Development of a thermodynamics of human cognition and human culture.

Inspired by foundational studies in classical and quantum physics, and by information retrieval studies in quantum information theory, we prove that the notions of 'energy' and 'entropy' can be consistently introduced in human language and, more generally, in human culture. More explicitly, if energy is attributed to words according to their frequency of appearance in a text, then the ensuing energy levels are distributed non-classically, namely, they obey Bose-Einstein, rather than Maxwell-Boltzmann, statistics, as a consequence of the genuinely 'quantum indistinguishability' of the words that appear in the text. Secondly, the 'quantum entanglement' due to the way meaning is carried by a text reduces the (von Neumann) entropy of the words that appear in the text, a behaviour which cannot be explained within classical (thermodynamic or information) entropy. We claim here that this 'quantum-type behaviour is valid in general in human language', namely, any text is conceptually more concrete than the words composing it, which entails that the entropy of the overall text decreases. In addition, we provide examples taken from cognition, where quantization of energy appears in categorical perception, and from culture, where entities collaborate, thus 'entangle', to decrease overall entropy. We use these findings to propose the development of a new 'non-classical thermodynamic theory' for human cognition, which also covers broad parts of human culture and its artefacts and bridges concepts with quantum physics entities. This article is part of the theme issue 'Thermodynamics 2.0: Bridging the natural and social sciences (Part 2)'.

New fundamental evidence of non-classical structure in the combination of natural concepts.

We recently performed cognitive experiments on conjunctions and negations of two concepts with the aim of investigating the combination problem of concepts. Our experiments confirmed the deviations (conceptual vagueness, underextension, overextension etc.) from the rules of classical (fuzzy) logic and probability theory observed by several scholars in concept theory, while our data were successfully modelled in a quantum-theoretic framework developed by ourselves. In this paper, we isolate a new, very stable and systematic pattern of violation of classicality that occurs in concept combinations. In addition, the strength and regularity of this non-classical effect leads us to believe that it occurs at a more fundamental level than the deviations observed up to now. It is our opinion that we have identified a deep non-classical mechanism determining not only how concepts are combined but, rather, how they are formed. We show that this effect can be faithfully modelled in a two-sector Fock space structure, and that it can be exactly explained by assuming that human thought is the superposition of two processes, a 'logical reasoning', guided by 'logic', and a 'conceptual reasoning', guided by 'emergence', and that the latter generally prevails over the former. All these findings provide new fundamental support to our quantum-theoretic approach to human cognition.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Quantification of the influence of trimethylamine-N-oxide (TMAO) on the heat resistance of Escherichia coli K12 at lethal temperatures.

AIM: To quantify the influence of trimethylamine-N-oxide (TMAO) on the heat resistance of Escherichia coli K12 MG1655 cells at static temperatures. METHODS AND RESULTS: Stationary-phase E. coli cells were inactivated at 52, 54 and 58°C. The heat resistance is described as reduction in the inactivation rate, k(max) , and/or an increase in the time for one decimal reduction, D, and/or an increase in the time for the fourth decimal reduction, t(4D) . CONCLUSIONS: Resistance of E. coli changed - increased - at all temperatures under study. Generally, the addition of TMAO to the growth medium protected E. coli cells, leading to an increase in their heat resistance, i.e. reduced k(max) and increased D and t(4D) values are obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: Additional knowledge on the reaction of E. coli to heat in the presence of the organic osmolyte TMAO at lethal temperatures is provided. This work contributes to an improved understanding of the level of the resistance of bacteria to heat in the presence of osmolytes.

The epidemiological profile of tuberculosis in southern Brazil in times of AIDS.

