Formation of the pro-apoptotic death-inducing signaling complex (DISC) can be initiated in cancer cells via binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to its two pro-apoptotic receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2. Primary components of the DISC are trimerized TRAIL-R1/-R2, FADD, caspase 8 and caspase 10. The anti-apoptotic protein FLIP can also be recruited to the DISC to replace caspase 8 and form an inactive complex. Caspase 8/10 processing at the DISC triggers the caspase cascade, which eventually leads to apoptotic cell death. Besides TRAIL, TRAIL-R1- or TRAIL-R2-selective variants of TRAIL and agonistic antibodies have been designed. These ligands are of interest as anti-cancer agents since they selectively kill tumor cells. To increase tumor sensitivity to TRAIL death receptor-mediated apoptosis and to overcome drug resistance, TRAIL receptor ligands have already been combined with various therapies in preclinical models. In this review, we discuss factors influencing the initial steps of the TRAIL apoptosis signaling pathway, focusing on mechanisms modulating DISC assembly and caspase activation at the DISC. These insights will direct rational design of drug combinations with TRAIL receptor ligands to maximize DISC signaling. © 2009 Elsevier B.V. All rights reserved.
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De veelheid van eisen enerzijds en verbindingstechnieken anderzijds maken een juiste keuze van het verbindingsproces moeilijk. De FME heeft het initiatief genomen om samen met andere partijen als de FDP, TNO, Syntens, NIMR, NIL, TU-Delft en Universiteit Twente, te komen tot kennisoverdracht op dit gebied. Dit initiatief is ondersteund door een financiële bijdrage van het Ministerie van Economische zaken (SenterNovem) en heeft geleid tot vele publicaties en de ontwikkeling van de website www.dunneplaat-online.nl. Via deze website kan de gebruiker komen tot de selectie van een verbindingsproces voor zijn specifieke situatie. Ten aanzien van het verbinden geldt de proceskeuze voor een materiaaldikte van 0,3 mm tot 3 mm, terwijl voor het lassen de proceskeuze geldig is voor materiaaldikten van 0,3 tot 20 mm. De verbindingsproceskeuze matrix wordt voortdurend aangevuld met de laatste ontwikkelingen en beschikbare informatie (nieuwe materialen, nieuwe verbindingsprocessen), zodat de gebruiker altijd verzekerd is van de meest recente informatie.
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In this report, the details of an investigation into the e ect of the low induction wind turbines on the Levelised Cost of Electricity (LCoE) in a 1GW o shore wind farm is outlined. The 10 MW INNWIND.EU conventional wind turbine and its low induction variant, the 10 MW AVATAR wind turbine, are considered in a variety of 10x10 layout configurations. The Annual Energy Production (AEP) and cost of electrical infrastructure were determined using two in-house ECN software tools, namely FarmFlow and EEFarm II. Combining this information with a generalised cost model, the LCoE from these layouts were determined. The optimum LCoE for the AVATAR wind farm was determined to be 92.15 e/MWh while for the INNWIND.EU wind farm it was 93.85 e/MWh. Although the low induction wind farm o ered a marginally lower LCoE, it should not be considered as definitive due to simple nature of the cost model used. The results do indicate that the AVATAR wind farms require less space to achieve this similar cost performace, with a higher optimal wind farm power density (WFPD) of 3.7 MW/km2 compared to 3 MW/km2 for the INNWIND.EU based wind farm.
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Summary of the article on the visit to Ukraine by students and teachers of the Secondary Teacher Training College Sittard (Part of Fontys University of Applied Sciences), by Maurice Heemels. In march 2009 a delegation of students and teachers of the Secondary Teacher Training College Sittard visited Ukraine. Their goal was to learn about the Holocaust in Ukraine between 1941 and 1944 and to experience how Ukrainian teachers deal with this topic in school nowadays. The delegation learned that teaching Ukrainian children about the Holocaust in their country is still in an early stage. But that can be seen a very positive, because for many years the Holocaust was a 'forbidden topic'. During the Soviet years talking and writing about the Holocaust was almost impossible and even after Ukraine had become independent (1991) it was rather unusual to do so. One of the other reasons why the Holocaust was rarely spoken about, was probably the fact that many Ukrainians had supported the German occupants in persecuting their Jewish neighbours. As a matter of fact, the persecution of Jews in Eastern parts of Europe was even more inhumane and violent than in Western Europe. Ukraine is full of places connected with this horrible part of its history. Until recently many Ukrainians, especially younger ones, didn't even seem to know the meaning of the word 'Holocaust' itself. Since a few years however, Ukrainian and foreign historians have begun to write about this almost unknown part of the Ukrainian history. And in schools, teachers have carefully begun to tell their students about it. Ukrainian history teacher Olexandr, 'Sacha' Voytenko travels through his immense country to inspire his colleagues in teaching about the Holocaust. In a quite impressive workshop he showed our delegation several ways 'to do it'. The time spent in Ukrainian classrooms on the topic is still relatively small, but can - regarding the past years of 'absolute silence' - be seen as an important break-through. The article will be published in: Kleio, Tijdschrift van de Vereniging van docenten Geschiedenis en staatsinrichting in Nederland (Dutch association of teachers and students of history), volume 7, november 2009.In maart van dit jaar bezochten studenten geschiedenis en docenten van de Fontys Lerarenopleiding Sittard Oekraïne. Ze deden dat samen met andere Nederlandse en Belgische studenten en docenten om meer te weten te komen over de Holocaust in het land en de omgang met dit pijnlijke thema in het Oekraïense geschiedenisonderwijs. Dit artikel is een verslag van de bevindingen van de Limburgse delegatieleden.
