24 research outputs found

    Unsymmetrically-Substituted 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione Scaffold—A Useful Tool for Bioactive Molecules Design

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    Unsymmetrically N-substituted and N,N’-disubstituted 5,12-dihydrodibenzo [b,f][1,4]diazocine-6,11-diones were synthesized in the new protocol. The desired modifications of the dibenzodiazocine scaffold were introduced at the stages of proper selection of building blocks as well as post-cyclization modifications with alkylation or acylation agents, expanding the structural diversity and possible applications of synthesized molecules. The extension of developed method resulted in the synthesis of novel: tricyclic 5,10-dihydrobenzo[b]thieno[3,4-f][1,4]diazocine-4,11-dione scaffold and fused pentacyclic framework possessing two benzodiazocine rings within its structure. Additionally, the unprecedented rearrangement of 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-diones to 2-(2-aminophenyl)isoindoline-1,3-diones was observed under the basic conditions in the presence of sodium hydride for secondary dilactams. The structures of nine synthesized products have been established by single-crystal X-ray diffraction analysis. Detailed crystallographic analysis of the investigated tri- and pentacyclic systems has shed more light on their structural features. One cell line derived from non-cancerous cells (EUFA30—human fibroblasts) and three tumor cells (U87—human primary glioblastoma, HeLa—cervix adenocarcinoma, BICR18—laryngeal squamous cell carcinoma) were used to determine the cytotoxic effect of the newly synthesized compounds. Although these compounds showed a relatively weak cytotoxic effect, the framework obtained for 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione could serve as a convenient privilege structure for the design and development of novel bioactive molecules suitable for drug design, development and optimization programs

    Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity against Leukemias and Lymphomas of Novel, Tricyclic Vorinostat Analogues

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    Histone deacetylase (HDAC) inhibitors are a class of drugs used in the cancer treatment. Here, we developed a library of 19 analogues of Vorinostat, an HDAC inhibitor used in lymphomas treatment. In Vorinostat, we replaced the hydrophobic phenyl group with various tricyclic ‘caps’ possessing a central, eight-membered, heterocyclic ring, and investigated the HDAC activity and cytotoxic effect on the cancer and normal cell lines. We found that 3 out of the 19 compounds, based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin- 6(5H)-one, and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds, showed better HDACs inhibition than the referenced Vorinostat. In leukemic cell line MV4-11 and in the lymphoma cell line Daudi, three compounds showed lower IC50 values than Vorinostat. These compounds had higher activity and selectivity against MV4-11 and Daudi cell lines than reference Vorinostat. We also observed a strong correlation between HDACs inhibition and the cytotoxic effect. Cell lines derived from solid tumours: A549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) as well as reference BALB/3T3 (normal murine fibroblasts) were less susceptible to compounds tested. Developed derivatives show improved properties than Vorinostat, thus they could be considered as possible agents for leukemia and lymphoma treatment

    Introducing the INSIGNIA project: environmental monitoring of pesticide use through honey bees

