Modification of structurally different polymers downstream of a microwave plasma

Since the mid 1960\u27s there have been numerous papers published on the modification of organic polymers in a pure oxygen or oxygen-f luorocarbon plasma. In terms of this thesis, chemical modification occurs when a polymer is either passivated (fluorinated) or etched. Many parameters influence the degree to which a polymer is modified downstream of a microwave (MW) plasma. Some of the parameters include: substrate temperature, MW power, gas feed composition, chamber pressure and total gas flow rate; the latter two determine the gas flow velocity. One of the more important parameters, in the case of polyimide (PI), which influences etching, is the [0]/[F] ratio. That is. the ratio between the atomic oxygen concentration and the atomic fluorine concentration. [1,2,3

Nowa ewangelizacja w Kościele

Evangelization was known over centuries and well know in the history. First sending off the apostles, has characteristics of the proclamation of the Good News. Several Church’s documents tried to define the process of evangelization and to give it a new meaning. The first document is the Decree ad gentes on the mission activity of the Church of the Second Vatican Council, in which we read, that Christ was sent “to reveal and to communicate the love of God to all men and nations”. The mission ad gentes is concerned about those who never heard about Christ. Post-synodal Magisterium of the Church more often indicates that every baptised person is called to proclaim the Good News. The new evangelization means proclamation of the salvation in new way, it means to go out to modern man with modern forms and means of communication. Yet the most effective is one’s personal experience.This article shows an outline, concepts and attempts to define new evangelization in the light of the available materials, with particular attention to the Church’s documents which treat new evangelization in different perspectives. Then taken into account are the recipients of the Good News.Ewangelizacja była znana na przestrzeni wieków. Pierwsze posyłanie uczniów ma znamiona głoszenia dobrej nowiny. Liczne dokumenty Kościoła usiłowały zdefiniować dzieło ewangelizacji i nadać mu nowe znaczenie. Pierwszym dokumentem jest dekret o działalności misyjnej Kościoła ad gentes Soboru Watykańskiego II, w którym czytamy, że Chrystus został posłany, „aby ukazywać miłość Bożą i zaszczepiać ją wszystkim ludziom i narodom”. Misja ad gentes ma na uwadze tych, którzy nie słyszeli o Chrystusie. Posoborowe nauczanie Kościoła coraz częściej wskazuje, że każdy ochrzczony jest wezwany do głoszenia dobrej nowiny. Nowa ewangelizacja to głoszenie orędzia zbawienia na nowe sposoby, to wychodzenie ku współczesnym z nowymi formami i środkami. Jednak najskuteczniejsze jest osobiste świadectwo.Niniejszy artykuł ukazuje zarys, pojęcia i próbę zdefiniowania nowej ewangelizacji na tle dostępnych opracowań, zwrócenie uwagi na dokumenty Kościoła, w których temat nowej ewangelizacji poruszany jest w sposób wieloaspektowy. Następnie wzięci są pod uwagę adresaci Dobrej Nowiny

Characterization of hepatic macrophages and evaluation of inflammatory response in heme oxygenase-1 deficient mice exposed to scAAV9 vectors