SETTING: Urban area in southern Brazil. OBJECTIVE: To investigate human immunodeficiency virus (HIV) co-infection among new cases of tuberculosis recorded in 2000 in Porto Alegre, Brazil. DESIGN: Cross-sectional population-based study. RESULTS: Among 1713 new tuberculosis cases, HIV testing was not available for 29.8% and results were unknown for 1.8%. Of 1171 with known results, 47% had HIV co-infection. HIV seropositivity was 44% higher in males. The 15-59 years age group had 3.4 times more seropositive cases than the group aged >59 years. Individuals with <8 years of schooling presented 57% more co-infection. HIV positivity was twice as frequent in extra-pulmonary and combined forms of tuberculosis as in pulmonary forms. Hospitalization was 2.4 times more common in HIV-positive individuals. The overall cure rate was 69.8%, while in co-infected patients it was 43.9%. The determinants of risk of death from tuberculosis included <8 years of schooling (PR 2.2, 95%CI 1.2-3.7), HIV seropositivity (PR 8.0, 95%CI 5.0-12.9), combined pulmonary and extra-pulmonary tuberculosis (PR 1.7, 95%CI 1.2-2.5) and diagnosis during admission rather than in out-patient clinics (PR 5.4, 95%CI 2.9-10.1). CONCLUSIONS: The co-occurrence of tuberculosis and HIV/AIDS indicates a need to integrate the control programs for these two diseases. The health care system should invest in early diagnosis and adherence to treatment for both diseases.

[Spatial risk distribution: modeling infant mortality in Porto Alegre, Rio Grande do Sul State, Brazil]. / Distribuição espacial do risco: modelagem da mortalidade infantil em Porto Alegre, Rio Grande do Sul, Brasil.

Estimation and mapping of risk profiles are the main concerns of epidemiology. This paper analyzes spatial distribution of infant mortality cases as compared to live-born controls from Porto Alegre, Rio Grande do Sul. The modeling framework adopted in this research work is a spatial point process. Under this structure, a risk measure which continuously varies over the study region is defined and estimated using generalized additive model methods. This approach has the advantage of allowing for risk factors that are simple and easy to interpret. The procedure also allows the construction of tolerance contours which help identify areas of significantly high/low risk and an overall test for the null hypothesis of constant risk over the region. Application of this method to infant mortality data showed a highly significant spatial variation in risk for neonatal mortality data and non-significant results for post-neonatal mortality data.

[Prevalence and risk factors for anemia among children in Brazil]. / Prevalência e determinantes de anemia em crianças de Porto Alegre, RS, Brasil.

OBJECTIVE: To verify the prevalence of anemia among children aged 0 to 36 months, who attend public day care centers in Porto Alegre, Brazil, and assess its possible risk factors. METHODS: A cross-sectional study was carried out in 557 children aged 0 to 36 months of all public day care centers in Porto Alegre. Anthropometric measurements and hemoglobin levels were performed. The portable HemoCue photometer was employed to measure hemoglobin levels, and anemia was considered when the hemoglobin level was below 11 g/dl. Information regarding each child was obtained by means of a questionnaire applied to the mother. The association of the variables studied to anemia was analyzed using the log-binomial regression technique applied to the hierarchical model. RESULTS: A 47.8% prevalence of anemia was found in this population. The risk factors for anemia in the studied group were: families with per capita income equal or less than one monthly minimal wage (prevalence ratio - RP =1.6), age between 12 and 23 months (RP=1.4), and having 2 or more siblings younger than 5 years old (RP=1.4). CONCLUSIONS: There is a high prevalence of anemia among children aged 0 to 36 months in public day care centers, especially among children with the lowest socioeconomic level, in the 12 to 23 months age group, and who have 2 or more siblings under 5 years of age, indicating that there is an urgent need for effective measures to fight and prevent this condition.

Direct isolation in vitro of Trypanosoma brucei from man and other animals, and its potential value for the diagnosis of gambian trypanosomiasis.

