Reconstruction of large cranial defects with poly-methyl-methacrylate (PMMA) using a rapid prototyping model and a new technique for intraoperative implant modeling

Background Reconstruction of large cranial defects after craniectomy can be accomplished by free-hand poly-methyl-methacrylate (PMMA) or industrially manufactured implants. The free-hand technique often does not achieve satisfactory cosmetic results but is inexpensive. In an attempt to combine the accuracy of specifically manufactured implants with low cost of PMMA. Methods Forty-six consecutive patients with large skull defects after trauma or infection were retrospectively analyzed. The defects were reconstructed using computer-aided design/computer-aided manufacturing (CAD/CAM) techniques. The computer file was imported into a rapid prototyping (RP) machine to produce an acrylonitrile-butadiene-styrene model (ABS) of the patient's bony head. The gas-sterilized model was used as a template for the intraoperative modeling of the PMMA cranioplasty. Thus, not the PMMA implant was generated by CAD/CAM technique but the model of the patients head to easily form a well-fitting implant. Cosmetic outcome was rated on a six-tiered scale by the patients after a minimum follow-up of three months. Results The mean size of the defect was 74.36cm2. The implants fitted well in all patients. Seven patients had a postoperative complication and underwent reoperation. Mean follow-up period was 41 months (range 2–91 months). Results were excellent in 42, good in three and not satisfactory in one patient. Costs per implant were approximately 550 Euros. Conclusion PMMA implants fabricated in-house by direct molding using a bio-model of the patients bony head are easily produced, fit properly and are inexpensive compared to cranial implants fabricated with other RP or milling techniques

Viral Mimicry Response Is Associated With Clinical Outcome in Pleural Mesothelioma

Introduction The aim of this study was to investigate endogenous retrovirus (ERV) expression and type I interferon (IFN) activation in human pleural mesothelioma (PM) and their association with clinical outcome. Methods The expression of ERV was determined from PM cohorts and mesothelial precursor RNA sequencing data. The expression of ERV was confirmed by quantitative polymerase chain reaction (qPCR). Methylation of genomic DNA was assessed by quantitative methylation-specific PCR. DNA demethylation was induced in cells by demethylating agent 5-Aza-2’-deoxycytidine (5-Aza-CdR) treatment. To block type I IFN signaling, the cells were treated with ruxolitinib or MAVS silencing. The expression of IFN-stimulated genes (ISGs) was determined by qPCR and Western blot. Circulating ERVs were detected by qPCR. Results Long terminal repeats (LTRs) represent the most abundant transposable elements up-regulated in PM. Within the LTR, ERVmap_1248 and LTR7Y, which are specifically enriched in PM, were further analyzed. The 5-Aza-CdR treatment increased the levels of ERVmap_1248 expression and induced ERVmap_1248 promoter demethylation in mesothelial cells. In addition, ERVmap_1248 promoter was more demethylated in the mesothelioma tissue compared with nontumor tissue. The 5-Aza-CdR treatment of the mesothelial cells also increased the levels of ISGs. Basal ISG expression was higher in the mesothelioma cells compared with the mesothelial cells, and it was significantly decreased by ruxolitinib treatment or MAVS silencing. Furthermore, ISG expression was higher in the tumor tissue with high expression levels of ERVmap_1248. High expression of ERVmap_1248 was associated with longer overall survival and BAP1 mutations. ERVmap_1248 and LTR7Y can be detected in the PM plasma. Conclusions We provide clues for patient stratification especially for immunotherapy where best clinical responses are associated with an activated basal immune response

Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment

We previously observed increased levels of adenosine-deaminase-acting-on-dsRNA (Adar)-dependent RNA editing during mesothelioma development in mice exposed to asbestos. The aim of this study was to characterize and assess the role of ADAR-dependent RNA editing in mesothelioma. We found that tumors and mesothelioma primary cultures have higher ADAR-mediated RNA editing compared to mesothelial cells. Unsupervised clustering of editing in different genomic regions revealed heterogeneity between tumor samples as well as mesothelioma primary cultures. ADAR2 expression levels are higher in BRCA1-associated protein 1 wild-type tumors, with corresponding changes in RNA editing in transcripts and 3'UTR. ADAR2 knockdown and rescue models indicated a role in cell proliferation, altered cell cycle, increased sensitivity to antifolate treatment, and type-1 interferon signaling upregulation, leading to changes in the microenvironment in vivo. Our data indicate that RNA editing contributes to mesothelioma heterogeneity and highlights an important role of ADAR2 not only in growth regulation in mesothelioma but also in chemotherapy response, in addition to regulating inflammatory response downstream of sensing nucleic acid structures

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Realizace distanční výuky v prostředí venkovské ZŠ

This final work deals with the topic of the implementation of distance education in a rural primary school. The theoretical part defines the monitored type of schools and describes in detail the development of regulations issued by the Ministry of Education since March 2020, when schools switched to distance education due to the COVID-19 pandemic. The practical part is based on the method of questionnaire survey and describes the implementation of distance education in primary school in Rapsach and 28 other schools of the same type in two periods - until June 2020 and from September 2020, when compulsory distance education was included in the legislative framework

Transport-Geographical Attributes of the South Bohemian Region

The diploma thesis deals with the analysis of the transport-geographical attributes of the South Bohemian Region. Basically, the thesis considers two important characteristics of the settlement structure-transport relationship. These are transport regionalization and hierarchization of the transport centres. Besides the viewpoint of the public transport the diploma thesis also deals with the individual automobile transport. The first chapters describe goals of the thesis and analyse relevant literature. These are followed by detailed methodological part containing the description of the choice of the settlement centres, delimitation of the transport regions and the analysis of hierarchy of the transport nodes. The further chapters analyse the real condition of the South Bohemian Region itself from the points of view of the attributes mentioned above

Utilising a high pressure, cross flow, stainless steel fintube heat exchanger for direct steam generation from recovered waste heat

Thesis (MScEng) -- Stellenbosch University, 2004.ENGLISH ABSTRACT: Around the world the implementation of heat recovery systems is playing an increasingly important role in the engineering inqustry. The recovered energy is utilised in the plants and saves companies millions in expenses per year. Not only is this seen on the grand scale of industry, but also in everyday life, where for instance turbochargers are used to boost the performance of automobiles by utilising the wasted energy expelled along with exhaust gasses. The aim of this project is to investigate a small scale waste heat recovery system, and to determine the optimum method by which to convert the recovered energy into electrical energy, which can be used as a secondary energy source. The research contained in this thesis, centres on the main components and theory needed for the construction of a small scale waste heat recovery system. Also included, is a theoretical analysis concerning the design and construction of the system, utilising researched theory and a simulation program of the recovery system. The simulation is control volume-based and generates property data on the fluid and exhaust gas throughout the heat exchanger. The final design included a finite element stress analysis of certain parts of the system to ensure safe testing at high pressures and temperatures. The final design resulted in a high pressure, cross flow, stainless steel fintube heat exchanger that, by using a continuous combustion unit as energy source and water as the working fluid, reached efficiencies of up to 74% in direct steam generation testing. The tube-side of the heat exchanger was designed to withstand pressures of up to 2MPa (20bar), which is imperative for the implementation of the next phase, where a turbocharger will be connected to the heat exchanger. The completion of this part of the project has paved the way for further development and implementation of the heat recovery system.AFRIKAANSE OPSOMMING: Die herwinning van energie begin 'n toenemend belangrike rol in die ingenieurs industrie speel. Die herwonne energie word in fabrieke ben ut en spaar maatskappye milj oene aan uitgawes per jaar. Hierdie beginsel word nie net in die grootskaalse nywerhede toegepas nie, maar ook in die allerdaagse lewe, soos byvoorbeeld in voertuie waar turbo-aanjaers gebruik word om die energie-uitset van enjins te verhoog deur bloot gebruik te maak van die verlore energie wat saam met die uitlaatgasse in die atmosfeer gepomp word. Die doel van hierdie projek is om 'n kleinskaalse energieherwinningstelsel te ondersoek en die mees effektiewe metode te vind om die herwinde energie na elektriese energie om te skakel wat as 'n sekondere energiebron gebruik kan word. Die navorsing bevat in die tesis, kyk na al die hoofkomponente en teoretiese kennis wat nodig is vir die konstruksie van 'n kleinskaalse hitteherwinningstelsel. Ook ingesluit is 'n teoretiese analise ten opsigte van die ontwerp en konstruksie van die sisteem. Dit behels die gebruik van nagevorsde teorie saam met 'n simulasie program van die herwinnings stelsel. Die simulasie program is op kontrole volumes gebasseet en genereer uitlaatgas- en water eienskappe soos dit deur die hitteruiler vloei. Die finale ontwerp bevat 'n eindige element spannmgs analise van sekere kritiese komponente in die stelsel om die veilige gebruik van die sisteem by hoe drukke en temperature te verseker. Die finale ontwerp was 'n hoedruk, kruisvloei, vlekvrye staal finbuis hitteruiler. Deur 'n konstante verbrandingseenheid as energiebron te gebruik saam met water as werksvloeier, het die hitteruiler effektiwiteite van tot 74% in direkte stoomgenerasie-toetse bereik. Die hitteruiler is ontwerp om hoe drukke van tot 2MPa (20bar) te hanteer wat baie belangrik is vir die implementasie van die volgende fase van die projek waar 'n turbo-aanjaer aan die stelsel gekoppel sal. Die suksesvolle voltooiing van hierdie fase van die projek het die weg gebaan vir die verdere ontwikkeling en implimentasie van die energieherwinningsstelsel

