Characteristics of Retinitis Pigmentosa Associated with ADGRV1 and Comparison with USH2A in Patients from a Multicentric Usher Syndrome Study Treatrush

In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann–Whitney U test, p = 0.13); the mean age when 50% of the patients reached legal blindness (≥1.0 log MAR) based on visual acuity (64 years for both groups; log-rank, p = 0.3); the risk of developing advanced retinal degeneration (patch or atrophy) with age (multiple logistic regression, p = 0.8); or the frequency of cystoid macular edema (31% vs. 26%, Fisher’s exact test, p = 0.4). ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina. The results are important for counseling ADGRV1 patients, who represent the minor patient subgroup.     

Phospholipids and Alzheimer’s Disease: Alterations,Mechanisms and Potential Biomarkers

Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to different pathogenic processes in the brain, such as in Alzheimer’s disease (AD), the most common type of dementia among older populations. There is increasing evidence that phospholipid changes occur during pathogenic processes in AD. It is known that lipids are tightly connected with metabolism of the Amyloid Precursor Protein (APP), which produces Amyloid-beta peptide (Aβ), the main component of senile plaques, which represent the main pathological hallmark of AD. However, the mechanism(s) of the lipid-effect on Aβ metabolism and AD pathogenesis is still not completely understood. This review summarizes the current knowledge on phospholipid changes occurring during normal aging and discusses phospholipid changes in the human brain associated with different stages of AD, as well changes in the cerebrospinal fluid and blood/plasma, which are interesting potential biomarkers for AD diagnosis and disease monitoring. At the end, we have discussed future perspectives of phospholipid changes as potential biomarkers and as targets for development of novel treatment strategies against AD.     

An Overview,Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon-Like Peptide-1 Receptor

Due to uncomfortable injection regimens of peptidic agonists of glucagon-like peptide-1 receptor (GLP-1R), orally available nonpeptide positive allosteric modulators (PAMs) of GLP-1Rs are foreseen as the possible future mainstream therapy for type 2 diabetes. Herein, current GLP-1R PAMs are reviewed. Based on the effectiveness and in silico predicted physicochemical properties, pharmacokinetics, and toxicity, possible candidates for further development as oral drugs were selected. The suggestion is that GLP-1R PAMs might be used orally alone or in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors, which could offer an optimal treatment option next to metformin monotherapy in type 2 diabetes mellitus, or in a wider spectrum of indications. Quercetin acts as a GLP-1R PAM and DPP-4 inhibitor, and therefore, might be considered as a pioneering agent with a dual mechanism of action, in terms of GLP-1R positive allosteric modulation and DPP-4 inhibition for potentiating GLP-1 dependent effects.     

MALDI Q-TOF CID MS for Diagnostic Ion Screening of Human Milk Oligosaccharide Samples

Human milk oligosaccharides (HMO) represent the bioactive components of human milk, influencing the infant’s gastrointestinal microflora and immune system. Structurally, they represent a highly complex class of analyte, where the main core oligosaccharide structures are built from galactose and N-acetylglucosamine, linked by 1–3 or 1–4 glycosidic linkages and potentially modified with fucose and sialic acid residues. The core structures can be linear or branched. Additional structural complexity in samples can be induced by endogenous exoglycosidase activity or chemical procedures during the sample preparation. Here, we show that using matrix-assisted laser desorption/ionization (MALDI) quadrupole-time-of-flight (Q-TOF) collision-induced dissociation (CID) as a fast screening method, diagnostic structural information about single oligosaccharide components present in a complex mixture can be obtained. According to sequencing data on 14 out of 22 parent ions detected in a single high molecular weight oligosaccharide chromatographic fraction, 20 different oligosaccharide structure types, corresponding to over 30 isomeric oligosaccharide structures and over 100 possible HMO isomers when biosynthetic linkage variations were taken into account, were postulated. For MS/MS data analysis, we used the de novo sequencing approach using diagnostic ion analysis on reduced oligosaccharides by following known biosynthetic rules. Using this approach, de novo characterization has been achieved also for the structures, which could not have been predicted.     

Synthesis and characterization of crystalline hexagonal bipods of zinc oxide

The preparation of nano- and submicrometre-sized one-dimensional (1D) zinc oxides (ZnOs) from zinc nitrate was performed by precipitation with urea in two types of solvents (water and water/polyol mixtures). The influence of different polyols (ethylene glycol, diethylene glycol and tetraethylene glycol) on the size of the final particles (length and diameter) is presented for the first time. As well as the influence of the solvents used, the ratio of water/polyol, temperature, pH and time of synthesis was correlated with the size and morphology of the final particles. In all cases crystalline ZnO was synthesized in the form of hexagonal bipods. The morphological and crystalline properties of the samples obtained were characterized by SEM, IR, and XRD.     

