47 research outputs found

    Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

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    A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis

    Human performance and strategies while solving an aircraft routing and sequencing problem: an experimental approach

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    As airport resources are stretched to meet increasing demand for services, effective use of ground infrastructure is increasingly critical for ensuring operational efficiency. Work in operations research has produced algorithms providing airport tower controllers with guidance on optimal timings and sequences for flight arrivals, departures, and ground movement. While such decision support systems have the potential to improve operational efficiency, they may also affect users’ mental workload, situation awareness, and task performance. This work sought to identify performance outcomes and strategies employed by human decision makers during an experimental airport ground movement control task with the goal of identifying opportunities for enhancing user-centered tower control decision support systems. To address this challenge, thirty novice participants solved a set of vehicle routing problems presented in the format of a game representing the airport ground movement task practiced by runway controllers. The games varied across two independent variables, network map layout (representing task complexity) and gameplay objective (representing task flexibility), and verbal protocol, visual protocol, task performance, workload, and task duration were collected as dependent variables. A logistic regression analysis revealed that gameplay objective and task duration significantly affected the likelihood of a participant identifying the optimal solution to a game, with the likelihood of an optimal solution increasing with longer task duration and in the less flexible objective condition. In addition, workload appeared unaffected by either independent variable, but verbal protocols and visual observations indicated that high-performing participants demonstrated a greater degree of planning and situation awareness. Through identifying human behavior during optimization problem solving, the work of tower control can be better understood, which, in turn, provides insights for developing decision support systems for ground movement management

    A Kinase-Phosphatase Network that Regulates Kinetochore-Microtubule Attachments and the SAC

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    Why Air Traffic Controllers Accept or Refuse Automated Technology

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    Increased utilisation of automation is seen as a potential, if not the most likely solution to cope with the forecasted increase in air traffic (SESAR, 2006; FAA, 2010). However, Air Traffic Controller Operators (ATCOs) are very selective about forms of automated assistance (EUROCONTROL, 2000). Automation acceptance is considered crucial for the successful implementation of any new technology within air traffic management and therefore is one of the largest challenges the industry faces (Hilburn & Flynn, 2001). Since traditional predictors of automation acceptance such as trust and job satisfaction appear to be diminishing (Bekier, Molesworth & Williamson, in press), the main aim of the present research was to identify the factors that help to explain ATCOs willingness to accept more mature forms of automated assistance. The results revealed that ATCOs value automation that is user-friendly, removes ‘boring’ and ‘standardized’ tasks, and importantly keeps them cognitively challenged in their role

    Przemiany związków azotu w kompostach produkowanych ze stałych odpadów miejskich

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    The aim of the research was to estimate the direction and intensity of nitrogen transformations in composts produced from municipal solid wastes (MSW), including time, composting parameters and composting technology. Objects of studies were composts at different maturity stages, produced according to two different technologies: MUT-DANO in Katowice and KKO-100 in Zielona Gora. In collected samples the following determinations were performed: temperature, humidity, pH in KCl, Corg – total organic carbon, Nt – total nitrogen, Nw – water soluble nitrogen, N-NH4 + and N-NO3 – in water extracts (compost to water ratio 1:10). Obtained results show that during composting of MSW the amounts of Nt and N-NO3 – increased while those of Nw and N-NH4 + decreased. Intensity of those changes was statistically confirmed and correlated with composting conditions. Prolonged anaerobic conditions in material from Katowice inhibited nitrification processes, which was confirmed by higher N-NH4 +/N-NO3 – ratio. To take into consideration the value of this rate, compost from Katowice did not reach maturity even after 180 days of composting.Celem przeprowadzonych badań było okreoelenie kierunków intensywności procesów transformacji azotu w kompostach produkowanych z odpadów miejskich z uwzględnieniem czasu i warunków kompostowania oraz zastosowanej technologii. Badaniami objęto komposty wytwarzane z odpadów miejskich według odmiennych technologii: MUT-DANO w Katowicach i KKO-100 w Zielonej Górze. W celu poznania warunków procesów przemian azotu, wykonano oznaczenia: temperatury, wilgotnooeci aktualnej, pH w KCl, Corg – węgla organicznego, Nog – azotu ogółem, Nw – azotu wodnorozpuszczalnego (kompost: woda jak 1:10), N-NH4 + i N-NO3 – w ekstraktach wodnych (1:10). Wyniki badań wykazały, iż w czasie kompostowania odpadów miejskich następuje wzrost zawartooeci Nog i N-NO3 – oraz obniżenie zawartooeci Nw i N-NH4 +. Intensywność tych zmian, zależała od warunków kompostowania. Przedłużone warunki beztlenowe w materiale kompostowanym w Katowicach, hamowały procesy nitryfikacji, co wyrażało się zmniejszeniem ilooeci formy N-NO3 – w stosunku do N-NH4 +. Biorąc pod uwagę indeks N-NH4 +/N-NO3 –, kompost produkowany w Katowicach nie osiągnął stanu pełnej dojrzałooeci nawet po 180 dniach kompostowania

