in the LC’s VL domain are important prerequisites, the mechanisms which render a patient LC amyloidogenic are ill-defined. In this study, we performed an in-depth analysis of the factors and mutations responsible for the pathogenic transformation of a patient-derived λ LC, by recombinantly expressing variants in E. coli. We show that proteolytic cleavage of the patient LC resulting in an isolated VL domain is essential for fibril formation. Out of 11 mutations in the patient VL, only one, a leucine to valine mutation, is responsible for fibril formation. It disrupts a hydrophobic network rendering the C-terminal segment of VL more dynamic and decreasing domain stability. Thus, the combination of proteolytic cleavage and the destabilizing mutation trigger conformational changes that turn the LC pathogenic., eLife digest Amyloid light chain amyloidosis, shortened to AL amyloidosis, is a rare and often fatal disease. It is caused by a disorder of the bone marrow. Usually, cells in the bone marrow produce Y-shaped proteins called antibodies to fight infections. In AL amyloidosis, these cells release too much of the short arm of the antibody, known as its light chain, and the light chains also carry mutations. The antibodies are no longer able to assemble properly, and instead misfold and form structures, known as amyloid fibrils. The fibrils build up outside the cells, gradually causing damage to tissues and organs that can lead to life-threatening organ failure. Due to the rareness of the disease, diagnosis is often overlooked and delayed. People experience widely varying symptoms, depending on the organs affected. Also, given the diversity of antibodies people make, every person with AL amyloidosis has a variety of mutations implicated in their disease. It is thought that mutations in the antibody light chain make it unstable and prone to misfolding, but it remains unclear which specific mutations trigger a cascade of amyloid fibril formation. Now, Kazman et al. have pinpointed the exact mechanism in one case of the disease. First, tissue biopsies from a woman with advanced AL amyloidosis were analyzed, and the defunct antibody light chain was isolated. Eleven mutations were identified in the antibody light chain, only one of which was found to be responsible for the formation of the harmful fibrils. The next step was to determine how this one small change was so damaging. The experiments showed that after the antibody light chain was cut in two, a process that happens naturally in the body, this single mutation transforms it into a protein capable of causing disease. In this ‘bedside to lab bench’ study, Kazman et al. have succeeded in determining the molecular origin of one case of AL amyloidosis. The results have also shown that the instability of antibodies due to mutation does not alone explain the formation of amyloid fibrils in this disease and that the cutting of this protein in two is also important. It is hoped that, in the long run, this work will lead to new diagnostics and treatment options for people with AL amyloidosis.

Spatially resolved rocking curve imaging has been used to analyze laterally overgrown silicon layers grown by liquid phase epitaxy. We were able to study both the overgrown layer as well as the strain fluctuations of the Si substrate underneath by means of a tabletop x-ray topographic setup. The strain-field analysis reveals relative changes of the lattice parameter up to 3.5×10-6 in the silicon substrate underneath the overgrown layer in particular regions and a down bending of both wings of the epitaxial overgrown layers. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The spatial resolution of an imaging system is most often experimentally determined by using model objects and idealized imaging conditions. This traditional approach does not properly take into account the influence of noise and the dependence of contrast on the object. The latter influence is essential especially in the case of magnified X-ray images acquired by two fold asymmetric Bragg diffraction. For this phase sensitive technique the application of a criterion for spatial resolution based upon Fourier analysis is shown to provide reliable resolution values in a simple way, overcoming the limitations mentioned above. For the case of Bragg-magnified imaging of an ant leg with 166 fold magnification (effective pixel size 0.094 μm), the physical resolution achieved in the image is found to be 0.4 μm.

X-ray diffuse scattering from a 17-fold InGaAs/GaAs quantum dot (QD) multilayer grown by an advanced molecular beam epitaxy process was investigated. The QDs in each layer form extended chains that are oriented along the [110] planar direction. A prominent three-dimensional satellite structure in the x-ray diffuse scattering is found, which is caused by a strong lateral chain-chain correlation and vertical correlation of the lateral chain positions in the multilayer. In contrast, the dot-dot correlation within the chains are comparatively small. Numerical x-ray scattering simulations have been carried out. A comparison with corresponding experimental intensity patterns provides information on the QD size and QD spatial distribution.

