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The paper describes a concept for developing a dedicated combat asset for performing effective fragmentation attack on surface targets and having dimensions and weight suited to being carried by an unmanned aerial vehicle (UAV) with a maximum payload of 150 kg. The designed combat asset, i.e. cluster bomblets ejected from a reusable submunition dispenser, will be intended for destroying enemy personnel, unarmoured ground targets, lightly armoured equipment, ground support equipment, and aircraft and field ammunition depots. The introduction of the paper analyzed the existing submunition dispenser and cluster bomblet solutions. The key aspects of the paper include the calculation of the effective blast radius of the designed cluster bomblet and the analysis of the trajectory of a bomb dropped from horizontal flight. A bombing analysis was carried out, taking into account the influence of the atmosphere and drop control conditions on bombing accuracy and proper fragment coverage of the bombed area. A preliminary concept of the airdrop control system was developed, which could enable effective bombing with a series of cluster bomblets. As part of the work, element models and CAD assembly models of the dispenser and cluster bomblet structures were fabricated.

The work presents an application that enables the calculation of the basic geometric dimensions of parachutes used in the sounding rocket recovery systems. Determining the geometry of the parachute canopy, based on the equation of aerodynamic drag, which allows to obtain the object drop velocity declared by the user. The developed application also enables the visualization of the parachute canopy geometry selected according to the specific requirements of the mission. The key element of the work is the possibility of obtaining the geometry of a single segment of the parachute canopy along with the necessary allowance for the seam, which significantly facilitates the process of making a ready-to-use parachute. As part of this study, the results of the calculations made with the use of the application were verified on the basis of data collected during the flight of the experimental sounding rocket.

Using original cold-formed rivets in repairs of airframes of helicopters is difficult due to no access to inside parts of the airframe. Thus, the main aim of the study was to investigate the possibility to use the blind rivets or hybrid joints by verification the fatigue performance of such joints that must be better than with original rivets. Riveted and hybrid joints have been experimentally tested under static and fatigue loads. Furthermore, numerical calculations of stress distribution for strapped joint have been conducted. The test results covered fatigue life of lap joints and models of repaired airframe sheets using ordinary mushroom head rivets ref. 3558A-4-10, titanium driven blind bolts with pin, ref. MBF2110AB-05-150 and modified hybrid joints. Using titanium driven blind bolts with pin instead of ordinary hammer-bucked rivets, can improve the fatigue life of element made of aluminum alloy AW 2024T3. There are advantages of replacing riveted joints with modified hybrid (rivet & adhesive) joints in threefold increase in fatigue life of repaired airframe structures.

Article presents the simulation model and the study of the basic mechanisms of the GSh-23 aviation autocannon. The research made use of Solid Edge ST9 software and the multibody systems method implemented in it. Simulation of functioning cannon mechanisms was carried out for two variants of forcing a piston mechanism movement by the gunpowder gases. The results obtained are time courses of a bolt and a cartridge belt drive mechanism elements movement. Assumed variants of a piston mechanism movement and elaborated simulation model will be verified in the next (planned) stage of studies basing on the results of the measurements of the experimental kinematic parameters utilising high-speed camera (Phantom) and TEMA software.

Endothelial dysfunction is one of the hallmarks of vascular abnormalities in metabolic diseases and has been repeatedly demonstrated in coronary and peripheral circulation in mice fed high-fat diet (HFD), particularly after long-term HFD. However, the temporal relationship between development of coronary microvascular endothelial dysfunction and deterioration in diastolic and systolic cardiac function after short-term feeding with HFD has not yet been studied. This study aimed to correlate the changes in coronary microvascular endothelial function and global cardiac performance indices in vivo after short-term feeding with HFD in mice. Short-term feeding with a HFD (60% fat + 1% cholesterol) resulted in severely impaired coronary microvascular function, as evidenced by the diminished effect of nitric oxide synthase inhibition (by L-NAME) assessed using T

Background Extracellular nucleotide metabolism contributes to chronic inflammation, cell differentiation, and tissue mineralization by controlling nucleotide and adenosine concentrations and hence its purinergic effects. This study investigated location-specific changes of extracellular nucleotide metabolism in aortic valves of patients with calcific aortic valve disease (CAVD). Individual ecto-enzymes and adenosine receptors involved were analyzed together with correlation with CAVD severity and risk factors. Results Nucleotide and adenosine degradation rates were adversely modified on the aortic surface of stenotic valve as compared to ventricular side, including decreased ATP removal (1.25 ± 0.35 vs. 2.24 ± 0.61 nmol/min/cm2) and adenosine production (1.32 ± 0.12 vs. 2.49 ± 0.28 nmol/min/cm2) as well as increased adenosine deamination (1.28 ± 0.31 vs. 0.67 ± 0.11 nmol/min/cm2). The rates of nucleotide to adenosine conversions were lower, while adenosine deamination was higher on the aortic sides of stenotic vs. non-stenotic valve. There were no differences in extracellular nucleotide metabolism between aortic and ventricular sides of non-stenotic valves. Furthermore, nucleotide degradation rates, measured on aortic side in CAVD (n = 62), negatively correlated with echocardiographic and biochemical parameters of disease severity (aortic jet velocity vs. ATP hydrolysis: r = − 0.30, p

