Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

Correlates of loneliness among university students

Background The purpose of this study was to investigate level of loneliness, essential needs during university education, and relationships between loneliness, essential needs, and characteristics of university students. A sample comprising 721 students participated in the study. The mean age was 21.58 (SD = 1.73) with a range from 18 to 25. The majority of the students were female (70.6%) and were living in students' dormitory (67.5%) with low (87.8%) income, away from their parents. Methods The UCLA-R loneliness scale and sociodemographic questionnaire which includes an open-ended question on essential needs during university education were administered. Pearson-Product-Moment correlations were used to explore the relationships between participants' loneliness, needs, and characteristics. Results It was found that 60.2% of the participants experienced loneliness. Economical support (81.6%), social interaction (46.9%) and psychosocial support (35%) were the essential needs during university education reported by the participants. The study findings indicate that there were significant relationships between the needs of economical support, social interaction, and loneliness level of university students. Results also show that there were significant relationships among romantic relationship, parents' status and loneliness. Participants' loneliness levels were relatively higher who had not any romantic relationship and were not from married families. Conclusion The findings of this study provided essential information, about Turkish university students, concerning: level of loneliness and relationships that exist among loneliness, needs and sociodemographic characteristics. The findings also suggest implications for psychosocial practice. Because of the mean of loneliness were found to be high (45.49 ± 10.07), for this study, professionals need to pay attention to Turkish university students' psychosocial state, and need to empower them in establishing social relations

Relative Necessity Reformulated

This paper discusses some serious difficulties for what we shall call the standard account of various kinds of relative necessity, according to which any given kind of relative necessity may be defined by a strict conditional - necessarily, if C then p - where C is a suitable constant proposition, such as a conjunction of physical laws. We argue, with the help of Humberstone (1981), that the standard account has several unpalatable consequences. We argue that Humberstone's alternative account has certain disadvantages, and offer another - considerably simpler - solution

FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections

Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit

Variance and Autocorrelation of the Spontaneous Slow Brain Activity

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r1 values, which enables a better understanding of the network changes related to various brain diseases

Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection

The effects of a partitioned var gene repertoire of Plasmodium falciparum on antigenic diversity and the acquisition of clinical immunity

<p>Abstract</p> <p>Background</p> <p>The human malaria parasite <it>Plasmodium falciparum </it>exploits antigenic diversity and within-host antigenic variation to evade the host's immune system. Of particular importance are the highly polymorphic <it>var </it>genes that encode the family of cell surface antigens PfEMP1 (<it>Plasmodium falciparum </it>Erythrocyte Membrane Protein 1). It has recently been shown that in spite of their extreme diversity, however, these genes fall into distinct groups according to chromosomal location or sequence similarity, and that recombination may be confined within these groups.</p> <p>Methods</p> <p>This study presents a mathematical analysis of how recombination hierarchies affect diversity, and, by using simple stochastic simulations, investigates how intra- and inter-genic diversity influence the rate at which individuals acquire clinical immunity.</p> <p>Results</p> <p>The analysis demonstrates that the partitioning of the <it>var </it>gene repertoire has a limiting effect on the total diversity attainable through recombination and that the limiting effect is strongly influenced by the respective sizes of each of the partitions. Furthermore, by associating expression of one of the groups with severe malaria it is demonstrated how a small number of infections can be sufficient to protect against disease despite a seemingly limitless number of possible non-identical repertoires.</p> <p>Conclusion</p> <p>Recombination hierarchies within the <it>var </it>gene repertoire of <it>P. falciparum </it>have a severe effect on strain diversity and the process of acquiring immunity against clinical malaria. Future studies will show how the existence of these recombining groups can offer an evolutionary advantage in spite of their restriction on diversity.</p