СОЛОВЯНЕНКО Денис Владимирович

Recensie van: G.J. Johannes, De barometer van de smaak. Tijdschriften in Nederland 1770-1830. SDU Uitgevers Den Haag, 1995

Adhesion of RFL-treated cords to rubber : new insights into interfacial phenomena

Reinforcement of rubber by cords is crucial for many applications such as high-pressure hoses and conveyor belts. However, the largest application of cord-rubber composites is the tyre. The carcass of the tyre contains a network of cords that gives the tyre its strength. Not only the type of cord material that is used determines the performance, but also the way the cords are positioned in the carcass, as described in Chapter 1. Since the cords absorb most of the forces where the tyre is subjected to, a good adhesion between cord and rubber is an absolute requirement.\ud The coating which the cords need to obtain sufficient adhesion to rubber compounds is called the Resorcinol Formaldehyde Latex (RFL) treatment. Despite the importance of good adhesion and the fact that this RFL-treatment has been widely applied since the Second World War, and no better alternative has been found till today, the mechanism by which the adhesion is obtained has remained unclear. The relatively few publications on this technique are described in Chapter 2. Most of the research described was rather empirical: the many factors involved when dipping the cords in a RFL-dip and curing it to rubber were varied and their influence on the adhesion was described. However, most of the publications lack a mechanistic approach to obtain more fundamental knowledge about this technique.\ud With new fibre materials introduced in recent years, in particular aramid fibres, there is a renewed interest in the mechanism of adhesion of RFL-treated cords to rubber in order to utilise the properties of these high-performance fibres to their full extent in rubber compounds. In this thesis, an attempt is made to elucidate the adhesion between RFL-treated cords and rubber using a more systematic approach to obtain a mechanistic view on the chemical and physical processes involved

Lipophilic iminosugars : synthesis and evaluation as inhibitors of glucosylceramide metabolism

The study described in this thesis was conducted with the aim of developing lipophilic iminosugars as selective inhibitors for glucosylceramide synthase, glucocerbrosidase and _-glucosidase 2 that are enzymes involved in glucosylceramide metabolism. The study has resulted in many novel inhibitors of these three enzymes among which several that improve upon the inhibition profile of the lead compound in this study. The successful use of lipophilic iminosugars in type 2 diabetes models and the partial elucidation of their mechanism of action therein provide prospects for their development towards therapeutics for diabetes type 2.UBL - phd migration 201

Stimulation des EGF-Rezeptors in HNSCC-Zelllinien führt zu einer Hochregulation von Bcl-xL und zeigt Abhängigkeiten vom untersuchten Zelltyp

