The clinical significance of the host immunologic competence and related angiogenesis and necrosis in the tumor microenvironment of hepatobiliary cancer

The incidence of hepatobiliary cancer has increased worldwide in recent years. These tumor entities translate into high recurrence and mortality rates, poor prognosis and clinical outcome. The management of hepatobiliary cancer is challenging and demands in most cases referral to a specialized high volume center where meticulous therapeutic interventions and advanced surgery can be performed. Unfortunately, only limited therapeutic modalities are available and curative surgery or LTX are often precluded due to the advanced disease at time of diagnosis. In this palliative setting, chemotherapy, radiation or best supportive care remain the only pillars of medical care. There is an urgent unmet need for adjunct therapeutic modalities for hepatobiliary cancer. Hereby, the role of the host immune system, after falling into desuetude in the past, has been nowadays increasingly recognized as a powerful tool in the armamentarium of available options. Overwhelming data demonstrates the formidable ability of various entities of the innate and adaptive immune system not only to be efficiently applied as vectors of anticancer treatment, but also help refine the diagnostic strategies. The latter translates into improved risk stratification and enhanced ability to identify subgroups of patients with negative tumor profiles and poor prognosis. Taken together, these insights can help enhance the efficacy of cancer management and deliver more individualized approaches in an era of personalized medicine. In the current studies, we were able to demonstrate the prognostic significance of various aspects of the host immune system and establish links that presume functional networks. This enabled us to outline them as an autonomous immunologic construct in the setting of human cancer. The main conclusions were that tumor-infiltrating monocytes/macrophages subtypes, related angiogenesis vectors and the formation of histologic necrosis in the tumor microenvironment are strongly associated. This coherent immunologic construct exerted a significant influence on patients’ overall and recurrence-free survival and qualified as an independent marker of predictiveness. The presented studies generated data that could help efficiently categorize patients in subgroups of increased risk for unfavorable clinical outcome. Furthermore, these results may represent a novel molecular pathway for immunologic checkpoint inhibition in human hepatobiliary cancer. Future studies are needed to better explore and define the implied mechanistic links, which will not only facilitate a better understanding of the tumor biology, but also optimize the management of cancer

Concept Introduction: 70 PAX Plug-In Hybrid-Electric Aircraft (D70-PHEA)

The presentation is a part of the Mid-Term Review of the internal DLR project EXACT. The mid term review was organized as a public event for an international audience. The document describes the overall aircraft design results of a 70-seater plug-in hybrid-electric aircraft, featuring fully battery-electric flight capability, a gas turbine driving a generator that can be used as a range extender, and eight electric propellers distributed along the wing span. As all aircraft designes for EXACT, the assumed entry into service is 2040

Comparison of Sustainable Regional Aircraft Concepts

The presentation shows a comparison between three 70-seater aircraft concepts calculated within the DLR's internal EXACT project. All three concepts assume an entry into service of 2040 and are designed for operation with sustainable energy. The first concept is propelled with advanced turboprop engines fuelled by synthetic kerosene. The second concept is powered by fuel cells driven by liquid hydrogen. The third concept is a plug-in hybrid, i.e. a battery-electric aircraft with a gas turbine driving a generator that can be used as a range-extender. The three concepts are compared in terms of energy efficiency. The results show that the fuel cell aircraft requires around 30% less energy for average fleet operation, whereas the plug-in aircraft requires almost 50% less energy

Aircraft Modeling Results, Short-Range Turboprop Baselines (D250-321TP-2040, D220-320TP-2040)

The presentation is a part of the Mid-Term Review of the internal DLR project EXACT. The mid term review was organized as a public event for an international audience. The document describes the overall aircraft results of a 250-seater turboprop aircraft family. As all aircraft designes for EXACT, the assumed entry into service is 2040

Plug-In Hybrid-Electric Regional Aircraft Concept for IMOTHEP

The presentation desribes a 40-seater plug-in aircraft concept, designed for IMOTHEP, an international project funded by Horizon 2020. The concept is designed for entry into service of 2035. The plug-in aircraft architecture features a fully battery-electric flight capability, a gas turbine driving a generator that can be used as a range extender, and eight electric propellers distributed along the wing span. The key-performance indicator for the aircraft of the 40-seater class in IMOTHEP is the energy consuption at 200nm. Due to the fully electric flight capability at this range, the plug-in configuration requires 60% less energy than a comparable turboprop aircraft

70 PAX Fuel Cell Aircraft D70-FCLH2-2040

The presentation is a part of the Mid-Term Review of the internal DLR project EXACT. The mid term review was organized as a public event for an international audience. The document describes the overall aircraft results of a 70-seater fuel-cell-driven aircraft, featuring 10 electric propellers distributed across the wing span. As all aircraft designes for EXACT, the assumed entry into service is 2040

On the Mechanism of Water Electrolysis

A two stage model of the physicochemical processes at the electrolysis of pure water is proposed. The presence of nascent hydrogen in the catholyte and nascent oxygen in the anolyte during the first stage explains the antioxidant properties of the catholyte and the strong biocidal action of the anolyte. In the second stage the nascent hydrogen and oxygen are combined into hydrogen and oxygen molecules, respectively. The comparison between their average energies with the average energy of the control sample of water shows an increase in the average energy of the catholyte and decrease in the average energy of the anolyte. This indicates that some changes in the structure of the activated water have occurred. Keywords: Electrochemically activated water (ECAW), catholyte, anolyte, nascent hydrogen, nascent oxygen, energetic spectrum, energy of hydrogen bonds

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

BACKGROUND: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival. RESULTS: Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05). CONCLUSIONS: Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis-TEM-angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC

