Generation of CTL responses using Kunjin replicon RNA

The Kunjin replicon was used to express a polytope that consisted of seven hepatitis C virus cytotoxic T lymphocyte epitopes and one influenza cytotoxic T lymphocyte epitope for vaccination studies. The self-replicating nature of, and expression from, the ribonucleic acid was confirmed in vitro . Initial vaccinations with one dose of Kun-Poly ribonucleic acid showed that an influenza-specific cytotoxic T lymphocyte response was elicited more efficiently by intradermal inoculation compared with intramuscular delivery. Two micrograms of ribonucleic acid delivered in the ear pinnae of mice was sufficient to elicit a detectable cytotoxic T lymphocyte response 10 days post-vaccination. Further vaccination studies showed that four of the seven hepatitis C virus cytotoxic T lymphocyte epitopes were able to elicit weak cytotoxic T lymphocyte responses whereas the influenza epitope was able to elicit strong, specific cytotoxic T lymphocyte responses following three doses of Kun-Poly ribonucleic acid. These studies vindicate the use of the Kunjin replicon as a vector to deliver encoded proteins for the development of cell-mediated immune responses.

Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype

Multiple HLA class I alleles can bind peptides with common sequence motifs due to structural similarities in the peptide binding cleft, and these groups of alleles have been classified into supertypes. Nine major HLA supertypes have been proposed, including an A24 supertype that includes A*2301, A*2402, and A*3001. Evidence for this A24 supertype is limited to HLA sequence homology and/or similarity in peptide binding motifs for the alleles. To investigate the immunological relevance of this proposed supertype, we have examined two viral epitopes (from EBV and CMV) initially defined as HLA-A*2301-binding peptides. The data clearly demonstrate that each peptide could be recognized by CTL clones in the context of A*2301 or A*2402; thus validating the inclusion of these three alleles within an A24 supertype. Furthermore, CTL responses to the EBV epitope were detectable in both A*2301(+) and A*2402(+) individuals who had been previously exposed to this virus. These data substantiate the biological relevance of the A24 supertype, and the identification of viral epitopes with the capacity to bind promiscuously across this supertype could aid efforts to develop CTL-based vaccines or immunotherapy. The degeneracy in HLA restriction displayed by some T cells in this study also suggests that the dogma of self-MHC restriction needs some refinement to accommodate foreign peptide recognition in the context of multiple supertype alleles.

Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick

Passive avoidance learning is with advantage studied in day-old chicks trained to distinguish between beads of two different colors, of which one at training was associated with aversive taste. During the first 30-min post-training, two periods of glutamate release occur in the forebrain. One period is immediately after the aversive experience, when glutamate release is confined to the left hemisphere. A second release, 30 min later, may be bilateral, perhaps with preponderance of the right hemisphere. The present study showed increased pool sizes of glutamate and glutamine, specifically in the left hemisphere, at the time when the first glutamate release occurs, indicating de novo synthesis of glutamate/glutamine from glucose or glycogen, which are the only possible substrates. Behavioral evidence that memory is extinguished by intracranial administration at this time of iodoacetate, an inhibitor of glycolysis and glycogenolysis, and that the extinction of memory is counteracted by injection of glutamine, supports this concept. A decrease in forebrain glycogen of similar magnitude and coinciding with the increase in glutamate and glutamine suggests that glycogen rather than glucose is the main source of newly synthesized glutamate/glutamine. The second activation of glutamatergic activity 30 min after training, when memory is consolidated into stable, long-term memory, is associated with a bilateral increase in pool size of glutamate/glutamine. No glycogenolysis was observed at this time, but again there is a temporal correlation with sensitivity to inhibition by iodoacetate and rescue by glutamine, indicating the importance of de novo synthesis of glutamate/glutamine from glucose or glycogen. (C) 2003 Elsevier B.V All rights reserved.

Cognitive intervention protocol for age-related memory impairments

With the number of elderly people increasing tremendously worldwide, comes the need for effective methods to maintain or improve older adults' cognitive performance. Using continuous neurofeedback, through the use of EEG techniques, people can learn how to train and alter their brain electrical activity. A software platform that puts together the proposed rehabilitation methodology has been developed: a digital game protocol that supports neurofeedback training of alpha and theta rhythms, by reading the EEG activity and presenting it back to the subject, interleaved with neurocognitive tasks such as n-Back and Corsi Block-Tapping. This tool will be used as a potential rehabilitative platform for age-related memory impairments.

Memory as discourse in Harold Pinter's old times, betrayal and a kind of Alaska

This paper aims at developing the topic of identity and the narration of the self through the other in Harold Pinter’s plays Old Times, Betrayal and A Kind of Alaska. In these plays Pinter deploys strategies to convey multiple implications which are based on the power of memory in which the structure of the plays is concocted.

