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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
In language switching, it is assumed that in order to produce a response in one language, the other language must be inhibited. In unimodal (spoken-spoken) language switching, the fact that the languages share the same primary output channel (the mouth) means that only one language can be produced at a time. In bimodal (spoken-signed) language switching, however, it is possible to produce both languages simultaneously. In our study, we examined modality effects in language switching using multilingual subjects (speaking German, English, and German Sign Language). Focusing on German vocal responses, since they are directly compatible across conditions, we found shorter reaction times, lower error rates, and smaller switch costs in bimodal vs. unimodal switching. This result suggests that there are different inhibitory mechanisms at work in unimodal and bimodal language switching. We propose that lexical inhibition is involved in unimodal switching, whereas output channel inhibition is involved in bimodal switching.
Cued language switching is used to examine language-control processes by comparing performance in language-switch trials with performance in repetition trials. In 1:1 cue-to-language mappings, language repetitions involve cue repetitions and language switches involve cue switches. Hence, the observed switch costs might reflect cue-switch costs rather than language-related control processes. By introducing a 2:1 cue-to-language mapping, we dissociated language switches (cue and language switched vs. cue switched, but language repeated) and cue switches (repeated language, with vs. without switched cue). We found cue-switch costs, but language-related switch costs were substantial, too, presumably reflecting language-control processes in cued language switching.
In the European Rosetta project three separate, previously developed, ICT systems were improved and integrated to create one modular system that helps community-dwelling people with mild cognitive impairment and dementia in different stages of the disease. The system aims to support them in daily functioning, monitor (deviations from) patterns in daily behaviour and to automatically detect emergency situations. The study aimed to inventory the end users’ needs and wishes regarding the development and design of the new integrated Rosetta system, and to describe the to be developed Rosetta system.
Qualitative user-participatory design with in total 50 persons: 14 people with dementia, 13 informal carers, 6 professional carers, 9 dementia experts, 7 care partners within the project, and 1 volunteer. In the Netherlands user focus group sessions were performed and in Germany individual interviews. Dementia experts were consulted by means of a questionnaire, an expert meeting session, and interviews.
Persons with dementia and informal carers appreciated the following functionalities most: help in cases of emergencies, navigation support and the calendar function. Dementia experts rated various behaviours relevant to monitor in order to detect timely changes in functioning, e.g. eating, drinking, going to the toilet, taking medicine adequately, performance of activities and sleep patterns. No ethical issues regarding the use of sensors and cameras were mentioned.
The user participatory design resulted in valuable input from persons with dementia, informal carers and professional carers/dementia experts, based on which a first prototype Rosetta system was built.
Stimuli used in cued language switching studies typically consist of digits or pictures. However, the comparability between both stimulus types remains unclear. In the present study, we directly compared digit and picture naming in a German–English language switching experiment. Because digits represent a semantic group and contain many cognates, the experiment consisted of four conditions with different stimulus sets in each condition: digits, standard language switching pictures, pictures depicting cognates, and semantically-related pictures. Digit naming caused smaller switch costs than picture naming. The data suggest that this difference can be attributed to phonology. Both methodological and theoretical implications are discussed.
Phylogenetic analyses suggest lyssaviruses, including Rabies virus, originated from bats. However, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. A number of genetically diverse lyssaviruses are present in Africa, including Lagos bat virus (LBV). A high seroprevalence of antibodies against LBV was detected in Eidolon helvum bats. Longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture–mark–recapture (CMR) analysis used to follow 98 bats over 18 months. These data demonstrate endemic infection, with evidence of horizontal transmission, and force of infection was estimated for differing age categories. The CMR analysis found survival probabilities of seronegative and seropositive bats were not significantly different. The lack of increased mortality in seropositive animals suggests infection is not causing disease after extended incubation. These key findings point towards acute transmission of bat lyssaviruses in adapted bat hosts that occurs at a far higher rate than the occurrence of disease.