    Wpływ uwilgotnienia odpadów komunalnych na przemiany form azotu w czasie kompostowania

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    The aim of the study was to determine the influence of municipal wastes moisture level of on the intensity of transformations of various forms of nitrogen during composting. The object of the study was fresh (heating) compost leaving the technological line of the composting plant MUT-DANO in Katowice. Composting of that material was conducted for a period of 5 months under the following conditions: variant A -pile on plastic foil, with moisture content of 0.5 kg H2O kg-1 dm, variant B - perforated plastic container of ca 1 m3 in capacity. with moisture content of 0.5 kg H2O kg-1 dm, variant C - perforated plastic container of 1 m3 in capacity. with moisture content of 0.6 kg H2O kg-1 dm. The composted material was stirred at intervals of 10-15 days for aeration, moisture content of the material was determined, water deficit was replenished, and samples were taken for laboratory analyses. In collected samples the following determinations were performed: humidity, ash content, contents of different nitrogen forms: Nt - total nitrogen, Nw - water-soluble nitrogen (1:10), N-NH4+ and N-NO3- - mineral nitrogen in water extract. Nw org. - organic nitrogen in water extract. Based on this results the total nitrogen losses were calculated. Obtained results shows that moisture of composted municipal wastes plays an important role in the shaping of the fertility properties of composts and determines the content of total N and the transformation of its organic and mineral forms. Composting of municipal wastes on the pile, accelerated the maturation of composts and was conducive to the obtainment of product richer in nitrogen, with a higher content of N-NO3-. Also higher moisture content of composted municipal wastes did not ensure their sufficient oxygenation, which led to grater losses of nitrogen, reduced the quality of compost, and did not ensure sanitary safety. Higher moisture content limited and modified the rate of biochemical transformations in composted municipal wastes.Analizowano wpływ uwilgotnienia komunalnych odpadów miejskich na szybkość przemian różnych form azotu w czasie kompostowania. Kompostowanie materiału grzejnego opuszczającego linię technologiczną kompostowni MUT-DANO prowadzono przez okres 5 miesięcy w następujących warunkach: A - na pryzmie przy uwilgotnieniu 0,5 kg H2O o kg-1 s.m., B - w pojemnikach ażurowych przy uwilgotnieniu 0,5 kg H2O o kg-1 s.m.. C - w pojemnikach litrowych przy uwilgotnieniu 0,6 kg H2O o kg-1 s.m. w dniach napowietrzania. Materiał mieszano w odstępach 10-15-dniowych, uzupełniano ubytki wody i pobierano próbki do badań. Oznaczono w nich: m wilgotność aktualną, zawartość popiołu oraz różnych form azotu: N-ogółem, N - w wyciągu wodnym (1:10), l N-NH4+ i N-NO3- w wyciągu wodnym. Na podstawie uzyskanych wyników obliczono straty azotu ogółem. Uzyskane wyniki badań wskazują, że poziom uwilgotnienia kompostowanych odpadów komunalnych odgrywa ważną rolę w kształtowaniu wartości nawozowej kompostów i decyduje o zawartości N-ogółem oraz transformacji jego form organicznych i mineralnych. Kompostowanie odpadów komunalnych na pryzmie ograniczało straty azotu, sprzyjało powstawaniu kompostów bardziej zasobnych w azot. o wyższej zawartości N-NO3-, gwarantowało ich pełne bezpieczeństwo sanitarne oraz decydowało o szybszym ich dojrzewaniu. Większe uwilgotnienie ograniczało i modyfikowało tempo przemian biochemicznych w kompostowanych odpadach komunalnych i zmieniało kierunek transformacji związków azotu. Zauważono, iż wyższa wilgotność kompostowanych odpadów komunalnych przyczyniała się do gorszego ich natlenienia i prowadziła do większych strat azotu, co obniżało wartość nawozową kompostu i nie gwarantowało bezpieczeństwa sanitarnego

    Antihistaminic action of nicotinamide

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