The plastic relaxation of SiGe/Si is closely related to the nucleation of misfit dislocations at early stages. We have investigated the very early stages at annealing temperatures ranging from 520°C to 670°C by means of x-ray topography (XRT), atomic force microscopy (AFM) and transmission electron microscopy. At misfit dislocation densities within the range accessible by XRT, i.e. up to about 1000 cm−1, dislocations bundles predominate. This is verified by AFM and is explained by heterogeneous nucleation. The fewer the dislocations that are contained within dislocation bundles the rarer the blocking and cross slip that are observed. It is demonstrated that laser heating increases the number of nucleation centres drastically and is well suited to induce nucleation at selected sites. Furthermore, these nucleation centres provide dislocation bundles containing only a few dislocations. In contrast to this, implantation can produce defects that stop dislocation propagation quite effectively at the comparatively low temperatures used in our experiments.

Summary The pseudopilin PulG is one of several essential com- ponents of the type II pullulanase secretion machin- ery (the Pul secreton) of the Gram-negative bacterium Klebsiella oxytoca . The sequence of the N-terminal 25 amino acids of the PulG precursor is hydrophobic and very similar to the corresponding region of type IV pilins. The structure of a truncated PulG (lacking the homologous region), as determined by X-ray crystallography, was found to include part of the long N-terminal a -helix and the four internal anti-parallel b - strands that characterize type IV pilins, but PulG lacks the highly variable loop region with a disulphide bond that is found in the latter. When overproduced, PulG forms flexible pili whose structural features, as visu- alized by electron microscopy, are similar to those of bacterial type IV pili. The average helical repeat com- prises 17 PulG subunits and four helical turns. Elec- tron microscopy and molecular modelling show that PulG probably assembles into left-handed helical pili with the long N-terminal a a a -helix tightly packed in the centre of the pilus. As in the type IV pilins, the hydro- phobic N-terminal part of the PulG a -helix is neces- sary for its assembly. Subtle sequence variations within this highly conserved segment seem to deter- mine whether or not a type IV pilin can be assembled into pili by the Pul secreton.

X-ray diffuse scattering is used to probe size, shape, and strain distribution of self-organized SiGe∕Si(001) islands, which were grown by liquid phase epitaxy. The SiGe islands show a truncated pyramidal shape with {111} side facets and a (001) top facet and they are highly uniform in size. With an averaged island base width of 130nm and a corresponding height of 65nm all the islands have a characteristic geometrical base-to-height aspect ratio of about 2. X-ray diffuse scattering is used to locally probe the elastically relaxed regions inside the island apex and the strongly strained regions near the substrate-island interface. It is found that the geometrical aspect ratio has a large impact on the x-ray diffuse intensity pattern in reciprocal space. By performing corresponding kinematical x-ray simulations this fact can be utilized to determine the aspect ratio with high sensitivity.

We report on structural investigations on multi-fold stacks of In 0.6 Ga 0.4 As quantum dots (QDs) embedded within a GaAs matrix. The structures have been grown by means of metalorganic chemical vapor deposition. Cross-sectional transmission electron micrographs prove a pronounced vertical QD correlation, while plan-view images do not show any lateral ordering. Grazing incidence diffraction within various crystallographic zones clearly reveal a QD shape with a four-fold symmetry. Comparing dynamical scattering simulations, which base on finite element calculations for the strain field show that the shape of the QDs can be described by a prism with a flat top on a thin wetting layer. The mean lateral dot distance evaluated from diffuse X-ray scattering agrees well with the QD density estimated from TEM plan-view images.