Bat flies are obligate ectoparasites of bats and it has been hypothesized that they may be involved in the transmission of Bartonella species between bats. A survey was conducted to identify whether Cyclopodia greefi greefi (Diptera: Nycteribiidae) collected from Ghana and 2 islands in the Gulf of Guinea harbour Bartonella. In total, 137 adult flies removed from Eidolon helvum, the straw-coloured fruit bat, were screened for the presence of Bartonella by culture and PCR analysis. Bartonella DNA was detected in 91 (66·4%) of the specimens examined and 1 strain of a Bartonella sp., initially identified in E. helvum blood from Kenya, was obtained from a bat fly collected in Ghana. This is the first study, to our knowledge, to report the identification and isolation of Bartonella in bat flies from western Africa.
A Protestant among Catholics, a proud citizen of the tiny republic of Geneva among cosmopolitan fellow travellers of monarchical imperialism, a critic of modernity at its most fashionable eighteenth-century shrine, Rousseau was spiritually estranged from the intellectual circles in Paris to which he had previously been drawn when, in 1750, he won the prize offered by the Academy of Dijon by responding in the negative to its question, ‘Has the restoration of the arts and sciences contributed to the purification of morals?’ With the publication of this work, his First Discourse, he immediately became a celebrity and thereby launched his literary career as chief critic of the age of Enlightenment. When, in 1755, in addressing the same academy’s question, for another prize competition, on ‘What is the origin of inequality among men, and is it authorised by natural law?’, he condemned both the loss of innocence and lack of virtue prevalent in refined society. Private property, he asserted in his Second Discourse, was the principal source of that form of unnatural inequality which gives rise to governments, rulers, and violence.
Rousseau here, as well as in his Essay on the Origin of Languages largely drafted some years later (and first published posthumously in 1781), sketches a theory of historical development according to which mankind must originally have lived in a purely animal and unsociable state of nature, driven by hunger and sexual appetite alone. In that condition man’s only inclinations would have been self-love and compassion, Rousseau argues, but as the human race multiplied, this simple form of life would have disappeared.
We study a system of ordinary differential equations linked by parameters and subject to boundary conditions depending on parameters. We assume certain definiteness conditions on the coefficient functions and on the boundary conditions that yield, in the corresponding abstract setting, a right-definite case. We give results on location of the eigenvalues and oscillation of the eigenfunctions.
Some boron-rich (with respect to the Nd 2Fe,4B composition) NdFeB alloys (with and without small additions of zirconium) have been investigated in an attempt to understand the influence of zirconium in the subsequent magnetic properties of HDDR hot pressed magnets. It was found that zirconium additions had a marked influence on the as-cast microstructures with a general refinement of the grain size and evidence of a zirconium-rich phase (probably ZrB2) at the grain boundaries. The magnetic property measurements of fully dense, isotropic HDDR hot pressed magnets indicated that those containing zirconium maintained their coercivity to significantly higher hot pressing temperatures and this was attributed to the pinning of grain boundaries by the zirconium rich phase.
In an integrated group housing system for sows, animals of all stages of production are kept in one group, except around farrowing, and remain there throughout their productive life. Lactating sows have access to the suckling section of the house via an electronic gate. Jostling of piglets from different litters is avoided by keeping the litters in their own suckling pen until weaning. The system allows lactating sows to freely evade their piglets, and move between the suckling section and the communal area. They can maintain their social position and cool off in the relative cool communal area. Earlier observations (Houwers et al., 1992) showed sows decreased sucklings and increased their absence from the farrowing pen towards weaning. It was not clear whether the overall performance of the piglets was depressed by absence of sows before weaning. The relevance for practical farming partly depends on the production results that can be achieved.
Chronically stressed adult male Balb C mice were submitted to the tail suspension test. Chronic immobilization stress (6 h/d for 14 consecutive days) induced a significant reduction in immobility time when compared to non-stressed controls. Pretreatment with LY 53857, a serotonin 5HT2 antagonist, and IPS 339, a selective beta-2 adrenoceptor blocker, reversed immobility time to the levels of non-stressed controls. Chronic administration of corticosterone (100 mg/kg for 7 d) did not modify immobility time as compared to saline treated controls. It is suggested that both serotonergic and adrenergic pathways in the brain may participate in the stress-induced changes occurring in the tail suspension test response and that corticosterone does not appear to play a role in this process.