Vascular inflammation is an important factor in the pathophysiology of cardiovascular diseases, such as atherosclerosis. Changes in the extracellular nucleotide and in particular adenosine catabolism may alter a chronic inflammation and endothelial activation. This study aimed to evaluate the relation between vascular ecto-adenosine deaminase (eADA) activity and endothelial activation in humans and to analyze the effects of LPS-mediated inflammation on this activity as well as mechanisms of its increase. Moreover, we investigated a therapeutic potential of ADA inhibition by deoxycofromycin (dCF) for endothelial activation. We demonstrated a positive correlation of vascular eADA activity and ADA1 mRNA expression with endothelial activation parameters in humans with atherosclerosis. The activation of vascular eADA was also observed under LPS stimulation in vivo along with endothelial activation, an increase in markers of inflammation and alterations in the lipid profile of a rat model. Ex vivo and in vitro studies on human specimen demonstrated that at an early stage of vascular pathology, eADA activity originated from activated endothelial cells, while at later stages also from an inflammatory infiltrate. We proposed that LPS-stimulated increase in endothelial adenosine deaminase activity could be a result of IL-6/JAK/STAT pathway activation, since the lack of IL-6 in mice was associated with lower vascular and plasma eADA activities. Furthermore, the inhibitors of JAK/STAT pathway decreased LPS-stimulated adenosine deaminase activity in endothelial cells. We demonstrated that cell surface eADA activity could be additionally regulated by transcytosis pathways, as exocytosis inhibitors including lipid raft inhibitor, methyl-β-cyclodextrin decreased LPS-induced eADA activity. This suggests that cholesterol-dependent protein externalization mediated by lipid rafts could be an important factor in the eADA increase. Moreover, endocytosis inhibitors and exocytosis activators increased this activity on the cell surface. Furthermore, the inhibition of adenosine deaminase in endothelial cells in vitro attenuated LPS-mediated IL-6 release and soluble ICAM-1 and VCAM-1 concentration in the incubation medium through the restoration of the extracellular adenosine pool and adenosine receptor-dependent pathways. This study demonstrated that the vascular endothelial eADA activity remains under control of inflammatory mediators acting through JAK/STAT pathway that could be further modified by dyslipidemic-dependent exocytosis and transcytosis pathways. Inhibition of eADA blocked endothelial activation suggesting a crucial role of this enzyme in the control of vascular inflammation. This supports the concept of eADA targeted vascular protection therapy.

Military aviation does not serve solely for defending our own country's airspace; it is also use to ensure transport, evacuation, and rescue, also to perform protective tasks to the military as well as public and communications infrastructure of the country. The paper presents history of polish aircraft armament development. It consists the beginning of aviation in Poland and then development of polish military aviation armament during interwar and postwar period. Special attention is paid to recent developments of the polish technological know-how in this area. Authors emphasize contribution polish research and industrial centers in aircraft armament new design development, existing armament modernization as well as maintenance efficiency improvement of armament systems. Future of aircraft armament in Polish Armed Forces imply necessity of replacement of post Russian equipment by procurement of modern aircraft armament systems and development -implementation projects in order to achieve advance in polish aircraft weaponry.

Monocyte chemoattractant protein-induced protein 1 (MCPIP1, alias Regnase1) is a negative regulator of inflammation, acting through cleavage of transcripts coding for proinflammatory cytokines and by inhibition of NFκB activity. Moreover, it was demonstrated, that MCPIP1 regulates lipid metabolism both in adipose tissue and hepatocytes. In this study, we investigated the effects of tissue-specific Mcpip1 deletion on the regulation of hepatic metabolism and development of non-alcoholic fatty liver disease (NAFLD).We used knock-in control Mcpip1fl/fl mice and animals with deletion of Mcpip1 in myeloid leukocytes (Mcpip1fl/flLysMCre) and in hepatocytes (Mcpip1fl/flAlbCre), which were fed chow or a high-fat diet (HFD) for 12 weeks. Mcpip1fl/flLysMCre mice were fed a chow diet were characterized by a significantly reduced hepatic expression of genes regulating lipid and glucose metabolism, which subsequently resulted in hypoglycemia and dyslipidemia. These animals also displayed systemic inflammation, demonstrated by increased concentrations of cytokines in the plasma. On the other hand, there were no significant changes in phenotype in Mcpip1fl/flAlbCre mice. Although we detected a reduced hepatic expression of genes regulating glucose metabolism and β-oxidation in these mice, they remained asymptomatic. Upon feeding them a HFD, Mcpip1fl/flLysMCre mice did not develop obesity, glucose intolerance, nor hepatic steatosis, but were characterized by hypoglycemia and dyslipidemia, along with proinflammatory phenotype with symptoms of cachexia. Mcpip1fl/flAlbCre animals, following a HFD, became hypercholesterolemic, but accumulated lipids in the liver at the same level as Mcpip1fl/fl mice, and no changes in the level of soluble factors tested in the plasma were detected.In conclusion, we have demonstrated that Mcpip1 protein plays an important role in the liver homeostasis. Depletion of Mcpip1 in myeloid leukocytes, followed by systemic inflammation, has a more pronounced effect on controlling liver metabolism and homeostasis than the depletion of Mcpip1 in hepatocytes.