Architectural Trade-offs for a Hybrid-Electric Regional Aircraft

Research entities and the aviation industry are collaborating to reduce the greenhouse gas emissions of the global aircraft fleet. To move away from fossil fuels as energy carrier while reducing the aircrafts primary energy demand are the ideal but challenging means to achieve this target. The research activities within the German government funded project TELEM have shown on a conceptual level that both measures could be realized for regional aircraft with an optimized hybrid-electric propulsion (HEP) ar- chitecture. Short, but very frequently flown distances of 200 nm and more could be served fully electri- cally by advanced propeller-driven aircraft with an assumed entry-into-service (EIS) in 2035. This paper gives an overview of integration concepts pursued in the project and reflects on various design aspects of a plug-in hybrid-electric aircraft, featuring a fully electric flight capability and a kerosene-fueled tur- boshaft range-extender. The aircrafts HEP architecture is optimized with regard to the number of pro- pellers, as well as range extenders and their integration concept as to yield the best efficiency and to enable commonality with smaller aircraft leading to potential cost reductions among aircraft classes. Furthermore, a thermal management system, which is essential for the hybrid-electric propulsion archi- tecture and its requirements are discussed and a favorable option selected. The final configuration fea- tures ten propellers and one range extender. The results also confirmed the exceptional efficiency of a plug-in HEP architecture for regional aircraft, showing a 34.6 % reduction in fleet energy and 64.4 % reduction in fuel consumption compared to a conventional turboprop architecture with an EIS in 2035

Vlianie na mancozeba vurhu reprodukciata na dugova pusturva (Oncorhynchus mykiss W.) i natrupvane na negovia kancerogenen metabolit etilen tiourea v ribnite produkti

Pesticides can be taken up from the water and accumulated in tissues of hydrobionts, often becoming multiplied thousands of times higher in the organism than in the surrounding water. The dithiocarbamate mancozeb is applied in plant protection as fungicide. In recent years the amount of mancozeb used in Europe significantly increased. It is carcinogen due to its metabolite - ethylene thiourea (ETU), which causes thyroid and pituitary tumors. The purpose of this study is to determinate the quantity of ethylene thiourea in products of rainbow trout (Oncorhynchus mykiss W.), reared in environment containing permissible, according to the European law, amount of mancozeb. Seeking an answer to the question: is this concentration limit really safe for the reproduction of rainbow trout and can the more toxic metabolite - ETU, be accumulated in the fish eggs and fillet and afterwards make them harmful to the consumers? The study included 3 stages: feeding, analysis of ethylene thiourea in fish eggs and fillet by a new developed and validated HPLC (high performance liquid chromatography) method and study of the reproductive indicators. The assays of ETU in all analyzed samples (fish and water) were below the limit of quantification of the method, 0.05 mg*l-1, so fish do not accumulate the carcinogen degradation product of mancozeb and the maximum residue level of mancozeb is really safe for the humans as consumers. But these environmental conditions caused reproductive disorders. They can be partly compensated by using sperm activation medium for artificial insemination of trout eggs, but successful fertilization does not guarantee successful hatching, especially of eggs in trout farms with presence of mancozeb in water, even in allowable concentration. The presented results confirm previous investigation, that Salmonidae are very sensitive fish species, react to the lowest deviations in concentration levels of xenobiotics and are used for indicator of non-polluted water.Pesticidite, popadnali vuv vodoemite, mogat da se poemat ot obitavashtite gi hidrobionti. Te sa v systoqnie da gi natrupat v svoite tukani i tiahnata koncetracia da se uvelichi, dori hiliadi puti, sravnena s tazi vuv vodata. Ditiokarbamatut mancozeb se prilaga v rastitelnata zashtita kato fungicide. Prez poslednite godini negovoto izpolzvano v Evropa kolichestvo znachitelno narasna. Kancerogennostta na mancozeba se dulji na metabolita mu, etilen tiourea (ETU), koiato prichiniava tumori na shtitovidnata jleza i hipofizata. Celta na tova izsledvane e da se opredeli sudurjanieto na etilen tiourea v produkti ot dugova pusturva (Oncorhynchus mykiss W.), otglejdana v sreda, sudurjashta dopustimo, suglasno evropejskoto zakonodatelstvo, kolichestvo mancozeb. Tursen e otgovor na vuprosa: tazi dopustima koncentracia naistina li e bezopasna za reprodukciata na dugovata pusturva i moje li da bude natrupan po-toksichniat metabolit - ETU, v haivera i fileto, koeto da gi napravi vredni za potrebitelite? Tova prouchvane vklyuchva 3 etapa: hranene, analiz na etilen tiourea v haiver i ribno file chrez novo razraboten i validiran HPLC (visokoefektivna techna khromatografia) metod i izsledvane na reproduktivnite indikatori. Kolichestvoto na ETU vuv vsichki analizirani probi (riba i voda) pokazaha sudurvanie pod granicata na kolichestveno opredeliane na metoda, 0.05 mg*l-1; ribata ne natrupva kancerogennia product na razgrajdane na mancozeba i maksimalno dopustimata mu koncentracia e naistina bezopasna za potrebitelite. Tezi uslovia na okolnata sreda obache prichiniavat reproduktivni razstroistva. Te mogat da budat chastichno kompensirani chrez izpolzvane na spermo-aktivacionna sreda za iskustveno osemeniavane na haiver ot pusturva. No uspeshnoto oplojdane ne garantira uspeshnoto izlyupvane, osobeno na haiver v pusturvovi stopanstva s nalichie na macozeb vuv vodata, dori v dopustimata koncentracia