The Past, Polish politics of memory, and stereotyping: an intercultural perspective

The main idea of the article is to consider the interdependence between Politics of Memory (as a type of narrating the Past) and Stereotyping. The author suggests that, in a time of information revolution, we are still constructing images of others on the basis of simplification, overestimation of association between features, and illusory correlations, instead of basing them on knowledge and personal contact. The Politics of Memory, national remembrance, and the historical consciousness play a significant role in these processes, because – as the author argues – they transform historically based 'symbolic analogies' into 'illusory correlations' between national identity and the behavior of its members. To support his theoretical investigation, the author presents results of his draft experiment and two case studies: (a) a social construction of images of neighbors based on Polish narrations about the Past; and (b) various processes of stereotyping based on the Remembrance of the Holocaust. All these considerations lead him to state that the Politics of Memory should be recognized as an influential source of commonly shared stereotypes on other cultures and nations.

Runtime Elision of Transactional Barriers for Captured Memory

In this paper, we propose a new technique that can identify transaction-local memory (i.e. captured memory), in managed environments, while having a low runtime overhead. We implemented our proposal in a well known STM framework (Deuce) and we tested it in STMBench7 with two different STMs: TL2 and LSA. In both STMs the performance improved significantly (4 times and 2.6 times, respectively). Moreover, running the STAMP benchmarks with our approach shows improvements of 7 times in the best case for the Vacation application.

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 µ/L and it was completely eliminated after 96 h.

Software transactional memory as a building block for parallel embedded realtime systems

The recent trends of chip architectures with higher number of heterogeneous cores, and non-uniform memory/non-coherent caches, brings renewed attention to the use of Software Transactional Memory (STM) as a fundamental building block for developing parallel applications. Nevertheless, although STM promises to ease concurrent and parallel software development, it relies on the possibility of aborting conflicting transactions to maintain data consistency, which impacts on the responsiveness and timing guarantees required by embedded real-time systems. In these systems, contention delays must be (efficiently) limited so that the response times of tasks executing transactions are upper-bounded and task sets can be feasibly scheduled. In this paper we assess the use of STM in the development of embedded real-time software, defending that the amount of contention can be reduced if read-only transactions access recent consistent data snapshots, progressing in a wait-free manner. We show how the required number of versions of a shared object can be calculated for a set of tasks. We also outline an algorithm to manage conflicts between update transactions that prevents starvation.

WCET analysis considering contention on memory bus in COTS-based multicores

The usage of COTS-based multicores is becoming widespread in the field of embedded systems. Providing realtime guarantees at design-time is a pre-requisite to deploy real-time systems on these multicores. This necessitates the consideration of the impact of the contention due to shared low-level hardware resources on the Worst-Case Execution Time (WCET) of the tasks. As a step towards this aim, this paper first identifies the different factors that make the WCET analysis a challenging problem in a typical COTS-based multicore system. Then, we propose and prove, a mathematically correct method to determine tight upper bounds on the WCET of the tasks, when they are co-scheduled on different cores.

Response time analysis of COTS-Based multicores considering the contention on the shared memory bus

The current industry trend is towards using Commercially available Off-The-Shelf (COTS) based multicores for developing real time embedded systems, as opposed to the usage of custom-made hardware. In typical implementation of such COTS-based multicores, multiple cores access the main memory via a shared bus. This often leads to contention on this shared channel, which results in an increase of the response time of the tasks. Analyzing this increased response time, considering the contention on the shared bus, is challenging on COTS-based systems mainly because bus arbitration protocols are often undocumented and the exact instants at which the shared bus is accessed by tasks are not explicitly controlled by the operating system scheduler; they are instead a result of cache misses. This paper makes three contributions towards analyzing tasks scheduled on COTS-based multicores. Firstly, we describe a method to model the memory access patterns of a task. Secondly, we apply this model to analyze the worst case response time for a set of tasks. Although the required parameters to obtain the request profile can be obtained by static analysis, we provide an alternative method to experimentally obtain them by using performance monitoring counters (PMCs). We also compare our work against an existing approach and show that our approach outperforms it by providing tighter upper-bound on the number of bus requests generated by a task.

Finding an upper bound on the increase in execution time due to contention on the memory bus in COTS-based multicore systems

Contention on the memory bus in COTS based multicore systems is becoming a major determining factor of the execution time of a task. Analyzing this extra execution time is non-trivial because (i) bus arbitration protocols in such systems are often undocumented and (ii) the times when the memory bus is requested to be used are not explicitly controlled by the operating system scheduler; they are instead a result of cache misses. We present a method for finding an upper bound on the extra execution time of a task due to contention on the memory bus in COTS based multicore systems. This method makes no assumptions on the bus arbitration protocol (other than assuming that it is work-conserving).