Arterial hypertension is one of the major health risk factors leading to coronary artery disease, stroke or peripheral artery disease. Dietary uptake of inorganic nitrite (NO2−) and nitrate (NO3−) via vegetables leads to enhanced vascular NO bioavailability and provides antihypertensive effects. The present study aims to understand the underlying vasoprotective effects of nutritional NO2− and NO3− co-therapy in mice with angiotensin-II (AT-II)-induced arterial hypertension. High-dose AT-II (1 mg/kg/d, 1w, s. c.) was used to induce arterial hypertension in male C57BL/6 mice. Additional inorganic nitrite (7.5 mg/kg/d, p. o.) or nitrate (150 mg/kg/d, p. o.) were administered via the drinking water. Blood pressure (tail-cuff method) and endothelial function (isometric tension) were determined. Oxidative stress and inflammation markers were quantified in aorta, heart, kidney and blood. Co-treatment with inorganic nitrite, but not with nitrate, normalized vascular function, oxidative stress markers and inflammatory pathways in AT-II treated mice. Of note, the highly beneficial effects of nitrite on all parameters and the less pronounced protection by nitrate, as seen by improvement of some parameters, were observed despite no significant increase in plasma nitrite levels by both therapies. Methemoglobin levels tended to be higher upon nitrite/nitrate treatment. Nutritional nitric oxide precursors represent a non-pharmacological treatment option for hypertension that could be applied to the general population (e.g. by eating certain vegetables). The more beneficial effects of inorganic nitrite may rely on superior NO bioactivation and stronger blood pressure lowering effects. Future large-scale clinical studies should investigate whether hypertension and cardiovascular outcome in general can be influenced by dietary inorganic nitrite therapy.

Background Long‐term feeding with a high‐fat diet (HFD) induces endothelial dysfunction in mice, but early HFD‐induced effects on endothelium have not been well characterized. Methods and Results Using an magnetic resonance imaging‐based methodology that allows characterization of endothelial function in vivo, we demonstrated that short‐term (2 weeks) feeding with a HFD to C57BL/6 mice or to E3L.CETP mice resulted in the impairment of acetylcholine‐induced response in the abdominal aorta (AA), whereas, in the thoracic aorta (TA), the acetylcholine‐induced response was largely preserved. Similarly, HFD resulted in arterial stiffness in the AA, but not in the TA. The difference in HFD‐induced response was ascribed to distinct characteristics of perivascular adipose tissue in the TA and AA, related to brown‐ and white‐like adipose tissue, respectively, as assessed by histology, immunohistochemistry, and Raman spectroscopy. In contrast, short‐term HFD‐induced endothelial dysfunction could not be linked to systemic insulin resistance, changes in plasma concentration of nitrite, or concentration of biomarkers of glycocalyx disruption (syndecan‐1 and endocan), endothelial inflammation (soluble form of vascular cell adhesion molecule 1, soluble form of intercellular adhesion molecule 1 and soluble form of E‐selectin), endothelial permeability (soluble form of fms‐like tyrosine kinase 1 and angiopoietin 2), and hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1). Conclusions Short‐term feeding with a HFD induces endothelial dysfunction in the AA but not in the TA, which could be ascribed to a differential response of perivascular adipose tissue to a HFD in the AA versus TA. Importantly, early endothelial dysfunction in the AA is not linked to elevation of classical systemic biomarkers of endothelial dysfunction.

Background & AimsPrimary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1, alias Regnase1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC.MethodsGenetic deletion of Zc3h12a was used to characterize the role of Mcpip1 in the pathogenesis of PBC. 6-52-week-old Mcpip1fl/fl and Mcpip1AlbKO mice were used for immunohistochemical, biochemical and molecular tests.ResultsWe found that Mcpip1 deficiency in the liver recapitulates most of the features of human PBC, in contrast to mice with Mcpip1 deficiency in myeloid cells (Mcpip1LysMKO mice), which present with robust myeloid cell-driven systemic inflammation. In Mcpip1AlbKO livers, intrahepatic bile ducts displayed proliferative changes with inflammatory infiltration, bile duct destruction, and fibrosis leading to cholestasis. In plasma, increased concentrations of IgG, IgM, and AMA autoantibodies (anti-PDC-E2) were detected. Interestingly, the phenotype of Mcpip1AlbKO mice was robust in 6-week-old and 52-week-old mice, but milder in 12-24-week-old mice, suggesting early prenatal origin of the phenotype and age-dependent progression of the disease. Hepatic transcriptome analysis of 6-week-old and 24-week-old Mcpip1AlbKO mice showed 812 and 8 differentially expressed genes (DEGs), respectively, compared with age-matched control mice, and revealed a distinct set of genes compared to those previously associated with development of PBC.ConclusionsThe phenotype of Mcpip1AlbKO mice recapitulates most of the features of human PBC, and demonstrates early prenatal origin and age-dependent progression of PBC. Therefore, Mcpip1AlbKO mice provide a unique model for the study of PBC.Lay summaryDeletion of hepatic Mcpip1 in Mcpip1AlbKO mice leads to development of PBC that recapitulates phenotype of human patients. These animals, show early prenatal origin and age-dependent progression of the disease. Thus, Mcpip1AlbKO mice provide a unique model for studying PBC.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC. Genetic deletion of Zc3h12a was used to characterize the role of Mcpip1 in the pathogenesis of PBC in 6-52-week-old mice. We found that Mcpip1 deficiency in the liver (Mcpip1

