Assessment of immunogenicity of romiplostim in clinical studies with ITP subjects

Romiplostim is an Fc-peptide fusion protein that activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor leading to increased platelet production. Romiplostim has been engineered to have no amino acid sequence homology to endogenous TPO. Recombinant protein therapeutics can be at a risk of development of an antibody response that can impact efficacy and safety. Hence, a strategy to detect potential antibody formation to the drug and to related endogenous molecules can be useful. The immunogenicity assessment strategy involved both the detection and characterization of binding and neutralizing antibodies. The method for detection was based on a surface plasmon resonance biosensor platform using the Biacore 3000. Samples that tested positive for binding antibodies in the Biacore immunoassay were then tested in a neutralization assay. Serum samples from 225 subjects with immune thrombocytopenic purpura (ITP) dosed with romiplostim and 45 ITP subjects dosed with placebo were tested for romiplostim and TPO antibodies. Prior to romiplostim treatment, 17 subjects (7%) tested romiplostim antibody positive and 12 subjects (5%) tested TPO antibody positive for pre-existing binding antibodies. After romiplostim exposure, 11% of the subjects exhibited binding antibodies against romiplostim and 5% of the subjects with ITP showed binding antibodies against TPO. The antibodies against romiplostim did not cross-react with TPO and vice versa. No cases of anti-TPO neutralizing antibodies were detected in romiplostim-treated subjects. The incidence of anti-romiplostim neutralizing antibodies to romiplostim was 0.4% (one subject); this subject tested negative at the time of follow-up 4 months later. No impact on platelet profiles were apparent in subjects that had antibodies to romiplostim to date. In summary, administration of romiplostim in ITP subjects resulted in the development of a binding antibody response against romiplostim and TPO ligand. One subject developed a neutralizing antibody response to romiplostim that impacted the platelet counts of this subject. No neutralizing antibodies to endogenous TPO were observed

Consideration of the bioavailability of metal/metalloid species in freshwaters: experiences regarding the implementation of biotic ligand model-based approaches in risk assessment frameworks

After the scientific development of Biotic Ligand Models (BLMs) in recent decades these models are now considered suitable for implementation in regulatory risk assessment of metals in freshwater bodies. The approach has been developed over several years and has been described in many peer-reviewed publications. The original complex BLMs have been applied in prospective risk assessment reports for metals and metal compounds and are also recommended as suitable concepts for the evaluation of monitoring data in the context of the European Water Framework Directive. Currently, several user-friendly BLM-based bioavailability software tools are available for assessing the aquatic toxicity of a limited number of metals (mainly copper, nickel, and zinc). These tools need only a basic set of water parameters as input (e.g., pH, hardness, dissolved organic matter and dissolved metal concentration). Such tools seem appropriate to foster the implementation in routine water quality assessments. This work aims to review the existing bioavailability-based regulatory approaches and the application of available BLM-based bioavailability tools for this purpose. Advantages and possible drawbacks of these tools (e.g., feasibility, boundaries of validity) are discussed, and recommendations for further implementation are given

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Modern diagnostic devices aiding the industrial oven condition monitoring

O żywotności i osiąganej zdolności produkcyjnej pieców przemysłowych decyduje ich stan techniczno-technologiczny. Mając powyższe na względzie Instytut Chemicznej Przeróbki Węgla od wielu lat prowadzi specjalistyczne oceny pieców, w tym głównie pieców koksowniczych. Dla usprawnienia i ujednolicenia tych ocen, w ramach realizowanego projektu badawczego „Inteligentna Koksownia spełniająca wymagania najlepszej dostępnej techniki”, wypracowano w Instytucie „Zintegrowany komputerowy system monitorowania stanu technicznego baterii koksowniczych”. Choć system ten bazuje głównie na wynikach wizualnych przeglądów stanu ceramiki i parametrach technologicznych odnotowywanych on-line w systemie bieżącej kontroli eksploatacji baterii, to jednak coraz częściej jego uzupełnieniem stają się ostatnio specjalistyczne analizy obrazów termowizyjnych i endoskopowych.The condition of and technology used in the industrial oven determine its life and production capacity. With that in mind, for many years the Institute for Chemical Processing of Coal in Zabrze (Instytut Chemicznej Przeróbki Węgla) has been carrying out specialised evaluations of industrial ovens, focusing predominantly on coke ovens. To improve and standardise the evaluations, an “Integrated computer system for coke battery condition monitoring” was produced as part of an ongoing research project “An Intelligent Coke Oven compliant with the requirements of the best modern technologies”.The system processes predominantly visual surveys of the condition of ceramic materials as well as technical parameters submitted online to a continuous battery monitoring system. However, it has been more and more frequently complemented by specialised analyses of thermal imaging data and endoscopic inspections