This study was designed to verify whether fluoxetine (FL), a serotonin (5-HT) re-uptake inhibitor, would interfere with nortriptyline (NT), a biphasic U-shaped curvilinear dose-response relationship recently described in our laboratory. We associated 10 mg/kg NT or vehicle to 0, 5, 10, 20 and 40 mg/kg FL, in one group, and 10 mg FL or vehicle to 0, 5, 10, 20 and 40 mg/kg NT, in another group, 30 min before the tail suspension test (TST) in mice. Although we were not able to confirm a synergistic effect between FL and NT, FL-NT association seems to require higher doses of NT to block its own anti-immobility effect at high doses, thus widening NT effective antidepressant-like dose range in mice submitted to TST.
A more systematic marketing research approach has finally revealed good ideas anticipating a market need for the use of shape memory alloys. The success of those new ideas, prototypes and applications are analysed in terms of “the value of the function”, defined as the importance of the function divided by the cost of providing the function. A high importance and/or a low cost of the function are thus the basic requirements for the successful introduction of shape memory applications. Attention is also paid to the way how the 4 P's, product, price, place, promotion (the marketing mix) are applied by the European companies. Those different items will be illustrated on the basis of some small-, medium- and largescale applications, used in different markets. “to the point research”, fundamental and applied, on material properties as well as on manufacturing (cost reduction) is being discussed as the key factor to increase the function value.
A method for trajectory control in the joint space is presented. An acceleration profile is proposed for each segment of the trajectory. After a twofold integration a position trajectory is obtained with advantageous characteristics. The position trajectory is completely dynamically balanced; it exhibits continuity up to the third derivative of the position. This way, minimum requirements are imposed on the actuators. The technique delivers predictable results since the trajectory deviates only slightly from a straight line connection between successive joint coordinates. Very limited computational effort is required.
As the first international project of this kind, the German-Dutch Wind tunnel (DNW) is under construction in the Noordoostpolder, The Netherlands. The DNW will be among the largest and most extensive complete low speed wind tunnels in Europe. This project is based on previous specifications and design work for two former national projects (now abandoned) which were similar in size and performance and mutually complementary in view of the tasks. The DNW will contribute to filling the gap still existing in the field of aeronautical test facilities in Europe for effective aircraft development work.
The DNW will consist of a closed circuit tunnel (total length of centre line: 318 m) with three interchangeable atmospheric test sections with cross-sectional sizes of 9.5m x 9.5 m, 8 m x 6m and 6 m x 6 m; the maximum speed is about 60, 110 and 145 m/s respec-tively. In addition, an open jet configuration will be available with special features for aero-acoustic tests. The single-stage speed-controlled fan of 12 m diameter has a nominal drive power of 12.7 MW. The standard equipment will include an air exchange system and a heat exchanger in the circuit, a model sting support, a six-component balance, and a distributed computer system for data acquisition/reduction and control purposes.
This paper deals with the facilities for landlall that can be provided by lighted aids to navigation. The relationship between the navigational errors of ships approaching from the open sea and the performance to be selected for a landfall light is worked out. The probabilities of a successful landfall in various circumstances are then analysed. Finally the limitations of light as the sole aid to navigation in the process of making a landfall are discussed. Rear Admiral van Hooff was for long head of the Netherlands Pilotage and Lighthouse Service; Ir. Sirks is technical director of the Netherlands Lighthouse Service.
A Marine terminal influences the flow of traffic which sails at a lower speed and is congested. Navigation must be in accordance with the total amount of traffic and not, as in the open sea, in accordance with one or two other ships. Shore based authority must be accepted. The flow of traffic along the coast passing a terminal meets this congestion, certainly if the terminal is in shallow water frequented by large vessels. Crossing also adds to the congestion for the passing flow of traffic. The congestion will be less if the marine terminal and outer channel can accommodate the total traffic flow.