Disorders of apoptosis: Mechanisms for autoimmunity in primary immunodeficiency diseases

A number of primary immunodeficiency diseases represent a paradox of immunodeficiency and autoimmunity. In this minireview, we present basic concepts of apoptosis and disorder of apoptosis as one of the mechanisms to explain such a paradox between immunodeficiency and autoimmunity, which is exemplified by autoimmune lympho-proliferative syndrome (ALPS).

Dysregulation of renal transient receptor potential melastatin 6/7 but not paracellin-1 in aldosterone-induced hypertension and kidney damage in a model of hereditary hypomagnesemia

Rationale Hyperaldosteronism, important in hypertension, is associated with electrolyte alterations, including hypomagnesemia, through unknown mechanisms. Objective To test whether aldosterone influences renal Mg(2+) transporters, (transient receptor potential melastatin (TRPM) 6, TRPM7, paracellin-1) leading to hypomagnesemia, hypertension and target organ damage and whether in a background of magnesium deficiency, this is exaggerated. Methods and results Aldosterone effects in mice selectively bred for high-normal (MgH) or low (MgL) intracellular Mg(2+) were studied. Male MgH and MgL mice received aldosterone (350 mu g/kg per day, 3 weeks). SBP was elevated in MgL. Aldosterone increased blood pressure and albuminuria and increased urinary Mg(2+) concentration in MgH and MgL, with greater effects in MgL. Activity of renal TRPM6 and TRPM7 was lower in vehicle-treated MgL than MgH. Aldosterone increased activity of TRPM6 in MgH and inhibited activity in MgL. TRPM7 and paracellin-1 were unaffected by aldosterone. Aldosterone-induced albuminuria in MgL was associated with increased renal fibrosis, increased oxidative stress, activation of mitogen-activated protein kinases and nuclear factor-NF-kappa B and podocyte injury. Mg(2+) supplementation (0.75% Mg(2+)) in aldosterone-treated MgL normalized plasma Mg(2+), increased TRPM6 activity and ameliorated hypertension and renal injury. Hence, in a model of inherited hypomagnesemia, TRPM6 and TRPM7, but not paracellin-1, are downregulated. Aldosterone further decreased TRPM6 activity in hypomagnesemic mice, a phenomenon associated with hypertension and kidney damage. Such effects were prevented by Mg(2+) supplementation. Conclusion Amplified target organ damage in aldosterone-induced hypertension in hypomagnesemic conditions is associated with dysfunctional Mg(2+)-sensitive renal TRPM6 channels. Novel mechanisms for renal effects of aldosterone and insights into putative beneficial actions of Mg(2+), particularly in hyperaldosteronism, are identified. J Hypertens 29: 1400-1410 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Natural selection and quantitative genetics of life-history traits in Western women: A twin study

Whether contemporary human populations are still evolving as a result of natural selection has been hotly debated. For natural selection to cause evolutionary change in a trait, variation in the trait must be correlated with fitness and be genetically heritable and there must be no genetic constraints to evolution. These conditions have rarely been tested in human populations. In this study, data from a large twin cohort were used to assess whether selection Will cause a change among women in contemporary Western population for three life-history traits: age at menarche, age at first reproduction, and age at menopause. We control for temporal variation in fecundity (the baby boom phenomenon) and differences between women in educational background and religious affiliation. University-educated women have 35% lower fitness than those with less than seven years education, and Roman Catholic women have about 20% higher fitness than those of other religions. Although these differences were significant, education and religion only accounted for 2% and 1% of variance in fitness, respectively. Using structural equation modeling, we reveal significant genetic influences for all three life-history traits, with heritability estimates of 0.50, 0.23, and 0.45, respectively. However, strong genetic covariation with reproductive fitness could only be demonstrated for age at first reproduction, with much weaker covariation for age at menopause and no significant covariation for age at menarche. Selection may, therefore, lead to the evolution of earlier age at first reproduction in this population. We also estimate substantial heritable variation in fitness itself, with approximately 39% of the variance attributable to additive genetic effects, the remainder consisting of unique environmental effects and small effects from education and religion. We discuss mechanisms that could be maintaining such a high heritability for fitness. Most likely is that selection is now acting on different traits from which it did in pre-industrial human populations.

Why farmers continue to use pesticides despite environmental, health and sustainability costs

Use of chemical inputs such as pesticides has increased agricultural production and productivity. However, negative externalities from such use have increased too. These externalities include damage to agricultural land, fisheries, fauna and flora. Another major externality is the unintentional destruction of beneficial predators of pests thereby increasing the virulence of many species of agricultural pests. Furthermore, increased mortality and morbidity of humans due to exposure to pesticides are recorded especially in developing countries. The costs from these externalities are large and affect farmers' returns. However, despite these high costs, farmers continue to use pesticides and in most countries in increasing quantities. In this paper, we examine this paradox and show why farmers continue to use pesticides despite the increasing costs. We also emphasize 'lock-in' aspects of pesticide use. (C) 2001 Elsevier Science B.V. All rights reserved.