Bösartige Tumore zählen neben Herz-Kreislauf-Erkrankungen zu den häufigsten Todesursachen, wobei maligne Tumore des Kopf-Halsbereiches einen Anteil von ca. 6% ausmachen. Zu über 90% handelt es sich hierbei um Plattenepithelkarzinome (HNSCC, head and neck squamous cell carcinoma). In den vergangenen drei Jahrzehnten kam es trotz großer Fortschritte in der chirurgischen sowie der Radio(Chemo)therapie bei Patienten mit Kopf-Hals-Karzinomen zu einer nur geringen Steigerung der Fünf-Jahres-Überlebensrate. Eine Störung des physiologischen Apoptosemechanismus der maligne entarteten Zelle spielt eine zentrale Rolle bei der Progression der Tumorerkrankung sowie der Entwicklung von Therapieresistenzen, welche die Prognose des Patienten bestimmen. Aus diesem Grunde ist eine Analyse der zentralen Regulatoren der Apoptose, wie den Mitgliedern der Bcl-2 Protein-Familie von eminenter Bedeutung. Der EGF-Rezeptor (EGFR, HER1, ErbB1), eine Rezeptor-Tyrosinkinase, ist in bis zu 100% von HNSCC Tumoren überexprimiert und korreliert in hohem Maße mit der Prognose der Erkrankung. Aus diesem Grunde war es das Ziel der vorliegenden Arbeit, die Abhängigkeit der anti-apoptotischen Mitglieder der Bcl-2 Protein-Familie, Bcl-2 und Bcl-xL vom EGFR Aktivierungsstatus zu untersuchen. Mittels Western Blot Analyse und immunhistochemischen Methoden wurden der Expressionsstatus von Bcl-2 und Bcl-xL in HNSCC-Zelllinien und Tumorgeweben bestimmt. Weiterhin wurde mittels Western Blot Analyse die Abhängigkeit der Bcl-2 und der Bcl-xL-Expression vom EGFR Aktivierungszustand untersucht. Die Ergebnisse zeigten, dass die Proteinexpression von Bcl-2 nach EGFR Aktivierung nicht sichtbar verändert wurde. Im Gegensatz hierzu nahm die Bcl-xL-Expression in praktisch allen untersuchten Zelllinien nach EGF-Stimulation deutlich zu. Um den EGFR abhängigen Effekt auf die Bcl-xL Expression bei HNSCC Tumorzellen näher zu definieren, wurde die Expression von Bcl-xL nach Titration des EGF-abhängigen Effektes mit 0,1; 1; 10; 100 und 1000 ng/ml EGF bestimmt. Hierbei zeigten sich bei den untersuchten Zelllinien unterschiedlich starke Änderungen der Bcl-xL Expression in Abhängigkeit von der EGFR Aktivierung. Diese zwischen den einzelnen Zelllinien beobachtete, variable Hochregulation von Bcl-xL deutet ebenfalls auf mögliche Unterschiede im Grad der EGFR-abhängigen Bcl-xL Expression zwischen verschiedenen HNSCC Tumoren in vivo hin. Dies könnte, zumindest teilweise, die häufig beobachtete, bei verschiedenen Patienten oft unterschiedlich stark ausgeprägte Apoptoseresistenz bei Kopf-Hals Tumoren erklären. Eine Quantifizierung der Bcl-xL mRNA mittels qRT-PCR, zeigte keine signifikante Erhöhung der Bcl-xL Transkripte in Abhängigkeit vom EGFR Aktivierungstatus. Da sich die Anzahl der Bcl-xL-Transkripte nach Stimulation mit EGF nicht sichtbar veränderte, erscheint weder die Erhöhung der Transkription, noch ein verminderter Abbau der vorhandenen mRNA bzw. eine verlängerte Halbwertzeit der Transkripte eine wahrscheinliche Ursache für die erhöhte Bcl-xL-Expression zu sein. Es ist daher zu vermuten, dass dieser Effekt am ehesten auf eine Verringerung des Proteinabbaus zurückzuführen ist. Dieses genauer aufzuklären ist ein Ziel weiterführender Untersuchungen. Zusammenfassend kann gesagt werden, dass die Bcl-xL-Expression in HNSCC Tumoren eine deutliche Abhängigkeit vom EGFR-Aktivierungsstatus aufweist, wobei die Aktivierung des Rezeptors am ehesten zu einer Verlängerung der biologischen Halbwertzeit des Proteins führt. Die Durchbrechung einer solchen EGFR-abhängigen Therapieresistenz aufgrund einer Hochregulation von Bcl-xL unterstützt gegenwärtige Therapiekonzepte bei der Behandlung von Kopf-Halskarzinomen, welche eine Hemmung des EGF-Rezeptors zum Ziel haben. Der Einsatz von EGFR Hemmern, wie zum Beispiel monoklonalen gegen die EGFR-Ligandenbindungsstelle gerichteten Antikörpern oder Hemmstoffen der intrazellulären Kinasedomäne des Rezeptors erscheint vor diesem Hintergrund von großer Bedeutung bei der Therapie von Kopf-Hals-Karzinomen

The Neutral-Niche Debate:A Philosophical Perspective

Ecological communities around the world are under threat while a consensus theory of community structure remains elusive. In the last decade ecologists have struggled with two seemingly opposing theories: niche-based theory that explains diversity with species’ differences and the neutral theory of biodiversity that claims that much of the diversity we observe can be explained without explicitly invoking species’ differences. Although ecologists are increasingly attempting to reconcile these two theories, there is still much resistance against the neutral theory of biodiversity. Here we argue that the dispute between the two theories is a classic example of the dichotomy between philosophical perspectives, realism and instrumentalism. Realism is associated with specific, small-scale and detailed explanations, whereas instrumentalism is linked to general, large-scale, but less precise accounts. Recognizing this will help ecologists get both niche-based and neutral theories in perspective as useful tools for understanding biodiversity patterns

Перевірка суб’єктів господарювання державного сектора економіки: ревізія чи аудит?

