Measuring chess experts' single-use sequence knowledge: an archival study of departure from 'theoretical' openings

The respective roles of knowledge and search have received considerable attention in the literature on expertise. However, most of the evidence on knowledge has been indirect--e.g., by inferring the presence of chunks in long-term memory from performance in memory recall tasks. Here we provide direct estimates of the amount of monochrestic (single use) and rote knowledge held by chess players of varying skill levels. From a large chess database, we analyzed 76,562 games played in 2008 by individuals ranging from Class B players (average players) to Masters to measure the extent to which players deviate from previously known initial sequences of moves ("openings"). Substantial differences were found in the number of moves known by players of different skill levels, with more expert players knowing more moves. Combined with assumptions independently made about the branching factor in master games, we estimate that masters have memorized about 100,000 opening moves. Our results support the hypothesis that monochrestic knowledge is essential for reaching high levels of expertise in chess. They provide a direct, quantitative estimate of the number of opening moves that players have to know to reach master level.     

Episodic therapy for genital herpes in sub-saharan Africa: a pooled analysis from three randomized controlled trials

Background

A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.

Methodology/Principal Findings

Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm²), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.

Conclusions/Significance

There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing.     

Multi-channel data collection and visualization system for intramyocardial electrograms]

The aim of the project was to develop a multichannel data acquisition system for the recording and visualisation of intramyocardial electrograms (IEGM) from both the spontaneously beating and the artificially paced heart. Signal processing comprises multi-step amplification, filtering (0.05-800 Hz), and AD conversion (12 Bit max. 6.25 kHz). IEGMs can be obtained either in unipolar or bipolar mode. Stimulation of the heart is achieved by an incorporated programmable dual-chamber pacemaker that can be selectively switched to the input channels. A LabView-based graphical user interface permits the programming of all system parameters via a microcontroller, and supports data acquisition and visualisation. The system can be used in animal experiments to monitor the spread of excitation across the heart, to measure propagation velocity, or to measure the impact of drugs and pathological changes on the morphology of IEGMs.     

Structural dynamics of alpha-actinin-vinculin interactions

Alpha-actinin and vinculin orchestrate reorganization of the actin cytoskeleton following the formation of adhesion junctions. alpha-Actinin interacts with vinculin through the binding of an alpha-helix (alphaVBS) present within the R4 spectrin repeat of its central rod domain to vinculin's N-terminal seven-helical bundle domain (Vh1). The Vh1:alphaVBS structure suggests that alphaVBS first unravels from its buried location in the triple-helical R4 repeat to allow it to bind to vinculin. alphaVBS binding then induces novel conformational changes in the N-terminal helical bundle of Vh1, which disrupt its intramolecular association with vinculin's tail domain and which differ from the alterations in Vh1 provoked by the binding of talin. Surprisingly, alphaVBS binds to Vh1 in an inverted orientation compared to the binding of talin's VBSs to vinculin. Importantly, the binding of alphaVBS and talin's VBSs to vinculin's Vh1 domain appear to also trigger distinct conformational changes in full-length vinculin, opening up distant regions that are buried in the inactive molecule. The data suggest a model where vinculin's Vh1 domain acts as a molecular switch that undergoes distinct structural changes provoked by talin and alpha-actinin binding in focal adhesions versus adherens junctions, respectively.     

Regulation of matrix metalloproteinase (MMP) activity by the low-density lipoprotein receptor-related protein (LRP). A new function for an "old friend"

Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected toxicity and new targets are thus eagerly awaited. The identification of endocytic clearance of several MMPs by the low-density lipoprotein receptor-related protein (LRP) might provide insight into novel strategies for controlling MMP level during malignant processes. This review attempts to summarize recent aspects on the cellular and molecular basis of LRP-mediated endocytic disposal of MMPs.     

Beneficial and detrimental influences of tissue inhibitor of metalloproteinase-1 (TIMP-1) in tumor progression

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is one representative of the natural matrix metalloproteinase (MMP) inhibitor family, encompassing four members. It inhibits all MMPs, except several MT-MMPs, and a disintegrin with a metalloproteinase domain (ADAM)-10 with Kis < nM. Unexpectedly, its upregulation was associated to poor clinical outcome for several cancer varieties. Such finding might be related to the growth-promoting and survival activities of TIMP-1 for normal and cancer cells. In most cases, such properties are MMP-independent and binding of TIMP-1 to an unknown receptor system can trigger JAK (or FAK)/PI3 kinase/Akt/bad-bclX2 (erythroid, myeloid, epithelial cell lines) or Ras/Raf1/FAK (osteosarcoma cell line) signaling pathways. The relationship between viral infection and TIMP-1 expression is here underlined. Thus, TIMP-1 might display a dual influence on tumor progression; either beneficial by inhibiting MMPs as MMP-9 and by impairing angiogenesis or detrimental by favoring cancer cells growth or survival. We consider that the proMMP-9/TIMP-1 balance is of critical importance in early events of tumor progression, and might show promise as diagnostic and prognostic marker of malignancy.     

Phenotypic plasticity of growth trajectory and ontogenic allometry in response to density for eucalyptus hybrid clones and families

BACKGROUND: and Aims Response to density is a crucial aspect of the ecology of trees in forests and plantations. Few studies have investigated the genetics of plasticity in response to density for growth traits such as height and circumference through development. METHODS: Two experiments were carried out in the field, the first with full-sib families of Eucalyptus urophylla x E. grandis hybrids, and the second with clones of E. tereticornis x E. grandis hybrids planted across a range of densities (625, 1111 and 2500 trees ha-1). Height, circumference and stem taper were measured through development in both experiments. Variance components were estimated and a repeated measure approach for plasticity and three different methods were used to compare the variance-covariance matrix across densities. KEY RESULTS: Genetic variance was significantly different from zero but the density x genotype interaction was significant only for clone experiments at the adult stage. Significant plasticity for three traits in both experiments was found. In the clone experiments, a significant clone x time x density interaction was found, suggesting that plasticity for growth and stem form is under genetic control. In both experiments, density did not affect environmental correlation, which remained high throughout tree development. The impact of density on genetic correlation was marked in the clone experiment, with a reduced value at lower density, but was not observed in the family trial. The differences between clones and family are mainly explained by the distribution of genetic variation within and among genotypes. CONCLUSIONS: The results suggest that plasticity for growth traits and form of tropical Eucalyptus species is under genetic control and that the environment changes genetic co-variation through ontogeny. The findings confirm that a tree population with a narrow genetic basis (represented by clones) is sensitive to a changing environment, whereas a population with a broader genetic basis (full-sib family here) exhibits a more stable reaction.