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Demographic changes, such as the ageing of society and the decline of the birth rate, are gradually leading to the loss of valuable knowledge and experience in the Dutch Labour market. This necessitates an explicit focus on workers' sustainable employment so that they can add value to the organisation throughout their career. This study looks into the way in which the workers' motivation might affect their investments into their own sustainable employment. It was conducted in a major industrial service provider, Sitech Services. The conclusion is that intrinsic motivation plays an important role in both younger and older employees, and that the younger workers undertake more action in order to give physical form to their sustainable employment than their older colleagues.
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Pauses in speech may be categorized on the basis of their length. Some authors claim that there are two categories (short and long pauses) (Baken & Orlikoff, 2000), others claim that there are three (Campione & Véronis, 2002), or even more. Pause lengths may be affected in speakers with aphasia. Individuals with dementia probably caused by Alzheimer’s disease (AD) or Parkinson’s disease (PD) interrupt speech longer and more frequently. One infrequent form of dementia, non-fluent primary progressive aphasia (PPA-NF), is even defined as causing speech with an unusual interruption pattern (”hesitant and labored speech”). Although human listeners can often easily distinguish pathological speech from healthy speech, it is unclear yet how software can detect the relevant patterns. The research question in this study is: how can software measure the statistical parameters that characterize the disfluent speech of PPA-NF/AD/PD patients in connected conversational speech?
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Hoofdstuk 12 uit deel III: Uses of cultural technologies. The essays in this volume discuss both the culture of technology that we live in today, and culture as technology. Within the chapters of the book cultures of technology and cultural technologies are discussed, focussing on a variety of examples, from varied national contexts. The book brings together internationally recognised scholars from the social sciences and humanities, covering diverse themes such as intellectual property, server farms and search engines, cultural technologies and epistemology, virtual embassies, surveillance, peer-to-peer file-sharing, sound media and nostalgia and much more. It contains both historical and contemporary analyses of technological phenomena as well as epistemological discussions on the uses of technology.
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ObjectivesSeveral surgical techniques are available for the treatment of cervical degenerative disease. For resolving cervical nerve root compression, anterior cervical discectomy with fusion (ACDF) or posterior cervical foraminotomy (PCF) can be applied. Amongst neurosurgeons, there seems to be a tendency to prefer ACDF, even though there are some advantages in favor of PCF. The objective of present study is to evaluate which factors determine the choice for an anterior or posterior surgical approach in patients with cervical radiculopathy based on foraminal pathology.MethodsA web-based survey was sent to all 133 neurosurgeons in the Netherlands. The study followed a mixed methods cross-sectional design. The first part of the survey focused on general perceived (dis)advantages of ACDF and PCF. The second part concerned questions about the choice between the two procedures. Furthermore, it was analyzed if exposure during training, amount of performed surgeries, assumed reoperation and complication rates influenced the choice of procedure by conducting Chi-square tests with post-hoc analysis.ResultsA total of 56 neurosurgeons responded (42%). An overall preference for ACDF was observed, even when differentiating for a pure disc prolapse, a spondylotic or a combined stenosis of the neuroforamen. The most relative important factors for motivating the preference for either ACDF or PCF were: the assumed best decompression of the nerve root (18%), congruence with current literature (16%), exposure during residency (12%), personal comfort (11%) and experience (11%) with the technique.ConclusionIn this survey, there was an overall preference for ACDF above PCF for the surgical treatment of a foraminal cervical radiculopathy. In addition to subjective factors as “experience” and “comfort”, the respondents often motivated their choice as “the best one according to literature”. As there is currently no evidence about the superiority of any of the procedures in literature, this assumption is remarkable.
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Of all patients in a hospital environment, trauma patients may be particularly at risk for developing (device-related) pressure ulcers (PUs), because of their traumatic injuries, immobility, and exposure to immobilizing and medical devices. Studies on device-related PUs are scarce. With this study, the incidence and characteristics of PUs and the proportion of PUs that are related to devices in adult trauma patients with suspected spinal injury were described. From January–December 2013, 254 trauma patients were visited every 2 days for skin assessment. The overall incidence of PUs was 28⋅3% (n = 72/254 patients). The incidence of device-related PUs was 20⋅1% (n = 51), and 13% (n = 33) developed solely device-related PUs. We observed 145 PUs in total of which 60⋅7% were related to devices (88/145). Device-related PUs were detected 16 different locations on the front and back of the body. These results show that the incidence of PUs and the proportion of device-related PUs is very high in trauma patients
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Bij de aanvang van het lectoraat 'sociale infrastructuur en technologie' was onze doelstelling te komen tot een inventarisatie van ict gebruik in de sociale sector. Daarbij ging het ons om praktijken en initiatieven in de sociale sector waarbij men gebruik maakt van moderne technologie ter versterking van de sociale infrastructuur, de leefbaarheid van samenlevingsverbanden, de participatie in de publieke besluitvorming, de hulp- en dienstverlening aan cliknten en deelnemers. Met de sociale sector worden alle institutionele arrangementen bedoeld die het werken aan welzijn als primaire doelstelling hebben. Het gaat hierbij niet om een zoveelste onderzoek teneinde een volledig, kwantitatief gericht beeld te krijgen. Er werd gestreefd naar een beschrijving van veelbelovende aanpakken, niet alleen binnen de institutionele welzijnszorg, maar ook projecten en activiteiten die op initiatief van burgers buiten de sociale sector-in strikte-zin zijn opgezet.
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