Adeno-associated viral (AAV) vectors are characterised by low immunogenicity, although humoral and cellular responses may be triggered upon infection. Following systemic administration high levels of vector particles accumulate within the liver. Kupffer cells (KCs) are liver resident macrophages and an important part of the liver innate immune system. Decreased functional activity of KCs can contribute to exaggerated inflammatory response upon antigen exposure. Heme oxygenase-1 (HO-1) deficiency is associated with considerably reduced numbers of KCs. In this study we aimed to investigate the inflammatory responses in liver and to characterise two populations of hepatic macrophages in adult wild type (WT) and HO-1 knockout (KO) mice following systemic administration of one or two doses (separated by 3 months) of self-complementary (sc)AAV9 vectors. At steady state, the livers of HO-1 KO mice contained significantly higher numbers of monocyte-derived macrophages (MDMs), but significantly less KCs than their WT littermates. Three days after re-administration of scAAV9 we observed increased mRNA level of monocyte chemoattractant protein-1 (Mcp-1) in the livers of both WT and HO-1 KO mice, but the protein level and the macrophage infiltration were not affected. Three days after the 1st and 3 days after the 2nd vector dose the numbers of AAV genomes in the liver were comparable between both genotypes indicating similar transduction efficiency, but the percentage of transgene-expressing MDMs and KCs was higher in WT than in HO-1 KO mice. In the primary culture, KCs were able to internalize AAV9 particles without induction of TLR9-mediated immune responses, but no transgene expression was observed. In conclusion, in vivo and in vitro cultured KCs have different susceptibility to scAAV9 vectors. Regardless of the presence or absence of HO-1 and initial numbers of KCs in the liver, scAAV9 exhibits a low potential to stimulate inflammatory response at the analysed time points

Casein kinase 2 activity is a host restriction factor for AAV transduction

So far, the mechanisms that impede AAV transduction, especially in the human heart, are poorly understood, hampering the introduction of new, effective gene therapy strategies. Therefore, the aim of this study was to identify and overcome the main cellular barriers to successful transduction in the heart, using iPSC-derived cardiomyocytes (iPSC-CMs), cardiac fibroblasts (iPSC-CFs), and primary endothelial cells (HAECs) to model vector-host interactions. Through phosphoproteome analysis we established that casein kinase 2 (CK2) signalling is one of the most significantly affected pathways upon AAV exposure. Transient inhibition of CK2 activity substantially enhanced the transduction rate of AAV2, AAV6 and AAV9 in all tested cell types. In particular, CK2 inhibition improved the trafficking of AAVs through the cytoplasm, impaired DNA-damage response through destabilisation of Mre11 and altered the RNA processing pathways, which were also highly responsive to AAV transduction. Also, it augmented transgene expression in already transduced iPSC-CFs, which retain AAV genomes in a functional, but probably silent form. In summary, presented study provides new insights into the current understanding of the host-AAV vector interaction, identifying CK2 activity as a key barrier to efficient transduction and transgene expression, what may translate to improvement the outcome of AAV-based therapies in the future

Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin

Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here

TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells

BACKGROUND AND AIMS Tumour necrosis factor α (TNF-α) represents a classical proinflammatory cytokine and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti- TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. METHODS AND RESULTS Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCR-M) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence but the susceptible animals developed extensive inflammation in the heart. In the TCR-M model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. CONCLUSIONS TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches

Analysis of the nature of injuries in victims of fall from height

Aim of study: To assess the types and extent of injuries sustained by victims of fall from height depending on the height of fall. Material and methods: The study included 338 bodies of victims of fatal falls from different heights (from the 1st to 10th floors) who were subjected to medico-legal autopsy at the Department of Forensic Medicine, Jagiellonian University Medical College, between 1995 and 2014. For each individual, selected data were collected including gender, age, body height, injury types and presence of alcohol or other intoxicants in blood. The analysis comprised injuries to the brain, thoracic and abdominal organs, fractures of the skull, extremities, ribs and spine, and fractures of the scapula, clavicle and sternum (considered together). The study focused on determining the frequency of occurrence of different injuries in relation to one another and depending on the height of fall. Results : The number and extent of injuries was found to increase along with the height of fall. Three injury types, including injuries to the mesentery and both kidneys and fractures of upper extremity small bones, were shown to occur from the threshold heights of the 3rd, 4th and 6th floors. Eleven injuries demonstrated a statistically significant correlation with the height of fall. The study also revealed a number of correlations between the frequencies of occurrence of different injuries. Conclusions : Injuries found from the threshold value may suggest the minimal height of fall. The presence of injuries which correlate with increasing height, and the overall number of injuries observed in victims of fall from height, may be useful for inferring the height of the fall