Platelet-activating factor and hyperacute rejection: The effect of a platelet-activating factor antagonist, sri 63-441, on rejection of xenografts and allografts in sensitized hosts

The pathogenesis of hyperacute transplantation reactions includes the activation of a cascade of nonspecific inflammatory reactions that precipitates the destruction of the target organ. Platelet-activating factor (PAF) represents an important component of these inflammatory cascades, and we have examined the influence of a specific PAF receptor antagonist (SRI 63-441) on the inhibition of hyperacute rejection in two experimental models, the rejection of rat cardiac allografts by presensitized recipients and guinea pig-to-rat and mouse-to- rat cardiac xenografts. Our results demonstrate that inhibition of PAF function by SRI 63-441 has a variable effect on the survival of cardiac allografts in presensitized rat recipients. In the ACI to sensitized BN cardiac allograft model, the use of SRI 63-441 alone, or in combination with CsA, FK506, or prostaglandin E2(PGE2), does not prolong graft survival. As we have previously reported, SRI 63-441 does act as a single agent to prolong the survival of ACI to sensitized LEW grafts, and this survival effect is synergistic when combined with CsA. Here we extend these results to demonstrate that this survival is also extended when FK506 is used in the ACI-to-LEW model. Concordant mouse-to- rat cardiac xenografts are also relatively resistant to prolongation of graft survival following treatment with SRI 63-441 alone or in combination with CsA or FK506. Discordant xenografts appear to be more susceptible to inhibition of the rejection reaction with SRI 63-441. When either donor or recipient animals were treated with SRI 63-441 alone, or in combination with CsA or FK506, there was significant prolongation of guinea pig-to-rat cardiac xenograft survival. These results are consistent with our earlier description of the effectiveness of SRI 63-441 in preventing the rejection of cat- to-rabbit kidney xenografts. We believe that these resuits demonstrate that the use of the SRI 63-441 to specifically interfere with the function of PAF has the effect of prolonging graft survival in those systems in which preformed antibody and/or complement activation are important components of the hyperacute reaction. This synthetic drug is representative of a family of compounds whose structure can be modified to balance their therapeutic and toxicity activities, and may prove to be important components of a polytherapeutic approach to the control of graft rejection in sensitized patients or following discordant xenografting. © 1990 by Williams and Wilkins

Attentional differences in a driving hazard perception task in adults with autism spectrum disorders

The current study explored attentional processing of social and non social stimuli in ASD within the context of a driving hazard perception task. Participants watched videos of road scenes and detected hazards while their eye movements were recorded. Although individuals with ASD demonstrated relatively good detection of driving hazards, they were slower to orient to hazards. Greater attentional capture in the time preceding the hazards’ onset was associated with lower verbal IQ. The findings suggest that individuals with ASD may distribute and direct their attention diferently when identifying driving hazards

An efficient record linkage scheme using graphical analysis for identifier error detection

Integration of information on individuals (record linkage) is a key problem in healthcare delivery, epidemiology, and "business intelligence" applications. It is now common to be required to link very large numbers of records, often containing various combinations of theoretically unique identifiers, such as NHS numbers, which are both incomplete and error-prone

Atmospheric Evolution

Earth's atmosphere has evolved as volatile species cycle between the atmosphere, ocean, biomass and the solid Earth. The geochemical, biological and astrophysical processes that control atmospheric evolution are reviewed from an "Earth Systems" perspective, with a view not only to understanding the history of Earth, but also to generalizing to other solar system planets and exoplanets.Comment: 34 pages, 3 figures, 2 tables. Accepted as a chapter in "Encyclopaedia of Geochemistry", Editor Bill White, Springer-Nature, 201

TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage

RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions. Conversely, accumulation of TRAIP is normal in RAP80-depleted cells, implying that TRAIP acts upstream of RAP80 recruitment to DNA lesions. TRAIP localizes to sites of DNA damage and cells lacking TRAIP exhibit classical DNA-damage response-defect phenotypes. Biochemical analysis reveals that the N terminus of TRAIP is crucial for RAP80 interaction, while the C terminus of TRAIP is required for TRAIP localization to sites of DNA damage through a direct interaction with RNF20-RNF40. Taken together, our findings demonstrate that the novel RAP80-binding partner TRAIP regulates recruitment of the damage signalling machinery and promotes homologous recombinationopen

A change in the transportation needs today, a better future for tomorrow – climate change review

No sooner than later, the world will be living hell as a result of the transportation effects on our climate now escalating. The pressure is now growing towards their resultant effects to be totally eradicated in order to save our planet otherwise, the stabilisation of these effects; global warming, greenhouse gas (GHG) emission and degradation will need to be sought after. The world all over is at it now in an effort to restore our climate, to save it from the effects of these catastrophes/disasters. On the proposition of the Kyoto Protocol in1997, the main focus was to decrease greenhouse emissions of mainly six gases – Carbon dioxide, methane, nitrous oxide, sulphur hexafluoride, Hydro fluorocarbons (HFCs) and Per fluorinated Compounds (PFCs). And transport alone, accounts for over 26% of global CO2 and has been regarded as one of the few industrial sectors wherein emissions are still on the increase, on this basis, researchers and policy makers are all at it to tackle the menace of climate changes through provision of sustainable transport. This paper focuses on the new and developed technologies like the renewable energy source [RES], which will be an alternative to transport fuels to avoid the dependence on petroleum which after effects are damaging to the world climate, and may probably not be there forever to continue serving the world ever increasing population. While the long term solutions are being sought, these alternatives will make do for now

Human–agent collaboration for disaster response

In the aftermath of major disasters, first responders are typically overwhelmed with large numbers of, spatially distributed, search and rescue tasks, each with their own requirements. Moreover, responders have to operate in highly uncertain and dynamic environments where new tasks may appear and hazards may be spreading across the disaster space. Hence, rescue missions may need to be re-planned as new information comes in, tasks are completed, or new hazards are discovered. Finding an optimal allocation of resources to complete all the tasks is a major computational challenge. In this paper, we use decision theoretic techniques to solve the task allocation problem posed by emergency response planning and then deploy our solution as part of an agent-based planning tool in real-world field trials. By so doing, we are able to study the interactional issues that arise when humans are guided by an agent. Specifically, we develop an algorithm, based on a multi-agent Markov decision process representation of the task allocation problem and show that it outperforms standard baseline solutions. We then integrate the algorithm into a planning agent that responds to requests for tasks from participants in a mixed-reality location-based game, called AtomicOrchid, that simulates disaster response settings in the real-world. We then run a number of trials of our planning agent and compare it against a purely human driven system. Our analysis of these trials show that human commanders adapt to the planning agent by taking on a more supervisory role and that, by providing humans with the flexibility of requesting plans from the agent, allows them to perform more tasks more efficiently than using purely human interactions to allocate tasks. We also discuss how such flexibility could lead to poor performance if left unchecked