CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

Immunological memory is a hallmark of adaptive immunity, and understanding T cell memory will be central to the development of effective cell-mediated vaccines. The characteristics and functions of CD4 memory cells have not been well defined. Here we demonstrate that the increased size of the secondary response is solely a consequence of the increased antigen-specific precursor frequency within the memory pool. Memory cells proliferated less than primary responding cells, even within the same host. By analyzing the entry of primary and memory cells into the cell cycle, we found that the two populations proliferated similarly until day 5; after this time, fewer of the reactivated memory cells proliferated. At this time, fewer of the reactivated memory cells made IL-2 than primary responding cells, but more made IFNγ. Both these factors affected the low proliferation of the memory cells, because either exogenous IL-2 or inhibition of IFNγ increased the proliferation of the memory cells

Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines - Exploratory Analyses within a Randomised Controlled Trial

Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.peer-reviewe

TMS-induced Neural Noise in Sensory Cortex Interferes with Short-term Memory Storage in Prefrontal Cortex

In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.\u27s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature

The Relationship between Working Memory and Cognitive Functioning in Children

One-hundred and forty-four Year 1 children (51% boys and 49% girls, mean age 6) from Queensland State primary schools participated in a study to investigate the relationship between working memory and cognitive functioning. Children were given two tests of cognitive functioning (the School-Years Screening Test for the Evaluation of Mental Status (SYSTEMS) and the Kaufman Brief Intelligence Test (K-BIT)) and six subtests of working memory from the Working Memory Test Battery for Children (WMTB-C) (Backward Digit Recall, Listening Recall, Digit Recall, Word List Matching, Word List Recall and Non-word List Recall). The two cognitive tests correlated at r = .50. Results showed a high correlation between SYSTEMS and the Phonological Loop (PL) component of working memory. The K-BIT also correlated highly with PL component. The SYSTEMS and K-BIT showed various levels of correlation with the working memory sub-tests. A measurement model utilising Confirmatory Factor Analysis method showed a strong relationship between working memory and cognitive functioning, the degree of fit for the model was very high at GFI = .996

Adjusting process count on demand for petascale global optimization⋆

There are many challenges that need to be met before efficient and reliable computation at the petascale is possible. Many scientific and engineering codes running at the petascale are likely to be memory intensive, which makes thrashing a serious problem for many petascale applications. One way to overcome this challenge is to use a dynamic number of processes, so that the total amount of memory available for the computation can be increased on demand. This paper describes modifications made to the massively parallel global optimization code pVTdirect in order to allow for a dynamic number of processes. In particular, the modified version of the code monitors memory use and spawns new processes if the amount of available memory is determined to be insufficient. The primary design challenges are discussed, and performance results are presented and analyzed

Linear-Space Approximate Distance Oracles for Planar, Bounded-Genus, and Minor-Free Graphs

A (1 + eps)-approximate distance oracle for a graph is a data structure that supports approximate point-to-point shortest-path-distance queries. The most relevant measures for a distance-oracle construction are: space, query time, and preprocessing time. There are strong distance-oracle constructions known for planar graphs (Thorup, JACM'04) and, subsequently, minor-excluded graphs (Abraham and Gavoille, PODC'06). However, these require Omega(eps^{-1} n lg n) space for n-node graphs. We argue that a very low space requirement is essential. Since modern computer architectures involve hierarchical memory (caches, primary memory, secondary memory), a high memory requirement in effect may greatly increase the actual running time. Moreover, we would like data structures that can be deployed on small mobile devices, such as handhelds, which have relatively small primary memory. In this paper, for planar graphs, bounded-genus graphs, and minor-excluded graphs we give distance-oracle constructions that require only O(n) space. The big O hides only a fixed constant, independent of \epsilon and independent of genus or size of an excluded minor. The preprocessing times for our distance oracle are also faster than those for the previously known constructions. For planar graphs, the preprocessing time is O(n lg^2 n). However, our constructions have slower query times. For planar graphs, the query time is O(eps^{-2} lg^2 n). For our linear-space results, we can in fact ensure, for any delta > 0, that the space required is only 1 + delta times the space required just to represent the graph itself

The hippocampus, prefrontal cortex, and perirhinal cortex are critical to incidental order memory.

Considerable research in rodents and humans indicates the hippocampus and prefrontal cortex are essential for remembering temporal relationships among stimuli, and accumulating evidence suggests the perirhinal cortex may also be involved. However, experimental parameters differ substantially across studies, which limits our ability to fully understand the fundamental contributions of these structures. In fact, previous studies vary in the type of temporal memory they emphasize (e.g., order, sequence, or separation in time), the stimuli and responses they use (e.g., trial-unique or repeated sequences, and incidental or rewarded behavior), and the degree to which they control for potential confounding factors (e.g., primary and recency effects, or order memory deficits secondary to item memory impairments). To help integrate these findings, we developed a new paradigm testing incidental memory for trial-unique series of events, and concurrently assessed order and item memory in animals with damage to the hippocampus, prefrontal cortex, or perirhinal cortex. We found that this new approach led to robust order and item memory, and that hippocampal, prefrontal and perirhinal damage selectively impaired order memory. These findings suggest the hippocampus, prefrontal cortex and perirhinal cortex are part of a broad network of structures essential for incidentally learning the order of events in episodic memory