Monocular and binocular distance cues: insights from visual form agnosia I (of III)

The human nervous system constructs a Euclidean representation of near (personal) space by combining multiple sources of information (cues). We investigated the cues used for the representation of personal space in a patient with visual form agnosia (DF). Our results indicated that DF relies predominantly on binocular vergence information when determining the distance of a target despite the presence of other (retinal) cues. Notably, DF was able to construct an Euclidean representation of personal space from vergence alone. This finding supports previous assertions that vergence provides the nervous system with veridical information for the construction of personal space. The results from the current study, together with those of others, suggest that: (i) the ventral stream is responsible for extracting depth and distance information from monocular retinal cues (i.e. from shading, texture, perspective) and (ii) the dorsal stream has access to binocular information (from horizontal image disparities and vergence). These results also indicate that DF was not able to use size information to gauge target distance, suggesting that intact temporal cortex is necessary for learned size to influence distance processing. Our findings further suggest that in neurologically intact humans, object information extracted in the ventral pathway is combined with the products of dorsal stream processing for guiding prehension. Finally, we studied the size-distance paradox in visual form agnosia in order to explore the cognitive use of size information. The results of this experiment were consistent with a previous suggestion that the paradox is a cognitive phenomenon.

Entanglement creation using quantum interrogation

We present some applications of high-efficiency quantum interrogation (interaction-free measurement) for the creation of entangled states of separate atoms and of separate photons. The quantum interrogation of a quantum object in a superposition of object-in and object-out leaves the object and probe in an entangled state. The probe can then be further entangled with other objects in subsequent quantum interrogations. By then projecting out those cases in which the probe is left in a particular final state, the quantum objects can themselves be left in various entangled states. In this way, we show how to generate two-, three-, and higher-qubit entanglement between atoms and between photons. The effect of finite efficiency for the quantum interrogation is delineated for the various schemes.

Quantum correlated twin atomic beams via photodissociation of a molecular Bose-Einstein condensate

We study the process of photodissociation of a molecular Bose-Einstein condensate as a potential source of strongly correlated twin atomic beams. We show that the two beams can possess nearly perfect quantum squeezing in their relative numbers.

Violation of multiparticle Bell inequalities for low- and high-flux parametric amplification using both vacuum and entangled input states

We show how polarization measurements on the output fields generated by parametric down conversion will reveal a violation of multiparticle Bell inequalities, in the regime of both low- and high-output intensity. In this case, each spatially separated system, upon which a measurement is performed, is comprised of more than one particle. In view of the formal analogy with spin systems, the proposal provides an opportunity to test the predictions of quantum mechanics for spatially separated higher spin states. Here the quantum behavior possible even where measurements are performed on systems of large quantum (particle) number may be demonstrated. Our proposal applies to both vacuum-state signal and idler inputs, and also to the quantum-injected parametric amplifier as studied by De Martini The effect of detector inefficiencies is included, and weaker Bell-Clauser-Horne inequalities are derived to enable realistic tests of local hidden variables with auxiliary assumptions for the multiparticle situation.

Estimating and evaluating the statistics of gapped local-alignment scores

We present a novel maximum-likelihood-based algorithm for estimating the distribution of alignment scores from the scores of unrelated sequences in a database search. Using a new method for measuring the accuracy of p-values, we show that our maximum-likelihood-based algorithm is more accurate than existing regression-based and lookup table methods. We explore a more sophisticated way of modeling and estimating the score distributions (using a two-component mixture model and expectation maximization), but conclude that this does not improve significantly over simply ignoring scores with small E-values during estimation. Finally, we measure the classification accuracy of p-values estimated in different ways and observe that inaccurate p-values can, somewhat paradoxically, lead to higher classification accuracy. We explain this paradox and argue that statistical accuracy, not classification accuracy, should be the primary criterion in comparisons of similarity search methods that return p-values that adjust for target sequence length.

Quantum Parrondo's games

Parrondo's paradox arises when two losing games are combined to produce a winning one. A history-dependent quantum Parrondo game is studied where the rotation operators that represent the toss of a classical biased coin are replaced by general SU(2) operators to transform the game into the quantum domain. In the initial state, a superposition of qubits can be used to couple the games and produce interference leading to quite different payoffs to those in the classical case. (C) 2002 Elsevier Science B.V. All rights reserved.

Experimental investigation of criteria for continuous variable entanglement

We generate a pair of entangled beams from the interference of two amplitude squeezed beams. The entanglement is quantified in terms of EPR paradox and inseparability criteria, with both results clearly beating the standard quantum limit. We experimentally analyze the effect of decoherence on each criterion and demonstrate qualitative differences. We also characterize the number of required and excess photons present in the entangled beams and provide contour plots of the efficacy of quantum information protocols in terms of these variables.