Lungs, due to their high oxygen availability and vascularization, are an ideal environment for cancer cell migration, metastasis and tumour formation. These processes are directly connected with extracellular matrix (ECM) remodelling, resulting from cancer cell infiltration and preparation of the environment suitable for tumour growth. Herein, we compare the potential of fast, label-free and non-destructive methods of Fourier-transform infrared spectroscopy (FT-IR) in standard and high definition (HD) modes with nonlinear coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF) and a fluorescence lifetime imaging (FLIM) technique for lung metastasis detection. We show their potential in the detection of lung macrometastasis, in which we already observed the ECM remodelling. The CARS image revealed a dense cell fraction typical of ECM remodeling and reduction of the TPEF signal together with an increase of fluorescence lifetime predominantly due to NAD(P)H suggesting metabolic changes in the metastatic foci. FT-IR spectroscopy allowed not only for macrometastasis detection but also their stage definition based mainly on the analysis of proteins, RNA and glycogen fractions. The multimodal approach additionally suggested partial enzymatic degradation of elastin in ECM and collagen remodelling.

A new type of aggregates, formed in human red blood cells (RBCs) in response to glutaraldehyde treatment, were discovered and analyzed with the classical and advanced biomolecular imaging techniques. Advanced Heinz body-like aggregates (AHBA) formed in a single human RBC are characterized by higher level of hemoglobin (Hb) degradation compared to typical Heinz bodies, which are consist of hemichromes. The complete destruction of porphyrin structure of Hb and the aggregation of the degraded proteins with the presence of Fe3+ ions are observed. The presence of such aggregated, highly degraded proteins inside RBC, without cell membrane destruction, has been never reported before. For the first time the spatial differentiation of two kinds of protein mixtures inside the single RBC, with different phenylalanine (Phe) conformations, is visualized. The non-resonant Raman spectra of altered RBCs with AHBA are characterized by presence of a strong band located at 1037 cm-1, which confirms that glutaraldehyde interacts strongly with Phe. The shape-shifting of RBC from the biconcave disk to spherical structure as well as sinking of AHBA to the bottom of the cell are observed. Results reveal that presence of AHBA should be considered when fixing RBCs and indicate the analytical potential of Raman spectroscopy, atomic force microscopy and scanning near-filed optical microscopy in AHBA detection and analysis.

Praca stanowi kolejny etap rozwoju koncepcji lotniczo-rakietowego systemu wynoszenia niewielkich satelitów na niską orbitę okołoziemską przy wykorzystaniu samolotów MiG-29 oraz Su-22. W ramach tego etapu podjęto się zadania analizy możliwości zwiększenia udźwigu użytecznego tych samolotów. Stwierdzono, że cel ten można zrealizować, zmniejszając masę własną samolotu poprzez usunięcie elementów jego wyposażenia bojowego. Stąd też przeprowadzono analizę możliwości usunięcia elementów systemu sterowania bronią oraz współpracujących z nim urządzeń wykonawczych. Wykorzystując dokumentację techniczną rozważanych samolotów, dokonano szczegółowej analizy ww. systemów uzbrojenia w aspekcie ich demontażu, a wyniki prac zebrano w tabelach. W ramach pracy dokonano obliczeń wyważenia samolotu MiG-29 po usunięciu wybranych elementów. Do tego celu wykorzystano model masowy CAD samolotu opracowany w systemie NX. Obliczono, iż po demontażu zaproponowanej części wyposażenia bojowego samolotu MiG-29 środek masy całego obiektu misyjnego wędruje do 28% średniej cięciwy aerodynamicznej, co mieści się w dozwolonym przedziale (23,7%-30,5% MAC). W przypadku Su-22 stwierdzono, iż ponad 80% masy urządzeń wytypowanych do usunięcia leży w pobliżu środka masy samolotu, przez co ich usunięcie nie wpłynie znacząco na wyważenie samolotu.

An application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to healthy control (HC) and late phase of metastasis (advanced macrometastasis, AM) using murine model of metastatic breast cancer with 4T1 cells orthotopically inoculated. FTIR imaging allows for a detailed, objective and label-free differentiation and visualization of EM foci including large and small micrometastases as well as single cancer cells grouped in clusters. An effect of the EM phase on the entire lung tissue matrix as well as characteristic biochemical profiles for HC and advanced macrometastasis were determined from morphological and spectroscopic points of view. The extraordinary sensitivity of FTIR imaging toward EM detection and discrimination of AM borders confirms its applicability as a complementary tool for the histopathological assessment of the metastatic cancer progression.

