A New Technique for Compensating Joint Limits in a Robot Manipulator

A new robust, optimal, adaptive technique for compensating rate and position limits in the joints of a six degree-of-freedom elbow manipulator is presented. In this new algorithm, the unmet demand as a result of actuator saturation is redistributed among the remaining unsaturated joints. The scheme is used to compensate for inadequate path planning, problems such as joint limiting, joint freezing, or even obstacle avoidance, where a desired position and orientation are not attainable due to an unrealizable joint command. Once a joint encounters a limit, supplemental commands are sent to other joints to best track, according to a selected criterion, the desired trajectory

APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5–6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53–DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter–luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury

Accuracy of UK Rapid Test Consortium (UK-RTC) "AbC-19 Rapid Test" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study.

OBJECTIVE: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Test accuracy study. SETTING: Laboratory based evaluation. PARTICIPANTS: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. MAIN OUTCOME MEASURES: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. RESULTS: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). CONCLUSIONS: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to "spectrum bias." Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. STUDY REGISTRATION: ISRCTN 56609224.The study was commissioned by the UK Government’s Department of Health and Social Care. It was funded and implemented by Public Health England, supported by the NIHR Clinical Research Network (CRN) Portfolio. The Department of Health and Social Care received a report containing these data on 10/9/2020, but had no role in the study design, data collection, analysis, interpretation of results, writing of the manuscript, or the decision to publish. DW acknowledges support from the NIHR Health Protection Research Unit in Genomics and Data Enabling at the University of Warwick. HEJ, AEA, MH and IO acknowledge support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. STP is supported by an NIHR Career Development Fellowship (CDF-2016-09-018). Participants in the COMPARE study were recruited with the active collaboration of NHS Blood and Transplant (NHSBT) England (www.nhsbt.nhs.uk). Funding for COMPARE was provided by NHSBT and the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024). The academic coordinating centre for COMPARE was supported by core funding from: NIHR BTRU, UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194) and the NIHR [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Division), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. JD holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care

The Journey Experience of Visually Impaired People on Public Transport in London

The use of public transport is critical for Visually Impaired People (VIP) to be independent and have access to out-of-home activities. Despite government policies promoting accessible transport for everyone, the needs of VIP are not well addressed, and journeys can be very difficult to negotiate. Journey requirements can often differ from those of other categories of people on the disability spectrum. Therefore, the aim of this research is to evaluate the journey experience of VIP using public transport. Semi-structured interviews conducted in London are used. The results show that limited access to information, inconsistencies in infrastructure and poor availability of staff assistance are the major concerns. Concessionary travel, on the other hand, encourages VIP to make more trips and hence has a positive effect on well-being. The findings suggest that more specific policies should be introduced to cater to the special needs of particular disabilities rather than generalising the types of aids available. It is also concluded that the journey experience of VIP is closely related to an individual’s independence and hence inclusion in society

Accuracy of UK Rapid Test Consortium (UK-RTC) “AbC-19 Rapid Test” for detection of previous SARS-CoV-2 infection in key workers: test accuracy study

Abstract: Objective: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: Test accuracy study. Setting: Laboratory based evaluation. Participants: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. Main outcome measures: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. Results: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). Conclusions: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to “spectrum bias.” Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. Study registration: ISRCTN 56609224

Classification of current anticancer immunotherapies

© 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.info:eu-repo/semantics/publishedVersio

Usages de l'automobile ; 5 phases européennes de mesures sur véhicules avec du matériel embarqué

5 measurement campaigns on vehicle uses and operating conditions were carried out: 2 in France in 1983 and 1989, and 3 European phases - Great-Britain, Germany and France - in 1990. Private vehicles were equipped with data acquisition systems and were driven by their owners for their normal purposes. Tests were performed over 114 vehicles, 140 000 kilometers and 18 000 trips travelled. Vehicle speeds and engine operating conditions were recorded at one-second time intervals.Vehicle uses and operating conditions were analyzed during the 5 measuring phases: daily use frequencies, trip characteristics (lengths, durations, etc.), speeds experienced.The analysis of instantaneous speeds and accelerations allowed the construction of representative test cycles for measuring pollutant emissions and fuel consumption on a test bench.Cinq campagnes de mesure des conditions d'usage et de fonctionnement des véhicules ont été menées : 2 en France en 1983 puis 1989, et 3 phases européennes - France, Grande-Bretagne et Allemagne - en 1990. Des véhicules privés étaient équipés d'un matériel d'acquisition de données, et utilisés en usages habituels par leur propriétaire. L'ensemble des mesures concerne 114 véhicules testés, 140.000 kilomètres parcourus et 18.000 trajets, au cours desquels sont connus à chaque seconde la vitesse du véhicule et les conditions de fonctionnement du moteur.Les usages et conditions de fonctionnement des véhicules sont analysés sur l'ensemble des 5 phases : fréquences journalières des utilisations, caractéristiques des trajets (longueurs, durées, etc.), vitesses pratiquées.L'analyse des vitesses et accélérations instantanées permet la construction de cycles d'essais représentatifs pour la mesure des émissions de polluants et de la consommation des voitures sur banc d'essai

