Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.     

Free and bound phenolic compounds in leaves of pak choi (Brassica campestris L. ssp. chinensis var. communis) and Chinese leaf mustard (Brassica juncea Coss)

Eleven pak choi cultivars and two leaf mustard cultivars grown under field conditions in China were investigated for the free polyphenol content in their outer and inner leaves, as well as in their leaf blades and leaf stalks. In most cases, there were no significant differences between the hydroxycinnamic acid derivative and flavonoid derivative contents in the outer and inner leaves for the 13 cultivars. However, the contents of blades and stalks differed: hydroxycinnamic acids and flavonoids were present in greater amounts in the leaf blade than in the leaf stalk. Trace or small amounts of flavonoids were detected in the pak choi and leaf mustard stalks. Additionally, the bound phenolic contents of two pak choi cultivars and two leaf mustard cultivars were investigated. The concentrations of cell wall-bound phenolic compounds were higher in the leaf blade than in the leaf stalk under field conditions in China. These compounds represent only a minor portion of the total phenolic contents (flavonoids and hydroxycinnamic acids) in leaf stalks (0.81–1.18%) and leaf blades (0.05–0.08%) from fresh plant material. The storage of plant samples from four Chinese cabbage cultivars resulted, in most cases, in an increase of phenolic content, within six days, at 4 °C and 20 °C. The increase might have been triggered by post-harvest plant stresses, which stimulate the biosynthesis of polyphenols.     

Intelligent download and cache management for interactive non-linear video

Since the invention of digital video significant progress has been made in reducing the amount of data needed to be transferred in the World Wide Web while improving viewing experience. However the paradigm of linear behavior has not changed at all. While the feature set of traditional digital video may be sufficient for some applications, there are several use cases where a significantly improved way of interacting with the content is highly desirable. It is possible to organize a video in an interactive and non-linear way. Additional information (for example high resolution images) can be added to any scene of the video. The non-linearity of the video flow and the implementation of additional content not found in traditional videos may lead to an increased download volume and/or a playback with many breaks for downloading missing elements. This paper describes a player framework for interactive non-linear videos. We developed the framework and its associated algorithms to simulate the playback of non-linear video content. It minimizes interruption when the sequence of scenes is directly influenced by interaction, while the traditional viewing experience is not altered. The evaluation showed that it is possible to reach shorter startup times using our strategies than using the strategies of other players. Furthermore, we demonstrated that a prefetching of elements does not lead to an increased download volume in every case. In contrast, it can even decrease the download volume if the right delete strategy is selected. It can be noted that the knowledge of the structure of interactive non-linear videos can be used to minimize startup times at the beginning of scenes while the download volume is not increased.     

Herstellung und Charakterisierung von zellstrukturiertem Apfelmaterial mit unterschiedlichem Pectingehalt

Zusammenfassung Ausgehend von Apfelparenchymgewebe wurden alkoholunlösliche Substanzen als hellfarbige Materialien mit cellularer Struktur und unterschiedlichem Pectingehalt hergestellt. Die Materialien haben unabhängig vom Pectingehalt vergleichbare funktionelle Eigenschaften und besitzen ein hohes Wasserbindevermögen über 50 g/g. Jedoch wird das Wasserbindevermögen bei den pectinarmen Materialien durch den Schritt der Pectinextraktion herabgesetzt. Die Herstellung des zellstrukturierten Materials mit niedrigem Pectingehalt kann über den Schritt einer einstufigen sauren Pectinextraktion mit der Isolierung von hochverestertem, hochmolekularem Pectin verknüpft werden. Beim Autoklavieren von rehydratisierten zellstrukturierten Materialien werden beträchtliche Mengen an wasserlöslichem, hoch verestertem, niedermolekularem Pectin freigesetzt. Das Autoklavieren und nachfolgende Aufbewahren der Proben bei Raumtemperatur führt zu sinkenden Werten der Helligkeit und der Fließgrenze.

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Preparation and characterization of materials with a cellular structure and different pectin contents from apple

Alcohol-insoluble substances in the form of light (colourless) materials with a cellular structure and two different pectin contents have been prepared from apple parenchyma. Except for the water-binding capacity, the pectin content was found to have only a small effect on the functional properties of the materials. The water-binding capacity of the materials was decreased by a step of pectin extraction. However, in all cases the water-binding capacity was higher than 50 g/g. It was found that the depectinization of the materials with a cellular structure by acid one-step pectin extraction can be combined with the isolation of a highly methoxylated, high-molecular-mass pectin. Considerable amounts of water-soluble, highly methoxylated but low-molecular-mass pectins are released from rehydrated materials with a cellular structure when subjected to autoclave treatment. Both autoclaving and storage at room temperature decrease the lightness and the flow limit value of the rehydrated materials.