// Marta Smeda 1 , Anna Kieronska 1 , Bartosz Proniewski 1 , Agnieszka Jasztal 1 , Anna Selmi 1 , Krystyna Wandzel 1 , Agnieszka Zakrzewska 1 , Tomasz Wojcik 1 , Kamil Przyborowski 1 , Katarzyna Derszniak 1 , Marta Stojak 1 , Dawid Kaczor 1 , Elzbieta Buczek 1 , Cezary Watala 2 , Joanna Wietrzyk 3 and Stefan Chlopicki 1, 4 1 Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland 2 Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Kosciuszki 4, Lodz 90-419, Poland 3 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Rudolfa Weigla 4, Wroclaw 53-114, Poland 4 Chair of Pharmacology, Jagiellonian University, Medical College, Grzegorzecka 16, Krakow 31-531, Poland Correspondence to: Stefan Chlopicki, email: stefan.chlopicki@jcet.eu Keywords: mouse breast cancer; vascular mimicry; platelet inhibition; aspirin; clopidogrel Received: November 01, 2017 Accepted: February 25, 2018 Published: April 03, 2018 ABSTRACT Platelet inhibition has been considered an effective strategy for combating cancer metastasis and compromising disease malignancy although recent clinical data provided evidence that long-term platelet inhibition might increase incidence of cancer deaths in initially cancer-free patients. In the present study we demonstrated that dual anti-platelet therapy based on aspirin and clopidogrel (ASA+Cl), a routine regiment in cardiovascular patients, when given to cancer-bearing mice injected orthotopically with 4T1 breast cancer cells, promoted progression of the disease and reduced mice survival in association with induction of vascular mimicry (VM) in primary tumour. In contrast, treatment with ASA+Cl or platelet depletion did reduce pulmonary metastasis in mice, if 4T1 cells were injected intravenously. In conclusion, distinct platelet-dependent mechanisms inhibited by ASA+Cl treatment promoted cancer malignancy and VM in the presence of primary tumour and afforded protection against pulmonary metastasis in the absence of primary tumour. In view of our data, long-term inhibition of platelet function by dual anti-platelet therapy (ASA+Cl) might pose a hazard when applied to a patient with undiagnosed and untreated malignant cancer prone to undergo VM.

In this paper the object of research was the rotor rim of axial fan manufactured by MULTWING with the designation 5ZL. Experimental tests of the fan with the above mentioned rotor rim were carried out with factory tip clearance of 5 mm. Next, the geometry of the rotor rim was mapped and numerical simulations were carried out, as a result of which, displacements of the tip of the rotor blade were determined. Based on the results of mechanical simulations and the Traupel formula the possibility was found to reduce the tip clearance to 1 mm. In the next step, numerical flow simulations were performed for both tip clearance values. Obtained results, in the form of basic characteristics of axial fan, were compared with experimental results.

Numerous cellular and extracellular components should be analyzed in sections of atherosclerotic plaques to assess atherosclerosis progression and vulnerability. Here, we combined orcein (O) staining for elastic fibers and martius scarlet blue (MSB) polychrome to visualize various morphological contents of plaque in brachiocephalic arteries (BCA) of apoE/LDLR−/− mice. Elastic fibers (including broken elastic laminae and ‘buried’ fibrous caps) were stained purple and they could be easily distinguished from collagen fibers (blue). Orcein allowed clear identification of even the finest elastic fibers. Erythrocytes were stained yellow and they could easily be discerned from mature fibrin (red). Old fibrin tends to acquire blue color. The method of OMSB staining is simple, takes less than 1 h to perform and can be adapted to automatic stainers. Most importantly, the color separation is good enough to allow digital automatic segmentation of specific components in tissue section and quantitative analysis of the plaque constituents. OMSB was used to compare atherosclerotic plaques in proximal and distal regions of BCA in apoE/LDLR−/− mice. In conclusion, OMSB staining represents a novel staining that could be routinely used for qualitative and quantitative microscopic assessments of formaldehyde-fixed and paraffin-embedded sections of arteries with atherosclerotic lesions.

Streszczenie Cel – Wdrozenie czynności doradczych audytu wewnetrznego w obszarze przygotowan Policji do zabezpieczenia Finalu Regat „The Tall Ships Races 2017”. Metodologia badania – Zastosowano metode mapy ryzyka w audycie wewnetrznym dla identyfikacji potrzeb i diagnozowania ryzyka na bazie zebranych danych od kadry kierowniczej oraz wyznaczonych do zabezpieczenia uczestnikow wydarzen specjalnych. Wynik – Na podstawie analizy przeprowadzonej z wykorzystaniem mapy ryzyka uzyskano informacje o potencjalnych rodzajach ryzyka i ich wplywie na organizacje zabezpieczenia imprezy masowej. Ponadto zaprezentowano kierunki rekomendacji czynności doradczych. Oryginalnośc/Wartośc – Material badawczy pozwolil na obiektywne i niezalezne zapoznanie sie z zagadnieniem oraz wyciągniecie merytorycznych wnioskow dotyczących wdrozenia czynności doradczych. Slowa kluczowe: audyt wewnetrzny, czynności doradcze, ryzyko, impreza masowa

The paper presents selected problems of fatigue life of bolt joints. An analysis of factors influencing fatigue life of bolt joints was performed and selected methods of improving life were described. Authors presents examples of numerical calculations with use of ANSYS software which depict influence of pre-tension in the bolt on fatigue life of the joint. Presented results of life calculation were carried out for bolt joint loaded along bolt axis and for bolt lap joint loaded perpendicular to bolt axis.

Precision and reliability are critical requirements in the aerospace field, relying on suitable measurement methods to assure their achievement. As a consequence, the role of aerospace metrology is becoming more widely recognized as a value-added component. The paper presents a brief overview of the research and testing activities performed at the advanced laboratories of the Military University of Technology in Warsaw dealing with the test of airplane subsystems.