A recently described simple kit for isolating African trypanosomes in vitro (KIVI) was tested further with blood samples from man and other animals in Côte d'Ivoire and République du Congo. A high rate of success was achieved, with positive cultures being found 5-36 d after inoculation. The method was also of value in diagnosis. Parasitaemia was initially detected by the haematocrit method; in addition, the mini-anion exchange column was used for human blood and lymph fluid from patients with swollen glands was examined. The card agglutination test (CATT) was applied to the human blood samples. In Côte d'Ivoire, all 5 parasitaemic patients, who were also positive by CATT, yielded positive KIVI cultures. Of 15 animals, 2 parasitaemic and 10 apparently aparasitaemic individuals gave positive cultures. In the Congo, none of the 22 animals was parasitaemic and none gave a positive culture. Of 647 human subjects initially screened, 61, mostly with a positive CATT, were examined by KIVI; 20 gave positive cultures. Seven of these cultures originated from patients in whom no trypanosome had been seen in blood or lymph fluid, although blood from 2 parasitaemic patients failed to yield positive KIVI cultures. Some patients with CATT-negative whole blood and/or serum were positive by KIVI.

High homology between variant surface glycoprotein gene expression sites of Trypanosoma brucei and Trypanosoma gambiense.

The AnTat 11.17 variant surface glycoprotein (VSG) is synthesized in both metacyclic and bloodstream forms of Trypanosoma gambiense. We have characterized the AnTat 11.17 gene, and analyzed its expression site (ES) in the bloodstream form by Southern and Northern blotting with probes from the Trypanosoma brucei AnTat 1.3A VSG ES, and by run-on transcription. The AnTat 11.17 ES is located at the end of a 700-kb chromosome. It appears to contain all the genes (ESAGs, for Expression Site-Associated Genes) present in the AnTat 1.3A VSG ES, with the possible exception of ESAG 1. Limited nucleotide sequence analysis of ESAG cDNAs from the AnTat 11.17 ES shows considerable conservation with ESAGs of T. brucei. The transcription promoter of the AnTat 11.17 VSG ES, localized by virtue of the specific accumulation of promoter-proximal transcripts which occurs following UV irradiation, was found to be at the same relative position to the first ESAG (ESAG 7) as in AnTat 1.3A.

Telomere interactions may condition the programming of antigen expression in Trypanosoma brucei.

The AnTat 1.1 antigen type typically occurs late in a chronic infection by the EATRO 1125 stock of Trypanosoma brucei. The AnTat 1.1 gene, which is located 24 kb from a chromosome end, seems exclusively expressed by acting as a donor in gene conversion events targeted to the telomeric expression site. We report that this gene is sufficiently provided with the homology blocks required for recombination with the expression site, and is not interrupted by stop codons up to the 3' block of homology. A possible reason for its low probability of activation is an inverse orientation with respect to the proximal chromosome end, since, if correctly positioned, it is readily expressed at an early stage of infection, following gene conversion. This suggests that interactions between chromosome ends may precede and favour the rearrangements leading to antigenic variation.

Characterization of genes coding for two major metacyclic surface antigens in Trypanosoma brucei.

In African trypanosomes, only a very small fraction of the total repertoire of variable antigen types (VATs) is expressed by the metacyclic form. In Trypanosoma brucei stock EATRO 1125, the VATs AnTat 1.30 and 1.45 are reproducibly present in about 15% and 4% of the metacyclic population, respectively. The genes encoding the corresponding antigens or variant surface glycoproteins (VSGs) are in telomeres of large chromosomes, as are some non-metacyclic VSG genes from the same stock. Their activation mechanism has been studied in seven independent clones, 3 of which, referred to as 'first wave' metacyclic VATs (M-VATs), have been cloned from the first wave of parasitemia after cyclic transmission. In all these clones, activation of the antigen gene was linked to the transposition of an expression linked copy (ELC) of the gene to a telomeric expression site. For first wave M-VATs, this site seems variable, although restricted to large chromosomes, and it can be re-used for VSG gene expression in the bloodstream form. In 'late bloodstream' M-VATs, isolated from established chronic infections, the active expression site, at the end of a 200 kb chromosome, is the one preferred for the expression of late antigen types. It can be concluded that no characteristic feature in the genomic location and expression mechanism can distinguish metacyclic antigen genes from those expressed in the bloodstream forms, although the control of their expression must clearly be different.