In the present paper we report on structural investigations of fivefold In0.2Ga0.8As/GaAs superlattices which have been grown by means of metal organic chemical vapor deposition on vicinal GaAs(001) substrates. Cross-sectional transmission electron micrographs exhibit an initially flat and nonfaceted grooved surface, while step bunching occurs during subsequent growth stages with an inclined vertical inheritance approximately 45° off the (001) direction. A reconstructed sample cross section on the base of high resolution x-ray diffraction data qualitatively confirms the local morphology proved by transmission electron microscopy. Moreover, a line shape analysis of diffusely scattered intensity using Gauss profiles indicates a lateral short range ordering of step bunches.

Legionella pneumophila, the etiological agent of Legionnaires' disease, is an environmental pathogen. In natural and man-made aquatic habitats legionellae multiply intracellularly within free-living protozoa (1, 2, 12). Human infection occurs by inhalation of aerosolized bacteria. During the colonization of the respiratory tract, Legionella enters and replicates within human alveolar macrophages and epithelial cells (6, 12, 33). In recent years, much progress has been made toward identifying specific virulence factors of Legionella. In addition to surface factors, secretion systems, iron acquisition determinants, and other factors, the Mip (macrophage infectivity potentiator) protein has been shown to contribute to survival of Legionella in different cell lines and to virulence in guinea pigs (4, 5, 48, 51). The Legionella Mip is a basic 24-kDa protein (pI 9.8). It possesses an N-terminal signal sequence, which is cleaved off while the protein is transported through the cytoplasmic membrane (51), and finally the protein is found on the surface of Legionella cells (17). Mip exhibits a peptidylprolyl cis/trans isomerase (PPIase) activity and belongs to the enzyme family of FK506-binding proteins (FKBP) (10, 11, 42). Mip-like proteins or corresponding genes were also identified in other microorganisms, such as Chlamydia trachomatis (24), Chlamydia psittaci (40), Coxiella burnetii (30), Trypanosoma cruzi (31), and Escherichia coli (18). The addition of PPIase inhibitors such as FK506 or rapamycin to C. trachomatis and T. cruzi resulted in reduced infectivity of these organisms (25, 31). Mip-negative mutants of Legionella were approximately 10- to 100-fold less infective for Acanthamoeba castellanii and human mononuclear phagocytes than were their isogenic Mip-positive parental strains (51). Mip-negative mutants are also less infective for Hartmannella vermiformis and lung epithelial cells (5, 6). Site-specific Legionella mutants with strongly reduced PPIase activity exhibited wild-type growth rates in cell culture assays. However, it could not be determined whether the residual PPIase activity was sufficient for the virulent phenotype of the mutants (51). Comparison of the primary structures showed that Mip-like proteins consist of a C-terminal FKBP-homologous domain and an N-terminal extension of 100 to 150 amino acid residues (43). Cross-linking experiments with dimethyl pimelimidate (DMP) revealed that Legionella Mip forms homodimers both in solution and on the bacterial surface (43, 44). In this respect the Legionella protein resembles FKBP22 and FkpA from E. coli, which were also shown to form dimers in solution (35, 36). More recently, the 2.4-A crystal structure of the Mip protein from L. pneumophila Philadelphia 1 was determined (39). This study revealed that the Mip monomer consists of an N-terminal dimerization module, a very long connecting α-helix (α3), and a C-terminal PPIase domain. Formation of the nonglobular, V-shaped homodimer is mediated by an unusual four-helix bundle, involving two helices from the N-terminal domain of each monomer. The exact function of Legionella Mip in vivo remains to be established. The hypothesis that the PPIase activity of Mip contributes to virulence is still justified since the residual PPIase activity of site-specifically altered Mip proteins may be sufficient to induce functional effects in eukaryotic cells (51). It has also to be considered that the enzymatic activities observed in vitro do not reflect the activity towards the putative in vivo substrate. Furthermore, it was recently demonstrated that specific monoclonal antibodies which block the PPIase active site of Mip in vitro reduced the infectivity of Legionella in A. castellanii and U937 cells (J. H. Helbig, unpublished data). With the determination of the three-dimensional structure of Legionella Mip, a more rational starting point for functional analysis of this protein has been established. In this respect, two features of Mip appear to be prominent: (i) the N-terminal dimerization domain and (ii) the PPIase activity which is located in the C-terminal domain. Since the role of the homodimeric state of Legionella Mip is still unclear, we constructed and analyzed N-terminally truncated, monomeric Mip variants and tested their enzymatic properties. In addition, we studied the infection of A. castellanii and guinea pigs with these variants and previously established PPIase mutants.