The presented paper contains outline of the probabilistic method of the reliability and durability estimation of aircraft on-board accumulator batteries. Unrecognized precisely processes which lead to battery capacity changes, allow formulation of hypothesis concerning process of battery ageing. Analysis of empirical data permits formulation of function which describes battery capacity changes. It formed the basis for developing of probabilistic model of dynamics of capacity changes. After that, mathematical expression of battery durability distribution was determined. Authors describe the method of durability estimation for assumed probability of exceeding the acceptable value of battery capacity and estimation of durability distribution parameters. Presented considerations were substantiated by calculation example.

Tytuła Andrzej, Bartosik Katarzyna, Jasztal-Kniażuk Anita, Buczek Weronika, Błaszkiewicz Aleksandra, Borzęcka-Sapko Agnieszka. Analysis of the prevalence of pediculosis and scabies in orphanages and refugee shelters in south-eastern Poland. Journal of Education, Health and Sport. 2019;9(3):493-500. eISNN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.2605743 http://ojs.ukw.edu.pl/index.php/johs/article/view/6733 https://pbn.nauka.gov.pl/sedno-webapp/works/908703 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part b item 1223 (26/01/2017). 1223 Journal of Education, Health and Sport eissn 2391-8306 7 © The Authors 2019; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.03.2019. Revised: 15.03.2019. Accepted: 26.03.2019. Analysis of the prevalence of pediculosis and scabies in orphanages and refugee shelters in south-eastern Poland Andrzej Tytuła1, Katarzyna Bartosik2, Anita Jasztal-Kniażuk1, Weronika Buczek2, AleksandraBłaszkiewicz2, Agnieszka Borzęcka-Sapko2 1Regional Chamber of Nurses and Midwives in Lublin 2Medical University of Lublin, Chair and Department of Biology and Parasitology Abstract Grouping conditions refer to a situation when number of entities is considered as a unit. The members of such a community resides in a certain area at a specified time and has to comply with specific rules of social life. The analysis of the data from orphanages and refugee shelters in south-eastern Poland has confirmed that this type of living conditions promote transmission of scabies and pediculosis, and these diseases were most frequently diagnosed in young people taking active part in social life. Our study revealed that invasions of Pediculus humanus and Sarcoptes scabiei are still current public health threats although the obligation to report cases of these diseases in Poland has been abolished. Keywords: pediculosis capitis, scabies, orphanages, refugee shelters, Poland

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The endothelium plays an important role in cancer metastasis, but the mechanisms involved are still not clear. In the present work, we characterised the changes in endothelial function at early and late stages of breast cancer progression in an orthotopic model of murine mammary carcinoma (4T1 cells). Endothelial function was analysed based on simultaneous microflow liquid chromatography–tandem mass spectrometry using multiple reaction monitoring (microLC/MS-MRM) quantification of 12 endothelium-related biomarkers, including those reflecting glycocalyx disruption – syndecan-1 (SDC-1), endocan (ESM-1); endothelial inflammation – vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin (E-sel); endothelial permeability – fms-like tyrosine kinase 1 (FLT-1), angiopoietin 2 (Angpt-2); and haemostasis – von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), as well as those that are pathophysiologically linked to endothelial function – adrenomedullin (ADM) and adiponectin (ADN). The early phase of metastasis in mouse plasma was associated with glycocalyx disruption (increased SDC-1 and ESM-1), endothelial inflammation [increased soluble VCAM-1 (sVCAM-1)] and increased vascular permeability (Angpt-2). During the late phase of metastasis, additional alterations in haemostasis (increased PAI-1 and vWF), as well as a rise in ADM and substantial fall in ADN concentration, were observed. In conclusion, in a murine model of breast cancer metastasis, we identified glycocalyx disruption, endothelial inflammation and increased endothelial permeability as important events in early metastasis, while the late phase of metastasis was additionally characterised by alterations in haemostasis., Summary: A microLC/MS-MRM-based approach for simultaneous determination of endothelium-related biomarkers identified glycocalyx disruption, endothelial inflammation and increased endothelial permeability as important events in early pulmonary metastasis in a murine model of breast cancer metastasis.

The role of nitric oxide (NO) in tumour progression and metastasis is not clear, therefore the present work aimed to better characterise the effects of nitric oxide synthase (NOS) inhibition by L-N

Background The early detection of metastasis based on biomarkers in plasma may improve cancer prognosis and guide treatment. The aim of this work was to characterize alterations in metabolites of the arginine pathway, energy metabolism, and structural and signalling lipids in plasma in the early and late stages of murine breast cancer metastasis. Methods Mice were orthotopically inoculated with 4T1 metastatic breast cancer cells, and plasma was analysed along the pulmonary metastasis progression using LC-MS/MS-based targeted metabolomics and lipidomics. Results Based on primary tumour growth and pulmonary metastases, 1–2 weeks after 4T1 cancer cell inoculation was defined as an early metastatic stage, and 3–4 weeks after 4T1 cancer cell inoculation was defined as a late metastatic stage. Early metastasis was featured in plasma by a shift of L-arginine metabolism towards arginase (increased ornithine/arginine ratio) and polyamine synthesis (increased putrescine). Late metastasis was reflected in plasma by further progression of changes in the arginine pathway with an additional increase in asymmetric dimethylarginine plasma concentration, as well as by a profound energy metabolism reprogramming towards glycolysis, an accelerated pentose phosphate pathway and a concomitant decrease in tricarboxylic cycle rate (“Warburg effect”). The late but not the early phase of metastasis was also characterized by a different lipid profile pattern in plasma, including a decrease in total phosphatidylcholines, a decrease in diester-bound phospholipid fraction and an increase in lysophospholipids associated with an increase in total sphingomyelins. Conclusions The early phase of metastasis in murine 4T1 metastatic breast cancer was associated with plasma metabolome changes characteristic of arginase activation and polyamine synthesis. The late metastasis was reflected in plasma not only by the alterations in arginine pathways but also by a shift towards glycolysis and the pentose pathway, remodelling of structural lipids and activation of lipid signalling, all of which coincided with metastasis progression. Electronic supplementary material The online version of this article (10.1186/s13058-018-1075-y) contains supplementary material, which is available to authorized users.