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    INSIGNIA aims to design and test an innovative, non-invasive, scientifically proven citizen science environmental monitoring protocol for the detection of pesticides by honey bees. It is a 30-month pilot project initiated and financed by the EC (PP-1-1-2018; EC SANTE). The study is being carried out by a consortium of specialists in honey bees, apiculture, statistics, analytics, modelling, extension, social science and citizen science from twelve countries. Honey bee colonies are excellent bio-samplers of biological material such as nectar, pollen and plant pathogens, as well as non-biological material such as pesticides or airborne contamination. Honey bee colonies forage over a circle of 1 km radius, increasing to several km if required, depending on the availability and attractiveness of food. All material collected is accumulated in the hive.The honey bee colony can provide four main matrices for environmental monitoring: bees, honey, pollen and wax. Because of the non-destructive remit of the project, for pesticides, pollen is the focal matrix and used as trapped pollen and beebread in this study. Although beeswax can be used as a passive sampler for pesticides, this matrix is not being used in INSIGNIA because of its polarity dependent absorbance, which limits the required wide range of pesticides to be monitored. Alternatively, two innovative non-biological matrices are being tested: i) the “Beehold tube”, a tube lined with the generic absorbent polyethylene-glycol PEG, through which hive-entering bees are forced to pass, and ii) the “APIStrip” (Absorbing Pesticides In-hive Strips) with a specific pesticide absorbent which is hung between the bee combs.Beebread and pollen collected in pollen traps are being sampled every two weeks to be analysed for pesticide residues and to record foraging conditions. Trapped pollen provides snapshots of the foraging conditions and contaminants on a single day. During the active season, the majority of beebread is consumed within days, so beebread provides recent, random sampling results. The Beehold tube and the APIStrips are present throughout the 2-weeks sampling periods in the beehive, absorbing and accumulating the incoming contaminants. The four matrices i.e. trapped pollen, beebread, Beehold tubes and APIStrips will be analysed for the presence of pesticides. The botanical origin of trapped pollen, beebread and pollen in the Beehold tubes will also be determined with an innovative molecular technique. Data on pollen and pesticide presence will then be combined to obtain information on foraging conditions and pesticide use, together with evaluation of the CORINE database for land use and pesticide legislation to model the exposure risks to honey bees and wild bees. All monitoring steps from sampling through to analysis will be studied and rigorously tested in four countries in Year 1, and the best practices will then be ring-tested in nine countries in Year 2. Information about the course of the project, its results and publications will be available on the INSIGNIA website www.insignia-bee.eu and via social media: on Facebook (https://www.facebook.com/insigniabee.eu/); Instagram insignia_bee); and Twitter (insignia_bee). Although the analyses of pesticide residues and pollen identification will not be completed until December 2019, in my talk I will present preliminary results of the Year 1 sampling.info:eu-repo/semantics/publishedVersio

    Introducing the INSIGNIA project: Environmental monitoring of pesticides use through honey bees

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    INSIGNIA aims to design and test an innovative, non-invasive, scientifically proven citizen science environmental monitoring protocol for the detection of pesticides via honey bees. It is a pilot project initiated and financed by the European Commission (PP-1-1-2018; EC SANTE). The study is being carried out by a consortium of specialists in honey bees, apiculture, chemistry, molecular biology, statistics, analytics, modelling, extension, social science and citizen science from twelve countries. Honey bee colonies are excellent bio-samplers of biological material such as nectar, pollen and plant pathogens, as well as non-biological material such as pesticides or airborne contamination. Honey bee colonies forage over a circle of about 1 km radius, increasing to several km if required depending on the availability and attractiveness of food. All material collected is concentrated in the hive, and the honey bee colony can provide four main matrices for environmental monitoring: bees, honey, pollen and wax. For pesticides, pollen and wax are the focal matrices. Pollen collected in pollen traps will be sampled every two weeks to record foraging conditions. During the season, most of pollen is consumed within days, so beebread can provide recent, random sampling results. On the other hand wax acts as a passive sampler, building up an archive of pesticides that have entered the hive. Alternative in-hive passive samplers will be tested to replicate wax as a “pesticide-sponge”. Samples will be analysed for the presence of pesticides and the botanical origin of the pollen using an ITS2 DNA metabarcoding approach. Data on pollen and pesticides will be then be combined to obtain information on foraging conditions and pesticide use, together with evaluation of the CORINE database for land use and pesticide legislation to model the exposure risks to honey bees and wild bees. All monitoring steps from sampling through to analysis will be studied and tested in four countries in year 1, and the best practices will then be ring-tested in nine countries in year 2. Information about the course of the project and its results and publications will be available in the INSIGNIA website www.insignia-bee.eu.info:eu-repo/semantics/publishedVersio

