RNAi in clinical studies

RNA interference (RNAi) is an efficient process of posttranscriptional gene silencing. In recent years it has been developed into a new technology in biopharmaceutical fields of science. RNAi products include short interference RNA (siRNA) but also short hairpin RNA (shRNA), bifunctional short hairpin RNA (bi-shRNA) and microRNA (miRNA). They combine with homologous fragments of the mRNA and cause its degradation. It results in inhibition of protein synthesis, or in mutation in the gene encoding it. RNAi has been used in analysis of genomes and creation of new animal models to test drugs. From the pharmaceutical point of view, what is the most important is its therapeutic application. So far the basic and clinical research has been focused on the following targets: macular degeneration, cancer and antiviral therapy. But there are also reports on clinical trials in asthma, hypercholesterolemia and genetic diseases such as inherited skin disorders and amyloidosis. Among over 20 therapeutics that reached clinical trials, only few are still investigated. Another few are clinical candidates. The review focuses on RNAi products under clinical evaluation and their most promising new applications

The impact of desirability and feasibility considerations for self and others

Construal Level Theory (CLT) proposes that social distance will operate similarly to temporal distance in that individuals' perceptions of others will be high level, abstract construals, and individuals' own perceptions will be low level, concrete construals (at least for the near future; Liberman, Trope, and Stephan in press, Trope and Liberman 2003). Consequently individuals will predict that desirability considerations are more important to others than to self, and will indicate that feasibility considerations are more important to self than to others. Four studies show this effect by examining the prediction of others' preferences, and the choices people make on behalf of others. These studies replicate the effect using different manipulations of desirability considerations (i.e., importance of brands in general, a specific brand of a consumer product, and attributes of a consumer product and experience) as well as feasibility considerations (i.e., importance of value in general, the price of a consumer product, and attributes of a consumer product and experience). Therefore, the effect is not driven solely by individuals' perceptions that they are more price sensitive than others, but rather results from perceived differences between self and others in the importance of the tradeoff between desirability and feasibility considerations. Results also indicate that closeness of the relationship to the other to the self is a moderator of the effect such that the effect is attenuated as the relationship to the other becomes closer to the self (i.e., average other vs. friend). Because individuals perceive that others value desirability considerations, results show that they report different preferences (i.e., preferences favoring desirability considerations) for themselves in public than they do in private. Consequently, the self-other difference not only influences the choices individuals make for others, but also the choices they make for themselves in different social settings. Two final studies examine representation of the other (i.e., level of concrete representation) as the underlying mechanism for the self-other effect. No conclusive evidence is found that a concrete representation attenuates the self-other effect. Future directions and managerial implications are discussed

Assessment of microplastics in the sediments around Hywind Scotland Offshore Wind Farm.

Leading edge erosion of turbine blades is hypothesized to be a source of microplastic (MP; 1-5000 µm) emissions from offshore wind farms (OWFs) to the marine environment. Given the higher density of rotor blade coating and leading-edge protection (LEP) materials than seawater, released MP are expected to enter the surrounding waters and sink to the sediments, where the highest concentrations may be expected in the sediments in and around the OWF infrastructure. Here, we present a methodological approach for the quantification and characterisation of coating and LEP MPs (>300 µm) in sediments, applied to samples collected from 15 locations around the Hywind Scotland floating OWF. To validate the approach, reference materials were produced from the different coating layers and LEP material and used to generate library IR spectra and mass spectra so that such particles could be robustly identified if present in the sediment samples. The reference materials were also used to evaluate particle integrity and recovery across the sample preparation applied to real samples (ZnCl2 density separation, filtration). Results suggested the LEP material was unaffected by the sample processing, but fragmentation was observed for the two coating layers studied, leading to an increase in the number of particles and a decrease in weight due to loss of particles <300 µm. After isolation, particles were evaluated using microscopy and suspected MP particles were identified and subjected to a detailed chemical characterisation by Fourier transform infrared spectroscopy (FTIR). In the field samples, twenty particles were confirmed as MP, but none had polymer compositions matching the coatings and LEP materials, instead representing common thermoplastics in the form of flakes, films, fragments, and filaments.publishedVersio