Optical experiments beyond the quantum limit: Squeezing entanglement and teleportation

Results of experiments recently performed are reported, in which two optical parametric amplifiers were set up to generate two independently quadrature squeezed continuous wave laser beams. The transformation of quadrature squeezed states into polarization squeezed states and into states with spatial quantum correlations is demonstrated. By utilizing two squeezed laser beams, a polarization squeezed state exhibiting three simultaneously squeezed Stokes operator variances was generated. Continuous variable polarization entanglement was generated and the Einstein-Podolsky-Rosen paradox was observed. A pair of Stokes operators satisfied both the inseparability criterion and the conditional variance criterion. Values of 0.49 and 0.77, respectively, were observed, with entanglement requiring values below unity. The inseparability measure of the observed quadrature entanglement was 0.44. This value is sufficient for a demonstration of quantum teleportation, which is the next experimental goal of the authors.

Continuous variable polarization entanglement, experiment and analysis

We generate and characterize continuous variable polarization entanglement between two optical beams. We first produce quadrature entanglement, and by performing local operations we transform it into a polarization basis. We extend two entanglement criteria, the inseparability criteria proposed by Duan et al (2000 Phys. Rev. Lett. 84 2722) and the Einstein–Podolsky–Rosen (EPR) paradox criteria proposed by Reid and Drummond (1988 Phys. Rev. Lett. 60 2731), to Stokes operators; and use them to characterize the entanglement. Our results for the EPR paradox criteria are visualized in terms of uncertainty balls on the Poincaré sphere. We demonstrate theoretically that using two quadrature entangled pairs it is possible to entangle three orthogonal Stokes operators between a pair of beams, although with a bound √3 times more stringent than for the quadrature entanglement.

Entre prescrições e singularizações : o trabalho em vias da criação

O presente texto enfoca a necessidade de tornar visíveis as múltiplas atividades industriosas atualizadas por parte dos trabalhadores em ambiente laboral regulado e ordenado, considerando as dramáticas dos usos de si como formuladoras de possíveis criações. Problematiza a incessante tensão entre instituído e instituinte como paradoxo constituinte das relações de trabalho. Aborda o que se passa nos processos de trabalho apoiando-se em alguns conceitos da abordagem ergológica e da obra de M. Foucault. Formula uma visão sobre os mundos do trabalho hoje que nos permite pensá-lo como luta cotidiana por modos de viver que afirmem a vida como tendência criadora.

Entre mortificações e resistências : a saúde e o psicotrópico no sistema prisional

A saúde e o uso do psicotrópico no sistema prisional habitam um paradoxo. O sistema penitenciário, nas últimas décadas, passou por algumas transformações. No mundo, as estatísticas apontam crescimento populacional carcerário e prisões superlotadas, em condições precárias. No Brasil, a situação não é diferente: em 10 anos a população prisional brasileira duplicou e as condições de confinamento são paupérrimas, o que acaba contribuindo para a prevalência de doenças infectocontagiosas. Diante desta realidade, em 2003 homologou-se o Plano Nacional de Saúde no Sistema Penitenciário (PNSSP) que, em consonância com os princípios do Sistema Único de Saúde, visa garantir a integralidade e a universalidade de acesso aos serviços de saúde para a população penitenciária. O estado do Espírito Santo aderiu ao PNSSP e formulou o Plano Operativo Estadual de Atenção Integral à Saúde da População Prisional (2004), contudo, foi a partir de 2010 que se efetivou o acesso aos serviços de saúde prisional capixaba. Neste contexto, a pesquisa de mestrado buscou investigar as práticas de saúde no sistema prisional e as formas de usos do psicotrópico por presos da Penitenciária de Segurança Máxima II (PSMA II), localizada no Complexo Penitenciário de Viana, Espírito Santo. Para tanto, foi necessário habitar o sistema penitenciário capixaba e realizar entrevistas semiestruturadas com profissionais da gestão de saúde prisional da Secretaria Estadual de Justiça do Espírito Santo, com profissional da área da medicina psiquiátrica e com presos da PSMA II. Dessa forma, foi possível observar que a saúde no sistema penitenciário, bem como os usos do psicotrópico, encontram-se em um espaço poroso. As práticas de saúde podem fortalecer estratégias de controle e produzir mortificação, como podem escapar dos investimentos biopolíticos e produzir resistência. O uso do medicamento psicotrópico por sujeitos privados de liberdade encontra-se nessa mesma ambivalência: podem servir como instrumentos regularizadores de captura, como podem produzir autonomia nas suas formas de uso pelos presos. Por fim, entre mortificações e resistências, afirma-se que é o próprio preso que administrará os tensionamentos desse paradoxo e irá produzir vida, potência de vida.