     

Nanoliter Scale Parallel Liquid–Liquid Extraction for High-Throughput Purification on a Droplet Microarray

In the current drug discovery process, the synthesis of compound libraries is separated from biological screenings both conceptually and technologically. One of the reasons is that parallel on-chip high-throughput purification of synthesized compounds is still a major challenge. Here, on-chip miniaturized high-throughput liquid–liquid extraction in volumes down to 150 nL with efficiency comparable to or better than large-scale extraction utilizing separation funnels is demonstrated. The method is based on automated and programmable merging of arrays of aqueous nanoliter droplets with organic droplets. Multi-step extraction performed simultaneously or with changing conditions as well as handling of femtomoles of compounds are demonstrated. In addition, the extraction efficiency is analyzed with a fast optical readout as well as matrix-assisted laser desorption ionization-mass spectrometry on-chip detection. The new massively parallel and miniaturized purification method adds another important tool to the chemBIOS concept combining chemical combinatorial synthesis with biological screenings on the same miniaturized droplet microarray platform, which will be essential to accelerate drug discovery.     

State space analysis of Petri nets with relation-algebraic methods

A large variety of systems can be modelled by Petri nets. Their formal semantics are based on linear algebra which in particular allows the calculation of a Petri net’s state space. Since state space explosion is still a serious problem, efficiently calculating, representing, and analysing the state space is mandatory. We propose a formal semantics of Petri nets based on executable relation-algebraic specifications. Thereupon, we suggest how to calculate the markings reachable from a given one simultaneously. We provide an efficient representation of reachability graphs and show in a correct-by-construction approach how to efficiently analyse their properties. Therewith we cover two aspects: modelling and model checking systems by means of one and the same logic-based approach. On a practical side, we explore the power and limits of relation-algebraic concepts for concurrent system analysis.     

Progress Report on Phase Separation in Polymer Solutions

Polymeric porous media (PPM) are widely used as advanced materials, such as sound dampening foams, lithium‐ion batteries, stretchable sensors, and biofilters. The functionality, reliability, and durability of these materials have a strong dependence on the microstructural patterns of PPM. One underlying mechanism for the formation of porosity in PPM is phase separation, which engenders polymer‐rich and polymer‐poor (pore) phases. Herein, the phase separation in polymer solutions is discussed from two different aspects: diffusion and hydrodynamic effects. For phase separation governed by diffusion, two novel morphological transitions are reviewed: “cluster‐to‐percolation” and “percolation‐to‐droplets,” which are attributed to an effect that the polymer‐rich and the solvent‐rich phases reach the equilibrium states asynchronously. In the case dictated by hydrodynamics, a deterministic nature for the microstructural evolution during phase separation is scrutinized. The deterministic nature is caused by an interfacial‐tension‐gradient (solutal Marangoni force), which can lead to directional movement of droplets as well as hydrodynamic instabilities during phase separation.     

Resource Buying Games

In resource buying games a set of players jointly buys a subset of a finite resource set \(E\) (e.g., machines, edges, or nodes in a digraph). The cost of a resource \(e\) depends on the number (or load) of players using \(e\) , and has to be paid completely by the players before it becomes available. Each player \(i\) needs at least one set of a predefined family \({\mathcal S}_i\subseteq 2^E\) to be available. Thus, resource buying games can be seen as a variant of congestion games in which the load-dependent costs of the resources can be shared arbitrarily among the players. A strategy of player \(i\) in resource buying games is a tuple consisting of one of \(i\) ’s desired configurations \(S_i\in {\mathcal S}_i\) together with a payment vector \(p_i\in {\mathbb R}^E_+\) indicating how much \(i\) is willing to contribute towards the purchase of the chosen resources. In this paper, we study the existence and computational complexity of pure Nash equilibria (PNE, for short) of resource buying games. In contrast to classical congestion games for which equilibria are guaranteed to exist, the existence of equilibria in resource buying games strongly depends on the underlying structure of the families \({\mathcal S}_i\) and the behavior of the cost functions. We show that for marginally non-increasing cost functions, matroids are exactly the right structure to consider, and that resource buying games with marginally non-decreasing cost functions always admit a PNE.     

Deciphering Specificity Determinants for FR900359‐Derived Gqα Inhibitors Based on Computational and Structure–Activity Studies

Direct targeting of intracellular Gα subunits of G protein‐coupled receptors by chemical tools is a challenging task in current pharmacological studies and in the development of novel therapeutic approaches. In this study we analyzed novel FR900359‐based analogs from natural sources, synthetic cyclic peptides, as well as all so‐far known G_qα inhibitors in a comprehensive study to devise a strategy for the elucidation of characteristics that determine interactions with and inhibition of G_q in the specific FR/YM‐binding pocket. Using 2D NMR spectroscopy and molecular docking we identified unique features in the macrocyclic structures responsible for binding to the target protein correlating with inhibitory activity. While all novel compounds were devoid of effects on G_i and G_s proteins, no inhibitor surpassed the biological activity of FR. This raises the question of whether depsipeptides such as FR already represent valuable chemical tools for specific inhibition of G_q and, at the same time, are suitable natural lead structures for the development of novel compounds to target Gα subunits other than G_q.