Monoclonal antibodies in targeted therapy

Terapia celowana jest nową metodą terapeutyczną polegającą na hamowaniu określonych szlaków molekularnych. Główną rolę w nowoczesnej terapii odgrywają przeciwciała monoklonalne, zaliczane do grupy leków biologicznych. Warunkiem powodzenia leczenia ukierunkowanego molekularnie jest zdefiniowanie właściwego „celu molekularnego”, dobranie odpowiedniego leku aktywnego wobec określonego „celu” oraz wyselekcjonowanie grupy chorych, która odnosi korzyści z leczenia. Wprowadzenie do terapii leków ukierunkowanych na cele molekularne przyczyniło się do poprawy wyników leczenia wielu ciężkich i przewlekłych schorzeń. Chociaż swoiste dla nich działania niepożądane są uważane za mniej nasilone i lepiej tolerowane niż indukowane przez standardową terapię, są przyczyną innych niepożądanych objawów, także mogących czasami zagrażać życiu pacjenta. Odpowiedni dobór chorych i monitorowanie leczenia znacząco zmniejsza ryzyko wystąpienia niebezpiecznych dla życia powikłań. Jednak nadal bardzo niewiele wiemy o odległych powikłaniach leczenia molekularnego. W USA i Europie zarejestrowano około 31 terapeutycznych przeciwciał monoklonalnych, 160 dopuszczono do badań klinicznych. W pracy przedstawiono terapeutyczne przeciwciała monoklonalne stosowane obecnie w terapii.Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper “molecular target”, selecting the right drug active against a specific “target” and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Patient selection and proper monitoring significantly decrease the risk of life-threatening adverse events. Data concerning late side effects are still unavailable because of the short follow-up of molecularly targeted therapy. Currently in the U.S. and Europe there are approximately 31 registered therapeutic monoclonal antibodies, while 160 are subjected to clinical trials. This paper presents an overview of therapeutic monoclonal antibodies currently used in therapy and the present state of knowledge about them

Automated measurement method for assessing thermal-dependent electronic characteristics of thin boron-doped diamond-graphene nanowall structures

This paper investigates the electrical properties of boron-doped diamond-graphene (B:DG) nanostructures, focusing on their semiconductor characteristics. These nanostructures are synthesized on fused silica glass and Si wafer substrates to compare their behaviour on different surfaces. A specialized measurement system, incorporating Python-automated code, was developed for an in-depth analysis of electronic properties under various contact configurations. This approach allowed for a detailed exploration of charge transport mechanisms within the nanostructures. The research highlights a decrease in resistivity with increased deposition time, as shown by Arrhenius plot analysis. This trend is linked to the formation and evolution of multi-wall graphene structures. SEM images showed nanowall structures formed more readily on amorphous fused silica substrates, enabling unrestricted growth. TOF-SIMS analysis revealed uneven boron atom distribution through the film depth. A significant finding is a reduction in conductive activation energy in samples grown in microwave plasma from 197 meV to 87 meV as deposition time increased from 5 to 25 min. Furthermore, the study identifies a shift in transport mechanisms from variable range hopping (VRH) below 170 K to thermally activated (TA) conduction above 200 K. These insights advance our understanding of the electronic behaviours in B:DG nanostructures and underscore their potential in electronic device engineering, opening new paths for future research and technological developments.publishedVersio

Spatial and Temporal Changes of Tidal Inlet Using Object-Based Image Analysis of Multibeam Echosounder Measurements: A Case from the Lagoon of Venice, Italy

Scientific exploration of seabed substrata has significantly progressed in the last few years. Hydroacoustic methods of seafloor investigation, including multibeam echosounder measurements, allow us to map large areas of the seabed with unprecedented precision. Through time-series of hydroacoustic measurements, it was possible to determine areas with distinct characteristics in the inlets of the Lagoon of Venice, Italy. Their temporal variability was investigated. Monitoring the changes was particularly relevant, considering the presence at the channel inlets of mobile barriers of the Experimental Electromechanical Module (MoSE) project installed to protect the historical city of Venice from flooding. The detection of temporal and spatial changes was performed by comparing seafloor maps created using object-based image analysis and supervised classifiers. The analysis included extraction of 25 multibeam echosounder bathymetry and backscatter features. Their importance was estimated using an objective approach with two feature selection methods. Moreover, the study investigated how the accuracy of classification could be affected by the scale of object-based segmentation. The application of the classification method at the proper scale allowed us to observe habitat changes in the tidal inlet of the Venice Lagoon, showing that the sediment substrates located in the Chioggia inlet were subjected to very dynamic changes. In general, during the study period, the area was enriched in mixed and muddy sediments and was depleted in sandy deposits. This study presents a unique methodological approach to predictive seabed sediment composition mapping and change detection in a very shallow marine environment. A consistent, repeatable, logical site-specific workflow was designed, whose main assumptions could be applied to other seabed mapping case studies in both shallow and deep marine environments, all over the world