We have investigated the x-ray intensity distribution around 220 reciprocal lattice point in case of grazing incidence diffraction at SiGe nanoscale free-standing islands grown on Si(001) substrate by LPE. Experiments and computer simulations based on the distorted wave Born approximation utilizing the results of elasticity theory obtained by FEM modelling have been carried out. The data reveal fine structure in the distribution of scattered radiation with well-pronounced maxima and complicated fringe pattern. Explanation of the observed diffraction phenomena in their relation to structure and morphology of the island is given. An optimal island model including its shape, size and Ge spatial distribution was elaborated.

The different properties of laboratory- and synchrotron-based double-crystal setups for X-ray topographic applications are discussed as a basis for the realization of a versatile instrument allowing the investigation of all kinds of crystals with high strain sensitivity and without any reduction in image size. It appears that the use of a bendable highly perfect monochromator (silicon) achieves this goal, through the local adaptation of Bragg angles, to compensate either dispersion or a bending of the sample.

We report on free-standing InP quantum dots grown on (0 0 1) InGaP/GaAs which exhibit a pronounced size anisotropy with respect to the [ 1 1 0 ] and [ 1 1 0 ] directions. X-ray diffuse scattering together with respective kinematical simulations using elasticity theory makes it possible to determine with high accuracy the geometric aspect ratios of island height and island base widths. The influence of these ratios on the strain field inside the quantum dots will be discussed.

We highlight the great potential of x-ray diffuse scattering for the characterization of mesoscopic structures. The mesoscopic length scale plays a fundamental role at semiconductors, since structures with spatial dimensions in the nanometer regime exhibit quantum size effects. Also the driving forces during epitaxial growth of these structures are most relevant at mesoscopic length scales and they may lead to self-organization processes in that structures can form spontaneously during epitaxial growth. One of the most interesting features are quantum dots (QDs) since they exhibit zero-dimensional electronic properties and thus show an impressive potential for applications in optoelectronic devices. X-ray diffuse scattering is an excellent tool to investigate shape, size, and positional correlation and to characterize the strain field inside and in the vicinity of such self-organized mesoscopic structures. It provides non-destructive structural information over the entire mesoscopic length scale. X-ray scattering is complementary to direct imaging techniques in that it gives a statistical average over large ensembles with high strain sensitivity. The application of different scattering techniques for the structural characterization of mesoscopic structures will be demonstrated. For the example of SiGe islands on Si (001) substrate it will be shown that x-ray diffuse scattering is able to reveal details of germanium distribution in such islands. In a second example the investigation of the asymmetric shape and size of InP QDs that are grown on (001) In0.48Ga0.52 P/GaAs is described. The influence of positional correlation on the diffuse scattering will be discussed.

This chapter focuses on the major infectivity potentiator protein (Mip) protein and the function and expression of the flagellum of Legionella pneumophila. The Mip protein forms a homodimer on the bacterial surface; each monomer consists of a proximal and a peripheral domain. The contact regions between the two monomers seem to be located at the N-terminal part of the protein. Motility is an important factor to find a new host for another cycle of intracellular replication and for colonization of new habitats. Flagellated bacteria have been found in lung alveolar spaces of patients with legionellosis. It was shown that expression of the virulent phenotype and motility is regulated coordinately. A gentamicin infection assay revealed a clear difference in the number of intracellular bacteria at the onset of multiplication. L. pneumophila is found in very different habitats and it is able to replicate intracellularly in many host cells. Researchers recently demonstrated that regulation of fiaA expression is modulated by different environmental factors, such as temperature, growth phase, osmolarity, viscosity, and the nutrient stage.