Advantages of use of the fused silica in coke oven battery brickwork repairs

Zakłady koksownicze planując renowację obmurza komór koksowniczych zwracają szczególną uwagę na czas trwania remontu, wynikające stąd zaburzenia eksploatacyjne a co za tym idzie straty produkcji koksu. Technologia klasycznego remontu masywu ceramicznego polegająca na odbudowie całości ścian lub ich fragmentów, bazuje od lat na wykorzystaniu standardowych kształtek krzemionkowych a ich rozszerzalność cieplna jest niezmiernie ważnym czynnikiem wpływającym na czas trwania remontu. Istotnym innowacyjnym rozwiązaniem w zakresie prowadzenia remontów gorących jak również remontów zimnych było zastosowanie tzw. kształtek o zerowej rozszerzalności (z krzemionki amorficznej). Jak wynika ze światowych doświadczeń zastosowanie tego typu materiału wpływa korzystnie na rezultat prowadzonych remontów zarówno w aspekcie technicznym, ekologicznym jak i ekonomicznym.During repairs planning, the coke plants, points out special care on the production disturbances and production losses connected with coke oven battery brickwork renovation. The classic repairs techniques are based on the traditional silica bricks, which thermal expansion is a large factor for time of the repair. The very innovative step was to use during hot and cold repairs the fused silica, which has zero thermal expansion. As shows the wide world experiences, the use of the fused silica contributes in a very good technical, ecological and economical results of the repairs

Fracture toughness of old bridge steel

Tematyka artykułu jest związana z zagadnieniami odporności na pękanie starej stali mostowej, która została pobrana z mostu kolejowego o okresie eksploatacji przekraczającym 100 lat. Omówiono podstawowe zagadnienia mechaniki pękania, a także podano szczegółowe informacje na temat procedur wyznaczania odporności na pękanie, które są stosowane w badaniach stali mostowych. Omówiono wyniki przeprowadzonych badań, w których oszacowano wartość całki JQ, określając tym samym odporności na pękanie badanej stali.The subject of paper is related to problems the of fracture toughness of old steel bridge which was taken from the railway bridge, that was loaded during more than 100 years. The basic problems of fracture mechanics, as well as detailed information on the procedures of determination of material fracture toughness, which were used in the steel bridge research, are presented. The results of the study, the critical values of JQ integral, defining the fracture toughness of investigated steel are discussed

Seasonal expression of insulin-like growth factor 1 (IGF-1), its receptor IGF-1R and klotho in testis and epididymis of the European bison (Bison bonasus, Linnaeus 1758)

The European bisons are the largest mammals of Europe that are still in danger of extinction. The species conservation is associated with their continuous reproduction, and bisons are characterized by the well-pronounced seasonality of reproductive processes. However, the exact mechanisms regulating their reproduction still remain unknown. Our previous studies indicated the involvement of some of the growth factors in the regulation of male seasonal reproductive activities in bison, showing expression patterns that seemed to be regulated by the length of the daylight. In the present study, using RT-PCR and Western blot approaches, we verified the expression and possible relationship between the insulin-like growth factor (IGF-1), its receptor (IGF-1R), and klotho in testis and epididymis of the European bison in pre- and post-reproductive periods, i.e., in June and in December. The observed expression of IGF-1 and IGF-1R mRNA in testis and epididymis was higher in June than in December. At the same time, klotho mRNA expression in both testis and epididymis did not differ between the analyzed seasons. However, along with the higher levels of IGF-1R protein observed in June, klotho protein levels for the membrane form and for the secrete form were higher in December than in June. Finally, the messenger and protein expression profiles presented herein indicate the importance of both the IGF-system and klotho in reproductive processes in the European bison, implying their involvement in the regulation of seasonal testicular activity in males of this threatened species