The house sparrow (Passer domesticus) is an important model species in ecology and evolution. However, until recently, genomic resources for molecular ecological projects have been lacking in this species. Here, we present transcriptome sequencing data (RNA-Seq) from three different house sparrow tissues (spleen, blood and bursa). These tissues were specifically chosen to obtain a diverse representation of expressed genes and to maximize the yield of immune-related gene functions. After de novo assembly, 15250 contigs were identified, representing sequence data from a total of 8756 known avian genes (as inferred from the closely related zebra finch). The transcriptome assembly contain sequence data from nine manually annotated MHC genes, including an almost complete MHC class I coding sequence. There were 407, 303 and 68 genes overexpressed in spleen, blood and bursa, respectively. Gene ontology terms related to ribosomal function were associated with overexpression in spleen and oxygen transport functions with overexpression in blood. In addition to the transcript sequences, we provide 327 gene-linked microsatellites (SSRs) with sufficient flanking sequences for primer design, and 3177 single-nucleotide polymorphisms (SNPs) within genes, that can be used in follow-up molecular ecology studies of this ecological well-studied species

How improving access times had unforeseen consequences:a case study in a Dutch hospital

Objectives To investigate the consequences of increasing capacity to reduce access times, and to explore how patient waiting times and use of physical capacity were influenced by variability. Design A retrospective case study that combines both primary and secondary data. Secondary data were retrieved from a hospital database to establish inflow and outflow of patients, utilisation of resources and available capacity, realised access times and the weekly number of new patients seen over 1 year. Primary data consisted of field notes, onsite visits and observations, and semistructured interviews. Setting A secondary care facility, that is, a rheumatology department, in a large Dutch hospital. Participants Analyses are based on secondary patient data from the hospital database, and the responses of the interviews with physicians, nurses and Lean Six Sigma project leaders. Results The study shows that artificial variability was increased by managerial decisions to add capacity and to allow an increased inflow of new patients. This, in turn, resulted in undesirable and significant fluctuations in access times. We argue that we witnessed a new multiplier effect that typifies the fluctuations. Conclusions Adding capacity resources to reduce access times might appear an obvious and effective solution. However, the outcomes were less straightforward than expected, and even led to new artificial variability. The study reveals a phenomenon that is specific to service environments, and especially healthcare, and has detrimental consequences for access times

Direct imaging of glycans in Arabidopsis roots via click labeling of metabolically incorporated azido-monosaccharides

Background: Carbohydrates, also called glycans, play a crucial but not fully understood role in plant health and development. The non-template driven formation of glycans makes it impossible to image them in vivo with genetically encoded fluorescent tags and related molecular biology approaches. A solution to this problem is the use of tailor-made glycan analogs that are metabolically incorporated by the plant into its glycans. These metabolically incorporated probes can be visualized, but techniques documented so far use toxic copper-catalyzed labeling. To further expand our knowledge of plant glycobiology by direct imaging of its glycans via this method, there is need for novel click-compatible glycan analogs for plants that can be bioorthogonally labelled via copper-free techniques. Results: Arabidopsis seedlings were incubated with azido-containing monosaccharide analogs of N-acetylglucosamine, N-acetylgalactosamine, l-fucose, and l-arabinofuranose. These azido-monosaccharides were metabolically incorporated in plant cell wall glycans of Arabidopsis seedlings. Control experiments indicated active metabolic incorporation of the azido-monosaccharide analogs into glycans rather than through non-specific absorption of the glycan analogs onto the plant cell wall. Successful copper-free labeling reactions were performed, namely an inverse-electron demand Diels-Alder cycloaddition reaction using an incorporated N-acetylglucosamine analog, and a strain-promoted azide-alkyne click reaction. All evaluated azido-monosaccharide analogs were observed to be non-toxic at the used concentrations under normal growth conditions. Conclusions: Our results for the metabolic incorporation and fluorescent labeling of these azido-monosaccharide analogs expand the possibilities for studying plant glycans by direct imaging. Overall we successfully evaluated five azido-monosaccharide analogs for their ability to be metabolically incorporated in Arabidopsis roots and their imaging after fluorescent labeling. This expands the molecular toolbox for direct glycan imaging in plants, from three to eight glycan analogs, which enables more extensive future studies of spatiotemporal glycan dynamics in a wide variety of plant tissues and species. We also show, for the first time in metabolic labeling and imaging of plant glycans, the potential of two copper-free click chemistry methods that are bio-orthogonal and lead to more uniform labeling. These improved labeling methods can be generalized and extended to already existing and future click chemistry-enabled monosaccharide analogs in Arabidopsis

Sociale ondernemingen in Noord-Nederland: een verkenning:onderzoek naar belemmeringen en ondersteuningsbehoefte

In Noord-Nederland zijn sociale ondernemingen in opkomst, net als in de rest van Nederland. We hebben een eerste regionale verkenning van de aard en omvang van deze sector uitgevoerd. Hoe ziet de groep van sociale ondernemingen in deze regio er uit? Welke belemmeringen komen ze tegen en aan welke ondersteuning hebben ze behoefte