Planar ordering of dense self-organized arrays of InP/In 0.48 Ga 0.52 P quantum dots is investigated using grazing incidence small-angle X-ray scattering (GISAXS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). Using the two-dimensional Fourier transform of the AFM data together with the GISAXS data, we show that the degree of ordering increases with increasing InP deposition time and, therefore, with increasing quantum dot density. This increase in ordering is seen both in that the dot period is less variable and in the appearance of longer ranged ordering of the dots on the surface. Intense photoluminescence due to radiative recombination of heavy holes and electrons in the quantum dots is observed at an energy between the band gaps of InP and In 0.48 Ga 0.52 P. ( 2000 Elsevier Science B.V. All rights reserved.

The gene encoding the green fluorescent protein (GFP) was used as a reporter gene in Legionella pneumophila. To analyze GFP expression in Legionella, transcriptional fusions of gfp with the Legionella-specific mip (Macrophage Infectivity Potentiator) promoter (P(mip)) and the sod (SuperOxide Dismutase) promoter (P(sod)) derived from Listeria monocytogenes were constructed. Following transformation into the virulent L. pneumophila strain JR 32, strong GFP-mediated fluorescence was detected with both plasmids, although the sod promoter was associated with a 1ten-fold higher intensity. No fluorescence was observed in L. pneumophila transformed with the promoterless gfp gene. Comparison of fluorescence yields between various L. pneumophila strains that differ in their virulence characteristics and were transformed with the P(mip)-gfp carrying plasmid revealed no differences in GFP expression. Infection studies using Acanthamoeba castellanii as host and recombinant L. pneumophila strains carrying the P(mip)-gfp and P(sod)-gfp fusions indicated that the mip promoter was expressed when the bacteria replicated intracellularly. GFP expression was also used to monitor, in infected A. castellanii cells, the intracellular survival of, and incidence of host-cell killing by. L. pneumophila strains that vary in their virulence properties. As quantified by flow cytometry the highly virulent L. pneumophila strain Corby was twice as infectious to A. castellanii as the Philadelphia strain JR 32. Using the avirulent Philadelphia derivative 25D invasion but no intracellular multiplication was observed. In addition, we examined by flow cytometry the influence of cytochalasin D, cycloheximide, and methylamine on the uptake of Legionella by A. castellanii. In conclusion, gfp appears to be a convenient reporter gene whose expression in Legionella can be followed in real time and allows analysis of promoter activities in Legionella and monitoring of the infection process.

Self-organized CdSe/ZnSe quantum dots (QDs) were investigated by means of transmission electron microscopy (TEM). Plan-view diffraction contrast images each obtained under individual diffraction conditions showed different contrast behaviour. Bright-field imaging of single dots revealed circle-like contrast features. In the 040 dark-field image a 2-fold symmetry and in the 220 dark-field image a nearly 4-fold symmetry of the contrast features were observed. Supplementary strain-field calculations using a finite-element method were compared with the experimental contrast features. The distributions of the several strain components chosen according to the certain diffraction conditions show the same symmetry and orientation as the experimental features.

Constant-time 3D heteronuclear relayed E.COSY [Schmidt et al. (1996) J. Biomol. NMR, 7, 142–152], as based on generic 2D small-flip-angle HMQC-COSY [Schmidt et al. (1995) J. Biomol. NMR, 6, 95–105], has been modified to allow for quantitative determination of heteronuclear three-bond 3 J(Hα,Cγ) couplings. The method is applicable to amino acid spin topologies with carbons in the γ position which lack attached protons, i.e. to asparagine, aspartate, and aromatic residues in uniformly 13C-enriched proteins. The pulse sequence critically exploits heteronuclear triple-quantum coherence (HTQC) of CH2 moieties involving geminal Hβ proton pairs, taking advantage of improved multiple-quantum relaxation properties, at the same time avoiding scalar couplings between those spins involved in multiple-quantum coherence, thus yielding E.COSY-type multiplets with a splitting structure that is simpler than with the original scheme. Numerical least-squares 2D line-shape simulation is used to extract 3 J(Hα,Cγ) coupling constants which are of relevance to side-chain χ1 dihedral-angle conformations in polypeptides. Methods are demonstrated with recombinant 15N,13C-enriched ribonuclease T1 and Desulfovibrio vulgaris flavodoxin with bound oxidized FMN.