Mutations in NBEAL2, the gene encoding the scaffolding protein Nbeal2, are causal of gray platelet syndrome (GPS), a rare recessive bleeding disorder characterized by platelets lacking α-granules and progressive marrow fibrosis. We present here the interactome of Nbeal2 with additional validation by reverse immunoprecipitation of Dock7, Sec16a, and Vac14 as interactors of Nbeal2. We show that GPS-causing mutations in its BEACH domain have profound and possible effects on the interaction with Dock7 and Vac14, respectively. Proximity ligation assays show that these 2 proteins are physically proximal to Nbeal2 in human megakaryocytes. In addition, we demonstrate that Nbeal2 is primarily localized in the cytoplasm and Dock7 on the membrane of or in α-granules. Interestingly, platelets from GPS cases and Nbeal2-/- mice are almost devoid of Dock7, resulting in a profound dysregulation of its signaling pathway, leading to defective actin polymerization, platelet activation, and shape change. This study shows for the first time proteins interacting with Nbeal2 and points to the dysregulation of the canonical signaling pathway of Dock7 as a possible cause of the aberrant formation of platelets in GPS cases and Nbeal2-deficient mice.

Diabetes increases the risk of pulmonary hypertension and is associated with alterations in pulmonary vascular function. Still, it is not clear whether alterations in the phenotype of pulmonary endothelium induced by diabetes are distinct, as compared to peripheral endothelium. In the present work, we characterized differences between diabetic complications in the lung and aorta in db/db mice with advanced diabetes. Male, 20-week-old db/db mice displayed increased HbA1c and glucose concentration compatible with advanced diabetes. Diabetic lungs had signs of mild fibrosis, and pulmonary endothelium displayed significantly ultrastructural changes. In the isolated, perfused lung from db/db mice, filtration coefficient (Kf,c) and contractile response to TXA2 analogue were enhanced, while endothelial NO-dependent modulation of pulmonary response to hypoxic ventilation and cumulative production of NO2− were impaired, with no changes in immunostaining for eNOS expression. In turn, 6-keto-PGF1α release from the isolated lung from db/db mice was increased, as well as immunostaining of thrombomodulin (CD141). In contrast to the lung, NO-dependent, acetylcholine-induced vasodilation, ionophore-stimulated NO2− generation, and production of 6-keto-PGF1α were all impaired in aortic rings from db/db mice. Although eNOS immunostaining was not changed, that of CD141 was clearly lowered. Interestingly, diabetes-induced nitration of proteins in aorta was higher than that in the lungs. In summary, diabetes induced marked ultrastructural changes in pulmonary endothelium that were associated with the increased permeability of pulmonary microcirculation, impaired NO-dependent vascular function, with compensatory increase in PGI2 production, and increased CD141 expression. In contrast, endothelial dysfunction in the aorta was featured by impaired NO-, PGI2-dependent function and diminished CD141 expression.

Table S1. Gradient elution program applied for UPLC-MS analysis for positive ionisation mode. Table S2. Gradient elution program applied for UPLC-MS analysis for negative ionisation mode. Table S3. LC-MS/MS parameters in positive and negative ESI mode for determination of metabolites in plasma. Table S4. LC-MS/MS parameters for determination of S1P in plasma. (DOCX 24â kb)

1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/LDLR(-/-) mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F1 α and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR(-/-) mice, an effect associated with an improvement in prostacyclin- and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA.

Kidney transplant (KTx) is the best method of renal insufficiency treatment. In dialyzed patients, mortality rises with the time on dialysis. There is a continuing shortage of organs for transplantation, hence a propensity to expand the donor pool with expanded-criteria donors, anti-hepatitis C virus-positive included. In the above case a transmission of hepatitis C virus (HCV) genotype to recipient is present. It has been proven that contamination with more than 1 HCV genotype did not worsen KTx outcomes. There are 2.6% anti-HCV(+) donors in Poland. Use is only possible in cases of anti-HCV(+) and anti-HCV RNA(+) recipients. METHODS Retrospective analysis covered 8675 deceased donors (1998-2012 Polish data from Poltransplant). The early (after 12 months) and late (after 60 months) graft and patient survival was assessed in KTx recipients, with documented recipient and donor data spanning at least 1 year after KTx. In comprehensive analysis, 7016 KTx recipients with known anti-HCV status were included according to anti-HCV profile of recipient and donor. The results are in absolute and percentage values and P < .05 assessed with χ2 test. RESULTS Twelve-month survival: recipient (R) (95%), graft (G) (89%), total; R (95% vs 89%, P < .001), G (88 vs 79, P < .001) in HCV(-) to HCV(+/-) vs HCV(+) to HCV(+); R (95 vs 94, P = .2), G (88 vs 83, P < .001), HCV(-) to HCV(-) vs HCV(-) to HCV(+); R (93 vs 95, P = .004), G (82 vs 89, P < .001) in HCV(+/-) to HCV(+) vs HCV(-) to HCV(-); R (95 vs 89, P < .001), G (88 vs 79, P < .001) in HCV(-) to HCV(-) vs HCV(+) vs HCV (+). Sixty-month survival: R (86%), G (75%), total; R (84 vs 88, P = .01), G (63 vs 71, P = .001) in HCV(+/-) to HCV(+) vs HCV(-) to HCV(-); R (88 vs 80, P = .003) in HCV(-) to HCV(-) vs HCV(+) to HCV(+). CONCLUSIONS The worst anti-HCV serological profile was HCV(+) to HCV(+), although transplanting HCV(+) to HCV(+) did not worsen outcomes in that group. Worse KTx outcomes of HCV(+) over HCV(-) donors can be attributed to HCV(+) status of the recipient.