Linking business and requirements engineering: is solution planning a missing activity in software product companies?

A strong link between strategy and product development is important, since companies need to select requirements for forthcoming releases. However, in practice, connecting requirements engineering (RE) and business planning is far from trivial. This paper describes the lessons learned from four software product companies that have recognized the need for more business-oriented long-term planning. The study was conducted using the action research approach. We identified five practices that seem to strengthen the link between business decisions and RE. These are (1) explicating the planning levels and time horizons; (2) separating the planning of products’ business goals from R&D resource allocation; (3) planning open-endedly with a pre-defined rhythm; (4) emphasizing whole-product thinking; and (5) making solution planning visible. To support whole-product thinking and solution planning, we suggest that companies create solution concepts. The purpose of the solution concept is to provide a big picture of the solution and guide RE activities.     

Influence of Whey Protein Addition and Feed Moisture Content on Chosen Physicochemical Properties of Directly Expanded Corn Extrudates

Production of extrudates from cereals is an often-used technological process in today’s world food industry. Extrudates from corn flour produced using the twin-screw extrusion process and enriched with whey protein concentrate represent high-quality source of proteins and fats. Whey protein concentrate (WPC) as a valuable source of proteins and minerals is one of the highest-quality components for possible extrudate enrichment. In this paper, the influence of various WPC addition and some extrusion process parameters such as feed moisture content ( Q_{\textH\text2 \textO} Q_{{{\text{H}}_{\text{2}} {\text{O}}}} ) on physicochemical properties of directly expanded corn flour extrudates manufactured in twin-screw co-rotating extruder was investigated. Whey protein concentrate was added in the following ratios 7.5%, 15% and 22.5% and water in 10.08, 12.18 and 14.28 L/h. Final composition of products is determined with measuring of protein, fat and water shares, water absorption index (WAI) and water solubility index (WSI). With added WPC and with increase of water volume flow, there was a significant rise in total protein, fat and water content in final products, as well as lowering of WSI and rising of WAI indexes. The statistical analysis of the obtained data shows that the lowest WSI and the highest WAI had samples with the largest share of WPC (22.5%) and water volume flow of 14.28 L/h. Colour is measured for each sample, and results were represented with hue angle (H), chroma (C) and lightness (L) values. Process parameters, WPC and Q_{\textH\text2 \textO} Q_{{{\text{H}}_{\text{2}} {\text{O}}}} influence the increase of saturation of C and lightness of L colour value, while H value stays unchanged. Mean value of H was 90.14 ± 1.06, which corresponds to dominance of yellow colour of samples.     

Setup and procedure for online identification of electricallystimulated muscle with Matlab Simulink

This paper first describes a laboratory setup for biomechanical experiments that runs within the universal simulation environment Matlab Simulink. The overall system comprises a personal computer, two AMTI (Advanced Mechanical Technology, Inc., Watertown, MA 02472) force plates, Parotec force-sensor shoe insoles, Optotrak system for noncontact 3D position measuring, and a computer-controlled four-channel electrical stimulator. Conceptually, the most important application is implementation of closed-loop electrical stimulation of intact and paralyzed subjects in the laboratory. Second, the system was tested in real-time muscle model identification procedure during a standing experiment. The plantarflexors of three nonimpaired subjects were excited with pseudorandom binary sequences (PRBSs) with small deviations around selected operating points. Electrically stimulated muscles were presented with a linear local dynamic block that was identified with a recursive least-square method (RARX). RARX block was designed with fundamental Matlab Simulink blocks that support real-time operation. Introduced was online estimation of model output, which offers a great manner of instant model validation. Two modes of operation with online validation were tested, In the first mode, the operating point for selected excitation level was identified online. In the second mode, the operating point was measured in preceding experiments. Both procedures resulted in satisfying second-order models that will be used in the adaptive controller design     

Structural Steel ASTM A709—Behavior at Uniaxial Tests Conducted at Lowered and Elevated Temperatures, Short-Time Creep Response, and Fracture Toughness Calculation

This paper presents the temperature dependence of the mechanical properties of structural high-strength low-alloy (HSLA) ASTM A709 Gr50 steel (En10025: S355 JO; DIN: ST 52-3U). Engineering stress-strain diagrams at lowered and elevated temperatures are presented. Creep responses for selected constant stresses at selected temperatures are also presented and are fit with a rheological model. Additionally, a relation between impact toughness and fracture toughness is proposed and is validated using results from notch impact tests on a Charpy pendulum impact machine.     

Semantic Mediation for Standard-Based B2B Interoperability

The authors discuss a semantic-mediation architecture to advance traditional approaches for standards-based business-to-business (B2B) interoperability. The architecture is supported by the Athena Knowledge Representation and Semantics Mediation tool suite. Initial experimentations with the architecture and the toolset offer discussions of key architectural and functional aspects and suggest directions for future tools enhancements.