The characterization of the AlAs\GaAs multilayers based on the modelling of the X-ray scattering is discussed. The structural parameters regarding the thickness of the bilayer components and the vertical and lateral variations (interface roughness) were assessed from low and high angle scan modes. The diffuse scattering analysis showed that both lateral and vertical correlation of the interface roughness develops in this LPOMVPE grown system.

Highly regular islands of strained Si1-xGex have been grown on Si (001) by liquid phase epitaxy (LPE). The islands themselves are {111}-faceted truncated pyramids with a narrow base-width size distribution and coherent behaviour. In this study we report on the state of lateral ordering within a single layer of Si1-xGex islands. Grazing incidence small-angle x-ray scattering (GISAXS) was used to investigate the ordering as a function of island coverage. At very low island coverage the array behaves like a two-dimensional liquid exhibiting an increased number of island dimers which orient along the island base diagonal 100. On increasing the coverage these dimers develop into extended chains of islands oriented along 100. At high coverage there is strong ordering along both the 100 and the 110 directions. The self-organised ordering can be explained by two possible mechanisms: (i) that the observed ordering is driven by the anisotropy of the elastic constants where short-range order along the soft 100 directions is expected, and (ii) that there is an underlying two-dimensional ripple pattern in the wetting layer aligned along the 100 directions. At later stages of growth this pattern transforms into pseudomorphic islands.

Characteristics of the interface roughness in a low-pressure organometallic vapour phase epitaxy (LPOMVPE) grown AlAs/GaAs multilayer are studied by grazing-incidence x-ray scattering. Quantitative results are obtained by comparing experimental and theoretically calculated diffuse scattering maps. These corroborate with the features resolved by atomic force microscopy. The observed morphological features are discussed in the following sections.

We have investigated pseudomorphic ${\mathrm{Si}}_{1\ensuremath{-}x}{\mathrm{Ge}}_{x}$ layers grown on Si (001) by means of liquid-phase epitaxy. The layers have been grown in Stranski-Krastanov growth mode and consist of coherent {111}-faceted truncated pyramids exhibiting unique shape and a narrow size distribution. Samples with different spatial island densities, i.e., different mean island-island distances, have been investigated by means of grazing incidence small-angle x-ray scattering (GISAXS) and atomic force microscopy (AFM). We found initial stages of developing ordering of the island array at very low island densities, which is manifested as island dimers oriented along the island base diagonal 〈100〉. At medium densities extended chains of islands along 〈100〉 appear; however, also increased ordering along 〈110〉 could be observed. At high island densities there is strong ordering along both 〈100〉 and 〈110〉 directions. There are interesting differences in the GISAXS intensity profiles along these two directions. The close relationship between GISAXS and AFM power spectra is discussed.

Most inpainting approaches require a good image model to infer the unknown pixels. In this work, we directly learn a mapping from image patches, corrupted by missing pixels, onto complete image patches. This mapping is represented as a deep neural network that is automatically trained on a large image data set. In particular, we are interested in the question whether it is helpful to exploit the shape information of the missing regions, i.e. the masks, which is something commonly ignored by other approaches. In comprehensive experiments on various images, we demonstrate that our learning-based approach is able to use this extra information and can achieve state-of-the-art inpainting results. Furthermore, we show that training with such extra information is useful for blind inpainting, where the exact shape of the missing region might be uncertain, for instance due to aliasing effects.

