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Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen.
Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor-bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors
Planning with Information-Processing Constraints and Model Uncertainty in Markov Decision Processes
Information-theoretic principles for learning and acting have been proposed
to solve particular classes of Markov Decision Problems. Mathematically, such
approaches are governed by a variational free energy principle and allow
solving MDP planning problems with information-processing constraints expressed
in terms of a Kullback-Leibler divergence with respect to a reference
distribution. Here we consider a generalization of such MDP planners by taking
model uncertainty into account. As model uncertainty can also be formalized as
an information-processing constraint, we can derive a unified solution from a
single generalized variational principle. We provide a generalized value
iteration scheme together with a convergence proof. As limit cases, this
generalized scheme includes standard value iteration with a known model,
Bayesian MDP planning, and robust planning. We demonstrate the benefits of this
approach in a grid world simulation.Comment: 16 pages, 3 figure
Total humerus replacement for osteosarcoma with proximal part of humerus: a case report
Incisional biopsy and intramedullary pinning were performed for pathological fracture associated with a malignant bone tumor of the proximal humerus. Osteosarcoma, for which preoperative chemotherapy had been performed, was confirmed by postoperative pathological examination. To achieve wide resection and acquire a safe resected margin, total humerus replacement was performed, and the whole humerus was reconstructed using the Howmedica Modular Reconstruction system. The patient resumed normal activities, although mild contracture of the elbow joint remains 8 years after surgery
Anomalous Experiences and Paranormal Attributions: Psychometric Challenges in Studying Their Measurement and Relationship
© 2019 American Psychological Association. Research on the psychology of paranormal, religious, and delusional belief has been stifled by a lack of careful distinction between anomalous experiences and their corresponding attributions. The Survey of Anomalous Experience (SAE; Irwin, Dagnall, & Drinkwater, 2013) addresses this nuance by measuring proneness to anomalous experience (PAE) and proneness to paranormal attribution (PPA). Using data (351 men, 1,026 women) from 7 previously published studies, we examined the SAE's internal validity via Rasch scaling and differential item functioning analyses. PPA showed good Rasch model fit and no item bias, but it lacked adequate reliability. Several PAE items showed misfit to the Rasch model or gender bias, though deleting 5 items produced a scale with acceptable reliability. Finally, we failed to validate a 3-category rating scale version with the goal of improving the SAE's psychometric properties. All 3 formulations revealed a secondary factor related to the items' extremity rather than contents, suggesting that future research should consider the intensity of respondents' anomalous experiences and paranormal attributions
Integration of Catalysis with Storage for the Design of Multi-Electron Photochemistry Devices for Solar Fuel
Decarbonization of the transport system and a transition to a new diversified energy system that is scalable and sustainable, requires a widespread implementation of carbon-neutral fuels. In biomimetic supramolecular nanoreactors for solar-to-fuel conversion, water-splitting catalysts can be coupled to photochemical units to form complex electrochemical nanostructures, based on a systems integration approach and guided by magnetic resonance knowledge of the operating principles of biological photosynthesis, to bridge between long-distance energy transfer on the short time scale of fluorescence, ~10−9 s, and short-distance proton-coupled electron transfer and storage on the much longer time scale of catalysis, ~10−3 s. A modular approach allows for the design of nanostructured optimized topologies with a tunneling bridge for the integration of storage with catalysis and optimization of proton chemical potentials, to mimic proton-coupled electron transfer processes in photosystem II and hydrogenase
Simulating radiation damage cascades in graphite
Molecular dynamics simulation is used to study radiation damage cascades in graphite. High statistical precision is obtained by sampling a wide energy range (100–2500 eV) and a large number of initial directions of the primary knock-on atom. Chemical bonding is described using the Environment Dependent Interaction Potential for carbon. Graphite is found to exhibit a radiation response distinct from metals and oxides primarily due to the absence of a thermal spike which results in point defects and disconnected regions of damage. Other unique attributes include exceedingly short cascade lifetimes and fractal-like atomic trajectories. Unusually for a solid, the binary collision approximation is useful across a wide energy range, and as a consequence residual damage is consistent with the Kinchin–Pease model. The simulations are in agreement with known experimental data and help to clarify substantial uncertainty in the literature regarding the extent of the cascade and the associated damage
Sri Lankan tsunami refugees: a cross sectional study of the relationships between housing conditions and self-reported health
BACKGROUND: On the 26th December 2004 the Asian tsunami devastated the Sri Lankan coastline. More than two years later, over 14,500 families were still living in transitional shelters. This study compares the health of the internally displaced people (IDP), living in transitional camps with those in permanent housing projects provided by government and non-government organisations in Sri Lanka. METHODS: This study was conducted in seven transitional camps and five permanent housing projects in the south west of Sri Lanka. Using an interviewer-led questionnaire, data on the IDPs' self-reported health and housing conditions were collected from 154 participants from transitional camps and 147 participants from permanent housing projects. Simple tabulation with non-parametric tests and logistic regression were used to identify and analyse relationships between housing conditions and the reported prevalence of specific symptoms. RESULTS: Analysis showed that living conditions were significantly worse in transitional camps than in permanent housing projects for all factors investigated, except 'having a leaking roof'. Transitional camp participants scored significantly lower on self-perceived overall health scores than those living in housing projects. After controlling for gender, age and marital status, living in a transitional camp compared to a housing project was found to be a significant risk factor for the following symptoms; coughs OR: 3.53 (CI: 2.11-5.89), stomach ache 4.82 (2.19-10.82), headache 5.20 (3.09-8.76), general aches and pains 6.44 (3.67-11.33) and feeling generally unwell 2.28 (2.51-7.29). Within transitional camp data, the only condition shown to be a significant risk factor for any symptom was household population density, which increased the risk of stomach aches 1.40 (1.09-1.79) and headaches 1.33 (1.01-1.77). CONCLUSION: Internally displaced people living in transitional camps are a vulnerable population and specific interventions need to be targeted at this population to address the health inequalities that they report to be experiencing. Further studies need to be conducted to establish which aspects of their housing environment predispose them to poorer health
Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands
"© 2015 Gonzalez et al. 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"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)
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