In this work, we describe a methodology to visualize the biochemical markers of atherosclerotic plaque in cross sections of brachiocephalic arteries (BCA) taken from ApoE/LDLR(-/-) mice. The approach of the visualization of the same area of atherosclerotic plaque with the use of Raman, IR and AFM imaging enables the parallel characterisation of various features of atherosclerotic plaques. This support to the histochemical staining is utilized mainly in studies on mice models of atherosclerotic plaques, where micro and sub-micro resolutions are required. This work presents the methodology of the measurement and visualization of plaque features important for atherosclerosis development and plaques vulnerability analysis. Label-free imaging of cholesterol, cholesteryl esters, remodeled media, heme, internal elastic lamina, fibrous cap and calcification provides additional knowledge to previously presented quantitative measurements of average plaque features. AFM imaging enhanced the results obtained with the use of vibrational microspectroscopies with additional topographical information of the sample. To the best of our knowledge, this is the first work which demonstrates that co-localized measurement of atherosclerotic plaque with Raman, IR and AFM imaging provides a comprehensive insight into the biochemical markers of atherosclerotic plaques, and can be used as an integrated approach to assess vulnerability of the plaque.

The role of nitric oxide (•NO) in metastatic cancer progression has not been fully explained. In the present work we characterized the development of •NO deficiency in the lung and examined changes in •NO and prostacyclin (PGI2)-dependent endothelial function in the systemic conduit artery (aorta), in relation to the progression of 4T1 metastatic breast cancer injected orthotopically in Balb/c mice. Furthermore, orthotopic and intravenous models of 4T1 metastatic cancer in mice were used to study the differential effects of L-NAME-induced •NO deficiency on the primary tumor and the metastatic burden. •NO was assessed in isolated aorta and lungs using EPR spin-trapping and chemiluminescence, while NOx in blood were measured using either EPR, chemiluminescence or Griess reaction. Early pulmonary metastasis was correlated with lung inflammation. Pulmonary endothelial function and systemic •NO availability in 4T1 breast cancer-bearing mice were compromised prior to the development of pulmonary metastasis,preceding the onset of its phenotypic switch toward a mesenchymal phenotype (EndMT). Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI2 pathway. L-NAME-induced •NO-deficiency showed that •NO plays a major role in the primary tumor development, but it is not the key mediator responsible for the regulation of cancer cell extravasation to the lungs in our model, despite clear-cut •NO-deficiency in the lung, reflected by a fall in systemic •NO bioavailability, both occurring early in the pre-metastatic phase.

The liver plays a central role in lipid metabolism, and abnormal lipid accumulation in the liver is a key feature of Non-Alcoholic Fatty Liver Disease. In experimental studies, quantification of liver steatosis is commonly based on lipids staining or biochemical analysis. Here, we present a spectroscopic approach for quantitative analysis of the lipid content in the freeze-dried liver. The method is based on vibrational spectroscopy (Raman and infrared) measurements applied for Partial Least Squares (PLS) regression modeling. The obtained PLS models show a good correlation of the spectroscopic data with the reference histological evaluation of steatosis based on Oil Red O (ORO)-stained images of liver cross sections. Vibrational spectroscopy with PLS-based modeling described here represents a useful approach for the fast assessment of the liver steatosis in a small sample of freeze-dried liver tissue. In conclusion, our work demonstrates the easy-to-use method that can be applied in laboratory routine as a beneficial alternative to the established ORO staining.

Using high definition (HD) and ultra-high definition (UHD) of Fourier-transform infrared (FTIR) spectroscopic imaging, we characterized spectrally pulmonary metastases in a murine model of breast cancer comparing them with histopathological results (Hematoxylin and eosin [H&E] staining). This comparison showed excellent agreement between the methods in case of localization of metastases with size below 1 mm and revealed that label-free HD and UHD IR spectral histopathology distinguish the type of neoplastic cells. We primary focused on differentiation between metastatic foci in the pleural cavity from cancer cells present in lung parenchyma and inflamed cells present in extracellular matrix of lungs due to growing of advanced metastases. In addition, a combination of unsupervised clustering and IR imaging indicated the high sensitivity of FTIR spectroscopy to identify chemical features of small macrometastases located under the pleural cavity and during epithelial-mesenchymal transition. FTIR-based spectral histopathology was proved to detect not only phases of breast cancer metastasis to lungs but also to differentiate various origins of metastases seeded from breast cancer.