Physical review / B 56(16), 10469 - 10482 (1997). doi:10.1103/PhysRevB.56.10469, The features of surface and interface roughness in crystalline AlAs/GaAs superlattices grown by molecular beam epitaxy on vicinal (001) GaAs substrates are studied by grazing-incidence x-ray scattering (GIXS). The effects of different growth modes [step-flow or two-dimensional- (2D-) nucleation], different substrate preparations, and growth interruptions on the roughness are investigated. The results of GIXS are compared with atomic force microscopy (AFM) images of sample surfaces. For samples grown in the step-flow mode, both of the methods display a distinct anisotropy in the lateral size of roughness along the substrate miscut direction and perpendicular to it. The lateral correlation lengths given by GIXS correspond to the size of step bunches observed by AFM, while individual steps are resolved by AFM only. GIXS reveals also a strong interface-interface correlation or inheritance of roughness for all the samples which is not accessible by AFM. Moreover, the angle of inclination of the direction of this inheritance from the surface normal is found to be dependent on the growth conditions. Two effects in the skew inheritance have been observed by means of 2D mapping of GIXS in the reciprocal space: (i) in the direction of substrate miscut the angle of skew inheritance inverted its sign, (ii) in the direction perpendicular to the miscut a strongly skew inheritance appeared as an effect of growth interruptions. Conclusions concerning the improvement of GIXS experiments applied to the studies of multilayers are derived., Published by Inst., Woodbury, NY

The x-ray scattering from relaxed heteroepitaxial layers with the misfit dislocations randomly distributed at the interface between the layer and the substrate is analyzed theoretically and experimentally. The profiles of the x-ray-diffraction peaks and the reciprocal space maps of the intensity are measured and simulated for several heteroepitaxial structures in a wide range of dislocation densities. At large dislocation densities, the peak position is governed by the mean distortions and the peak width is due to the mean-square variations of the distortions. The peak widths calculated for uncorrelated distribution of dislocations exceed the widths of the peaks measured on the heteroepitaxial structures with large mismatch. It is shown that the spatial correlations of the dislocations reduce the peak width and explain the discrepancy. For small dislocation densities, the coherent and the diffuse components of the intensity are measured and simulated. It is shown that the position of the coherent peak does not follow the mean distortions. Satellites of the diffuse peak are observed and explained.

The peculiarities of high-resolution measurements in grazing-incidence diffraction (GID) are studied, both theoretically and experimentally. It is shown that complete discrimination between coherent reflection and diffuse scattering due to defects in GID requires a three-dimensional mapping of reciprocal space. These measurements can be performed using a combination of analyzer crystal and position-sensitive detector for angular analysis of scattered x-rays in mutually perpendicular planes. The equations for the resolution function of GID experiments are given and applied to the interpretation of GID measurements taken from an AlAs/GaAs superlattice. The discrimination of diffuse scattering due to interfacial roughness in the superlattice is demonstrated.

A theory of x-ray diffuse scattering from interface roughness in grazing-incidence diffraction ~GID! is presented. The theory assumes dynamical diffraction of x rays from perfect multilayers with the diffuse scattering from roughness calculated in the distorted-wave Born approximation. This permits the calculation of scattering due to roughness at all points on the diffraction curves, including the vicinity of the Bragg peaks. It is shown that the measurements of diffuse scattering in GID can provide information on atomic ordering at crystal interfaces which is not accessible by usual x-ray specular reflection and nonspecular x-ray scattering. The theory is found to be in good agreement to the two GID experiments carried out with an etched Ge surface and an AlAs/GaAs superlattice at the Cornell High-Energy Synchrotron Source and European Synchrotron Radiation Facility, respectively. In the case of the etched Ge surface, an anti-Yoneda dip in the diffuse scattering pattern at the Bragg peak and two symmetrical shoulders on the Bragg curve wings have been found and explained. In the case of the AlAs/GaAs superlattice, the diffuse scattering has been separated from GID by means of high-resolution measurements. A comparison between diffuse scattering in GID and diffuse scattering in grazing incidence far from the diffraction conditions has shown that the atomic ordering was preserved in the interface roughness, while it was partially destroyed in the surface roughness.

Shape and composition profiles of self-organized In0.6Ga0.4As∕GaAs quantum dots (QDs) were investigated using diffuse x-ray scattering of a fivefold QD stack. To reveal the QD morphology, numerical scattering simulations of QDs with different morphologies were performed based on three-dimensional strain fields calculated by the finite element methods. Comparing our simulations to the data, we proved that the In concentration increases from the wetting layer to the top of the quantum dots. Moreover, we conclude that the In concentration of the wetting layers is significantly lower than the average value in the QDs.