Trypanosoma brucei: the extent of conversion in antigen genes may be related to the DNA coding specificity.

The boundaries of gene conversion in variant-specific antigen genes have been determined in six clones of Trypanosoma brucei. In each clone, antigenic switching involved interaction between two telomeric members of the AnTat 1.1 multigene family, which share extensive homology throughout their coding regions. All conversion events occurred by substitution of faithful copies of donor sequences. Conversion endpoints were nonrandomly distributed. In four clones, the 5' conversion limit was near the antigen translation initiation codon, while in three clones, the 3' conversion limit was located at the "hinge" between the two major antigen domains. In one case, two segmental conversions were involved in antigen switching. These observations reveal that antigen gene conversion can occur without generating point mutations, and suggest that postrecombinational selection may impose a limit on the number of possible rearrangements within antigen genes.

Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes.

In African trypanosomes, antigenic variation is achieved through differential gene activation, with one antigen gene being expressed at a time among a large collection of antigen-specific sequences. Transcription of the antigen gene always takes place in a telomere, but different telomeres can alternatively act as the expression site. Telomeric antigen genes can be expressed without apparent DNA rearrangement, but they can also, like non-telomeric genes, have access to the telomeric expression site through a duplicative transposition mechanism resembling gene conversion. We report here that, as previously suggested, telomeric genes may use another route to be activated. This mechanism of gene activation is by reciprocal crossing-over upstream from the gene, in the so-called 'barren' region. This allows the antigen gene to be placed in the previously activated telomere, while inactivating the formerly expressed gene by recombination into a silent environment. At least for the telomeric antigen gene described here, three possible activation mechanisms coexist.

Inactivation and reactivation of a variant-specific antigen gene in cyclically transmitted Trypanosoma brucei.

In Trypanosoma brucei, the activation of the variant-specific antigen gene AnTat 1.1 proceeds by the synthesis of an additional gene copy, the AnTat 1.1 ELC, which is transposed to a new location, the expression site, where it is transcribed. Using the AnTat 1.1 variant to infect flies, we investigated the fate of the AnTat 1.1 ELC during cyclic transmission of T. brucei. We show here that the AnTat 1.1 ELC is conserved in procyclic trypanosomes, obtained either from the midgut of infected Glossina or from cultures, and in metacyclic trypanosomes, although the AnTat 1.1 serotype is not detected among metacyclic antigen types. This same AnTat 1.1 ELC, which is thus silent as the parasite develops in the insect vector, can be reactivated without duplication during the first parasitemia wave following cyclical transmission. This re-expression of the conserved ELC accounts for the early appearance of the 'ingested' antigenic type after passage through the fly.

Translocation alters the activation rate of a trypanosome surface antigen gene.

We report here the characterization of the gene coding for AnTat 1.13, a very late variable antigen type (VAT) from Trypanosoma b. brucei. This gene is chromosome-internal and it is activated by the duplicative mechanism. Like in another case of late VAT expression (1), its expression-linked copy (ELC) is flanked by "companion" sequences. It was possible to convert the late expression of this VAT into an early one, by changing the location of the gene in the genome. This has been achieved by selecting an AnTat 1.6 clone among heterotypes arising in the AnTat 1.13 cloned population. Indeed, this particular derivation leads to the conservation of the AnTat 1.13 ELC as a new telomeric member of the gene family, and this conserved ELC (or ex-ELC) appears to be preferentially activable. The telomeric position and other factors possibly involved in early or late antigen gene expression are discussed; in this respect, we propose that some antigen genes are rarely activated because their duplicative transposition requires the presence, in the expression site, of "companion" sequences only shared by a limited number of other genes.