    Spatial Learning and Action Planning in a Prefrontal Cortical Network Model

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    The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to spatial cognition. Complementing hippocampal place coding, prefrontal representations provide more abstract and hierarchically organized memories suitable for decision making. We model a prefrontal network mediating distributed information processing for spatial learning and action planning. Specific connectivity and synaptic adaptation principles shape the recurrent dynamics of the network arranged in cortical minicolumns. We show how the PFC columnar organization is suitable for learning sparse topological-metrical representations from redundant hippocampal inputs. The recurrent nature of the network supports multilevel spatial processing, allowing structural features of the environment to be encoded. An activation diffusion mechanism spreads the neural activity through the column population leading to trajectory planning. The model provides a functional framework for interpreting the activity of PFC neurons recorded during navigation tasks. We illustrate the link from single unit activity to behavioral responses. The results suggest plausible neural mechanisms subserving the cognitive “insight” capability originally attributed to rodents by Tolman & Honzik. Our time course analysis of neural responses shows how the interaction between hippocampus and PFC can yield the encoding of manifold information pertinent to spatial planning, including prospective coding and distance-to-goal correlates

    Output signal change analysis of an uncooled microbolometer focal plane array with respect to varying control voltages and operating point temperature

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    This paper presents results of output signal analysis of uncooled microbolometric focal plane array FPA. The analysis focuses on detectors manufactured by ULIS. The signal has been tested against varying control voltages, it is blind microbolometer biasing VSK and active microbolometer biasing VFID. The working point temperature of the environment was also altered in range from 5°C to 60°C. Such analysis can be used to check the results against current mathematical model of FPA’s behavior and verify validity of the measurement method in varying working conditions. Later it could allow explore possibility to design corrective algorithms

    A test stand for evaluation and calibration of thermal camera parameters

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    Kamery termowizyjne znajdują zastosowanie w coraz większej liczbie dziedzin nauki, techniki i życia. Wynikiem tego jest produkcja względnie niedrogich kamer termowizyjnych, które muszą zostać poddane kalibracji i ocenie zakładanych parametrów. W artykule zostało przedstawione zautomatyzowane stanowisko do pomiaru parametrów i kalibracji kamery termowizyjnej. Zostały opisane wszystkie elementy stanowiska takie jak moduł przemieszczeń liniowych i techniczne ciała doskonale czarne. Opisano również algorytmy i procedury wyznaczania parametrów i współczynników kalibracyjnych kamery termowizyjnej.Technological development in the field of infrared and thermal imaging has caused that thermal imaging cameras are used in more and more fields of science, technology and life. In the paper there is presented an automatic measurement and calibration stand capable of measuring the fundamental parameters of a thermal imaging camera. All components of the module, such as a linear motion controller and an actuator or a technical perfect black body are described. An algorithm for determining calibration parameters of the thermal imaging camera is presented. In the paper there are discussed the basic parameters of the calibrated infrared camera, the IR Capture device to capture data from the infrared camera via a specialized bus called the VideoBus. The UPCD and VideoBus standards are described. The paper presents the IRDiag software for recording the measurement data and determining the parameters and NUC correction factors used for infrared cameras. The software also allows control of all elements of the measurement stand and automation of most tasks performed by a user during the standard calibration procedure. The measurement stages are described and presented in the form of software window screenshots. The measurement stand was tested with regard to the accurate evaluation of parameters and calibration coefficients

    Thermal weapon sight - construction, parameters and test results

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    W artykule został przedstawiony celownik termowizyjny do broni strzeleckiej klasyfikowany, jako kamera III generacji. Celownik pracuje w zakresie dalekiej podczerwieni (LWIR) i zbudowany jest na bazie matrycowego mikrobolometrycznego detektora podczerwieni ze stabilizacją temperatury w układzie Peltiera. Celownik termowizyjny został zbadany laboratoryjnie (w tym badania klimatyczne i wibracyjne) i wyniki badań potwierdziły zakładane parametry taktyczno-techniczne. Celownik poddano także specjalistycznym badaniom poligonowym w Wojskowym Instytucie Technicznym Uzbrojenia, gdzie prowadzono badania strzelaniem na siedmiu typach broni od kalibru 5,56 mm do 12,7 mm.The paper presents the thermal weapon sight, which can be classified as 3-rd generation camera. The sight operates in the LWIR range and uses microbolometer focal plane array with thermoelectric temperature stabilizer. The sight has been thoroughly tested (including environmental and vibration tests) and the result confirmed its assumed technical and tactical characteristics. The sight was also tested at Military Institute of Armament Technology, where the shooting test were performed with different weapons of calibers ranging from 5.56 mm to 12.7 mm
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