Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response

Objective: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease. Methods and results: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods. Promoter activity was investigated by using reporter expression experiments in human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, with measurements of plasma markers linked to COX-2 activity, were genotyped for association studies. A common COX-2 promoter variant, -765G>C, was found and shown to be carried by >25% of a group of healthy UK subjects. The -765C allele had significantly lower promoter activity compared with -765G, basally (28±3% lower, P<0.005) and in serum-stimulated cells (31±2% lower, P<0.005). In patients subjected to coronary artery bypass graft surgery, the magnitude of rise in levels of C-reactive protein (CRP) was strongly genotype dependent. Compared with -765G homozygotes, patients carrying the -765C allele had significantly lower plasma CRP levels at 1 to 4 days after surgery (14% lower at the peak of CRP levels on day 3, P<0.05 for all time points). Conclusions: For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed

Электромагнитная обстановка в компьютерных классах, ее контроль и методы нормализации

Приведены результаты экспериментального исследования электромагнитной обстановки (ЭМО), создаваемой компьютерами в учебных помещениях. Показано, что в зависимости от места расположения компьютера меняются размеры, создаваемой им зоны опасного излучения, даны рекомендации по контролю ЭМО и методам ее нормализации

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

Spatial representation of temporal information through spike timing dependent plasticity

We suggest a mechanism based on spike time dependent plasticity (STDP) of synapses to store, retrieve and predict temporal sequences. The mechanism is demonstrated in a model system of simplified integrate-and-fire type neurons densely connected by STDP synapses. All synapses are modified according to the so-called normal STDP rule observed in various real biological synapses. After conditioning through repeated input of a limited number of of temporal sequences the system is able to complete the temporal sequence upon receiving the input of a fraction of them. This is an example of effective unsupervised learning in an biologically realistic system. We investigate the dependence of learning success on entrainment time, system size and presence of noise. Possible applications include learning of motor sequences, recognition and prediction of temporal sensory information in the visual as well as the auditory system and late processing in the olfactory system of insects.Comment: 13 pages, 14 figures, completely revised and augmented versio

Explorar e Investigar em Matemática: Uma Actividade Fundamental no Ensino e na Aprendizagem

Investigar, ensinar e aprender são actividades que podem estar presentes, de forma articulada, no ensino-aprendizagem da Matemática e na actividade profissional do professor. Para isso, é necessário conceber tarefas que possam ser o ponto de partida para investigações e explorações matemáticas dos alunos e discutir o modo como podem ser trabalhadas na sala de aula. Recorrendo a exemplos de actividades realizadas por professores de Matemática portugueses, analiso a actividade de aprendizagem suscitada por tarefas deste tipo e discuto as respectivas potencialidades. Finalmente, refiro as condições respeitantes à cultura profissional dos professores que podem favorecer uma actividade de investigação sobre a sua própria profissional, com relevo para a colaboração e a dimensão associativa.Researching, teaching and learning are activities that may be present, in coordination, teaching and learning of mathematics in the work of the teacher. Therefore, it is necessary to design tasks that may be the starting point for mathematical investigations and explorations of the students and discuss how they can be worked in the classroom. Drawing on examples of activities carried out by Portuguese teachers of mathematics by examining the activity of learning raised by such tasks and discuss their potencial. Finally, I refer to conditions relating to the professional culture of teachers who can promote the research activity on their own training, with an emphasis on collaboration and associative dimension

Wikipedia as informal self-education for clinical decision-making in medical practice

Background For almost any topic, a Wikipedia page will appear among the first ten items of a search online. Wikipedia is also a site whose quality and reliability has been called into question. Methods In this paper, we aim to discuss medical practitioners’ use of Wikipedia, what this consists of and what it might be. We consider the context and history of Wikipedia before discussing the relationship between Wikipedia and the medical profession. In so doing, we will consider Wikipedia as a means of informal self-education and the extent to which it might inform clinical decision-making. We compare with the existing literature results from our two small-scale empirical studies of Wikipedia and clinical decision-making. Results Notwithstanding issues over quality and reliability, Wikipedia’s rules on verifiability are such that its articles are very heavily referenced, and this is just as true of health-related articles. The Cochrane/Wikipedia Initiative in improving the quality and reliability of medical and health pages in Wikipedia is significant in increasing reliability. Our respondents largely concurred with the results from earlier studies on the use of Wikipedia by medical practitioners. Conclusion Perhaps the very doubt over Wikipedia’s accuracy is its greatest strength as a means of informal education of doctors. That medical and health articles on Wikipedia can be so fully referenced and still be doubted is arguably a good thing and one whose effects may be spread into other, more trusted, publications. Hence, one might envisage a future where no one source is taken automatically on trust. Keywords Wikipedia, informal education, continued professional development, medical education

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

A robust spectral method for solving Heston’s model

In this paper, we consider the Heston’s volatility model (Heston in Rev. Financ. Stud. 6: 327–343, 1993]. We simulate this model using a combination of the spectral collocation method and the Laplace transforms method. To approximate the two dimensional PDE, we construct a grid which is the tensor product of the two grids, each of which is based on the Chebyshev points in the two spacial directions. The resulting semi-discrete problem is then solved by applying the Laplace transform method based on Talbot’s idea of deformation of the contour integral (Talbot in IMA J. Appl. Math. 23(1): 97–120, 1979)

Congestion in a macroscopic model of self-driven particles modeling gregariousness

International audienceWe analyze a macroscopic model with a maximal density constraint which describes short range repulsion in biological systems. This system aims at modeling finite-size particles which cannot overlap and repel each other when they are too close. The parts of the fluid where the maximal density is reached behave like incompressible fluids while lower density regions are compressible. This paper investigates the transition between the compressible and incompressible regions. To capture this transition, we study a one-dimensional Riemann problem and introduce a perturbation problem which regularizes the compressible-incompressible transition. Specific difficulties related to the non-conservativity of the problem are discussed