RNA editing in mesothelioma: a look forward

RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy

Viral Mimicry Response Is Associated With Clinical Outcome in Pleural Mesothelioma

Introduction: The aim of this study was to investigate endogenous retrovirus (ERV) expression and type I interferon (IFN) activation in human pleural mesothelioma (PM) and their association with clinical outcome. Methods: The expression of ERV was determined from PM cohorts and mesothelial precursor RNA sequencing data. The expression of ERV was confirmed by quantitative polymerase chain reaction (qPCR). Methylation of genomic DNA was assessed by quantitative methylation-specific PCR. DNA demethylation was induced in cells by demethylating agent 5-Aza-2’-deoxycytidine (5-Aza-CdR) treatment. To block type I IFN signaling, the cells were treated with ruxolitinib or MAVS silencing. The expression of IFN-stimulated genes (ISGs) was determined by qPCR and Western blot. Circulating ERVs were detected by qPCR. Results: Long terminal repeats (LTRs) represent the most abundant transposable elements up-regulated in PM. Within the LTR, ERVmap_1248 and LTR7Y, which are specifically enriched in PM, were further analyzed. The 5-Aza-CdR treatment increased the levels of ERVmap_1248 expression and induced ERVmap_1248 promoter demethylation in mesothelial cells. In addition, ERVmap_1248 promoter was more demethylated in the mesothelioma tissue compared with nontumor tissue. The 5-Aza-CdR treatment of the mesothelial cells also increased the levels of ISGs. Basal ISG expression was higher in the mesothelioma cells compared with the mesothelial cells, and it was significantly decreased by ruxolitinib treatment or MAVS silencing. Furthermore, ISG expression was higher in the tumor tissue with high expression levels of ERVmap_1248. High expression of ERVmap_1248 was associated with longer overall survival and BAP1 mutations. ERVmap_1248 and LTR7Y can be detected in the PM plasma. Conclusions: We provide clues for patient stratification especially for immunotherapy where best clinical responses are associated with an activated basal immune response.ISSN:2666-364

Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development

Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV (“MesoERV1-12”) were identified and verified by qPCR in mouse tissues. “MesoERV1-12” expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. “MesoERV1-12” levels were significantly increased by demethylating agent 5-Aza-2′-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. “MesoERV7” promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.ISSN:0304-3835ISSN:1872-798