Microbial Diversity and Biosignatures: An Icy Moons Perspective

The icy moons of the outer Solar System harbor potentially habitable environments for life, however, compared to the terrestrial biosphere, these environments are characterized by extremes in temperature, pressure, pH, and other physico-chemical conditions. Therefore, the search for life on these icy worlds is anchored on the study of terrestrial extreme environments (termed “analogue sites”), which harbor microorganisms at the frontiers of polyextremophily. These so-called extremophiles have been found in areas previously considered sterile: hot springs, hydrothermal vents, acidic or alkaline lakes, hypersaline environments, deep sea sediments, glaciers, and arid areas, amongst others. Such model systems and communities in extreme terrestrial environments may provide important information relevant to the astrobiology of icy bodies, including the composition of potential biological communities and the identification of biosignatures that they may produce. Extremophiles can use either sunlight (phototrophs) or chemical energy (chemotrophs) as energy sources, and different chemical compounds as electron donors or acceptors. Aerobic microorganisms use oxygen (O2) as a terminal electron acceptor, whereas anaerobic microorganisms may use nitrate (NO−3 ), sulfate (SO2−4 ), carbon dioxide (CO2), Fe(III), or other organic or inorganic molecules during respiration. The phylogenetic diversity of extremophiles is very high, leading to their broad dispersal across the phylogenetic tree of life together with a wide variety in metabolic diversity. Some metabolisms are specific to archaea, for example, methanogenesis, an anaerobic respiration during which methane (CH4) is produced. Also sulfur-reduction performed by some bacteria and archaea is considered as a primitive metabolism which is restricted to anoxic sulfur-rich habitats in nature. Methanogenesis and sulfur reduction are of specific interest for icy moon research as it might be one of the few known terrestrial metabolisms possible on these celestial bodies. Therefore, the adaptation of these intriguing microorganisms to extreme conditions will be highlighted within this review

Microbial diversity and biosignatures: an icy moons perspective

The icy moons of the outer Solar System harbor potentially habitable environments for life, however, compared to the terrestrial biosphere, these environments are characterized by extremes in temperature, pressure, pH, and other physico-chemical conditions. Therefore, the search for life on these icy worlds is anchored on the study of terrestrial extreme environments (termed \u201canalogue sites\u201d), which harbor microorganisms at the frontiers of polyextremophily. These so-called extremophiles have been found in areas previously considered sterile: hot springs, hydrothermal vents, acidic or alkaline lakes, hypersaline environments, deep sea sediments, glaciers, and arid areas, amongst others. Such model systems and communities in extreme terrestrial environments may provide important information relevant to the astrobiology of icy bodies, including the composition of potential biological communities and the identification of biosignatures that they may produce. Extremophiles can use either sunlight (phototrophs) or chemical energy (chemotrophs) as energy sources, and different chemical compounds as electron donors or acceptors. Aerobic microorganisms use oxygen (O2) as a terminal electron acceptor, whereas anaerobic microorganisms may use nitrate (NO3-), sulfate (SO42-), carbon dioxide (CO2), Fe(III), or other organic or inorganic molecules during respiration. The phylogenetic diversity of extremophiles is very high, leading to their broad dispersal across the phylogenetic tree of life together with a wide variety in metabolic diversity. Some metabolisms are specific to archaea, for example, methanogenesis, an anaerobic respiration during which methane (CH4) is produced. Also sulfur-reduction performed by some bacteria and archaea is considered as a primitive metabolism which is restricted to anoxic sulfur-rich habitats in nature. Methanogenesis and sulfur reduction are of specific interest for icy moon research as it might be one of the few known terrestrial metabolisms possible on these celestial bodies. Therefore, the adaption of these intriguing microorganisms to extreme conditions will be highlighted within this review