Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

Ophthalmologic findings in Usher syndrome type 2A

Thirty-seven patients, comprising 24 familial cases and 13 isolated patients with Usher syndrome type II (USH2), underwent ophthalmologic examination. Based on the degree of hearing loss, normal vestibular function, and gene-linkage analysis, familial cases were assumed to have USH2A. An analysis of genetic heterogeneity failed to reveal the presence of a second locus in the Dutch population. Although the patients appear to belong to a genetically homogeneous group, remarkable ophthalmologic variability was found. Corrected visual acuity decreased with age and remarkable differences in visual acuity were found within one family. Fundoscopic findings were classified as type A if attenuated vessels and bone corpuscles in all quadrants were found or as type B if findings other than these were found. The prevalence of type A significantly increased with age.     

Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in ABCA4

The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1.     

Attuning speech-enabled interfaces to user and context for inclusive design: technology, methodology and practice

This paper presents a methodology to apply speech technology for compensating sensory, motor, cognitive and affective usage difficulties. It distinguishes (1) an analysis of accessibility and technological issues for the identification of context-dependent user needs and corresponding opportunities to include speech in multimodal user interfaces, and (2) an iterative generate-and-test process to refine the interface prototype and its design rationale. Best practices show that such inclusion of speech technology, although still imperfect in itself, can enhance both the functional and affective information and communication technology-experiences of specific user groups, such as persons with reading difficulties, hearing-impaired, intellectually disabled, children and older adults.

Numerical investigation of cyclic variations in gasoline engines using a hybrid URANS/LES modeling approach

Cycle to cycle variations are an important aspect in the development and optimization process of internal combustion engines. In this study the feasibility of using a detached eddy simulation (DES) SST model, which is a hybrid URANS/LES model, to predict cycle to cycle variations is investigated. In the near wall region or in regions where the grid resolution is not sufficiently fine to resolve smaller structures, the two-equation RANS shear-stress transport (SST) model is used. In the other regions with higher grid resolution an LES model is applied. First, the numerical requirements associated with the hybrid URANS/LES and the employed solver are studied in detail. The numerical dissipation of the spatial scheme and the choice of the temporal scheme including the step size are evaluated. In addition, the accuracy of the solver for moving meshes, which are required for engine calculations, is assessed. The modeling constant linking the grid size to the DES filter length scale is determined by calculating a decaying homogeneous isotropic turbulence test case for different grid resolutions. The final applications of the model are two different engine cases with increasing complexity. The first case is the statistically stationary flow through an engine intake port. The time resolved flow structure predicted by the DES SST model is analyzed and the resulting time-averaged velocity fields are compared to experimental data at different locations. The second application is a motored multi-cycle simulation of a series production engine. The instantaneous flow development during the intake and compression stroke of one single cycle is studied and the ensemble-averaged and the instantaneous velocity fields as well as the resolved velocity fluctuations are compared to optical measurements. Special emphasis is placed on the cyclic differences of the velocity fluctuations at the time of ignition in the vicinity of the spark plug and the expected influence on the combustion process.     

Estimating body shape of dressed humans

The paper presents a method to estimate the detailed 3D body shape of a person even if heavy or loose clothing is worn. The approach is based on a space of human shapes, learned from a large database of registered body scans. Together with this database we use as input a 3D scan or model of the person wearing clothes and apply a fitting method, based on ICP (iterated closest point) registration and Laplacian mesh deformation. The statistical model of human body shapes enforces that the model stays within the space of human shapes. The method therefore allows us to compute the most likely shape and pose of the subject, even if it is heavily occluded or body parts are not visible. Several experiments demonstrate the applicability and accuracy of our approach to recover occluded or missing body parts from 3D laser scans.     

Non‐Rigid Puzzles

Shape correspondence is a fundamental problem in computer graphics and vision, with applications in various problems including animation, texture mapping, robotic vision, medical imaging, archaeology and many more. In settings where the shapes are allowed to undergo non‐rigid deformations and only partial views are available, the problem becomes very challenging. To this end, we present a non‐rigid multi‐part shape matching algorithm. We assume to be given a reference shape and its multiple parts undergoing a non‐rigid deformation. Each of these query parts can be additionally contaminated by clutter, may overlap with other parts, and there might be missing parts or redundant ones. Our method simultaneously solves for the segmentation of the reference model, and for a dense correspondence to (subsets of) the parts. Experimental results on synthetic as well as real scans demonstrate the effectiveness of our method in dealing with this challenging matching scenario.     

Integral invariants for shape matching

For shapes represented as closed planar contours, we introduce a class of functionals which are invariant with respect to the Euclidean group and which are obtained by performing integral operations. While such integral invariants enjoy some of the desirable properties of their differential counterparts, such as locality of computation (which allows matching under occlusions) and uniqueness of representation (asymptotically), they do not exhibit the noise sensitivity associated with differential quantities and, therefore, do not require presmoothing of the input shape. Our formulation allows the analysis of shapes at multiple scales. Based on integral invariants, we define a notion of distance between shapes. The proposed distance measure can be computed efficiently and allows warping the shape boundaries onto each other; its computation results in optimal point correspondence as an intermediate step. Numerical results on shape matching demonstrate that this framework can match shapes despite the deformation of subparts, missing parts and noise. As a quantitative analysis, we report matching scores for shape retrieval from a database.