SiGe Stranski–Krastanow islands coherently grown on Si(001) substrates by liquid phase epitaxy are typically made of truncated pyramids with {111} side facets, whereas the persistent presence of an (001) top facet indicates an energetical disadvantage of complete pyramids compared to truncated ones. We attribute this to a surface minimization process during the island evolution under the assumption of isotropically distributed surface energies and stable island facets. For the presence of {111} side facets we have theoretically derived a final geometrical aspect ratio of island base versus island height of 1.96, which is in excellent agreement with the experimentally derived averaged value of 2.08±0.10 within a concentration window between 9% and 30% germanium.

Selective area liquid phase epitaxy of InP mesas has been performed on masked Si(001) substrates previously overgrown with InP by metalorganic chemical vapour deposition (MOCVD). The resulting mesas are bordered by very smooth crystal facets which are free of defects over typically 300 μm and exhibit an etch pit density of ≤1 × 104 cm−2. The X-ray rocking curve half width of the mesas amounts to 144 arcsec and the quantum efficiency is increased by two orders of magnitude as compared to the underlying InP buffer layer. Thermally induced strain is observed by triple X-ray analysis to relax anisotropically in perfect agreement with finite element analysis. These results are encouraging to use the selectively grown mesas as buffer layers for device structures to be grown in a subsequent MOCVD process step.

Threading dislocations in gallium arsenide and point defects in silicon were observed for the first time by X-ray topography under grazing-incidence diffraction conditions. A new type of contrast on polished surfaces has been resolved for single crystals with defects. The characteristics of grazing-incidence diffraction topography are discussed.

By means of X-ray double-crystal topography we have investigated silicon-on-insulator lamellae grown by liquid-phase epitaxy upon thermally oxidized silicon. The majority of the lamellae were free of extended defects. It is shown that the topographic contrasts of these lamellae are mainly due to vertical stress exerted by the lamellae onto the substrate. This is surprising because the aspect ratio (thickness/lateral dimension) is of the order of 10-2. Our first calculations lead us to estimate the stress to be around 10 N cm-2. A simple model, which may be assumed to apply in general for crystal growth on amorphous substrates, is described here. It relates the stress to an adhesive force, which acts during growth.

We report on the evolution of lateral ordering of SiGe nanoscale islands on Si(001), which have been grown by means of liquid phase epitaxy in the Stranski-Krastanow mode. Applying post-growth atomic force microscopy on different sample areas covered by different island densities, we could trace ex-situ the development of extended island chains along the 〈100〉-directions. The linear alignment happens by further nucleation of islands at the end of an already existing formation. Those direct observations will be discussed in terms of finite element strain energy calculations around various island configurations.

Background Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children and adolescents, accounting for 30% of all cases of malignancy in this age group. The cure rate of ALL is now above 80%. The clinical and biological characteristics of ALL that have been studied to date are of limited use in predicting the individual response. Newly developed methods for the assessment of minimal residual disease (MRD) are more helpful in this regard.

Motion blur due to camera shake is one of the predominant sources of degradation in handheld photography. Single image blind deconvolution (BD) or motion deblurring aims at restoring a sharp latent image from the blurred recorded picture without knowing the camera motion that took place during the exposure. BD is a long-standing problem, but has attracted much attention recently, cumulating in several algorithms able to restore photos degraded by real camera motion in high quality. In this paper, we present a benchmark dataset for motion deblurring that allows quantitative performance evaluation and comparison of recent approaches featuring non-uniform blur models. To this end, we record and analyse real camera motion, which is played back on a robot platform such that we can record a sequence of sharp images sampling the six dimensional camera motion trajectory. The goal of deblurring is to recover one of these sharp images, and our dataset contains all information to assess how closely various algorithms approximate that goal. In a comprehensive comparison, we evaluate state-of-the-art single image BD algorithms incorporating uniform and non-uniform blur models.