Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC.Conclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

Periodic orbits near a heteroclinic loop formed by one dimensional orbit and a 2-dimensional manifold: application to the charged collinear 3-body problem

The paper is devoted to the study of a type of differential systems which appear usually in the study of some Hamiltonian systems with 2 degrees of freedom. We prove the existence of infinitely many periodic orbits on each negative energy level. All these periodic orbits pass near the total collision. Finally we apply these results to study the existence of periodic orbits in the charged collinear 3–body problem.

Optimal feedback control rules sensitive to controlled endogenous risk-aversion

The objective of this paper is to correct and improve the results obtained by Van der Ploeg (1984a, 1984b) and utilized in the theoretical literature related to feedback stochastic optimal control sensitive to constant exogenous risk-aversion (see, Jacobson, 1973, Karp, 1987 and Whittle, 1981, 1989, 1990, among others) or to the classic context of risk-neutral decision-makers (see, Chow, 1973, 1976a, 1976b, 1977, 1978, 1981, 1993). More realistic and attractive, this new approach is placed in the context of a time-varying endogenous risk-aversion which is under the control of the decision-maker. It has strong qualitative implications on the agent's optimal policy during the entire planning horizon.

The loop group and the cobar construction

"Vegeu el resum a l'inici del document del fitxer adjunt."

Estudio y diseño de filtros pasobanda y en banda dual basados en resonadores microstrip open-loop acoplados

El proyecto está dedicado al estudio y diseño de filtros paso-banda y en banda dual con tecnología microstrip mediante estructuras resonantes de tipo open-loop. Se ha llevado a cabo el diseño de un filtro paso-banda con respuesta Chebyshev, un filtro pasobanda con ceros de transmisión y un filtro de banda dual para WCDMA y WiFi, empleado el método de diseño para filtros basados en resonadores inter-acoplados. Se presentan los modelos eléctricos de los filtros de RF simulados junto con sus respectivos layouts y se comparan las respuestas obtenidas de los dispositivos con las respuestas ideales. En el proyecto se realiza un estudio del comportamiento de los diferentes tipos de acoplamiento entre resonadores open-loop en función de la geometría de la estructura. Las tendencias de comportamiento de los acoplamientos permiten el diseño y colocación de los resonadores para satisfacer las especificaciones del filtro.

Lack of CB1 receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behavior and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared to wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the dorsal raphe nucleus, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an overexpression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the dorsal raphe nucleus by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.

Per-antenna rate and power control for MIMO layered architectures in the low- and high-power regimes

In a MIMO layered architecture, several codewordsare transmitted from a multiplicity of antennas. Although thespectral efficiency is maximized if the rates of these codewordsare separately controlled, the feedback rate within the linkadaptation loop is reduced if they are constrained to be identical.This poses a direct tradeoff between performance andfeedback overhead. This paper provides analytical expressionsthat quantify the difference in spectral efficiency between bothapproaches for arbitrary numbers of antennas. Specifically, thecharacterization takes place in the realm of the low- and highpowerregimes via expansions that are shown to have a widerange of validity.In addition, the possibility of adjusting the transmit powerof each codeword individually is considered as an alternative tothe separate control of their rates. Power allocation, however,turns out to be inferior to rate control within the context of thisproblem.

The importance of relative performance feedback information: Evidence from a natural experiment using high school students

We study the effect of providing relative performance feedback information onperformance, when individuals are rewarded according to their absolute performance. Anatural experiment that took place in a high school offers an unusual opportunity to testthis effect in a real-effort setting. For one year only, students received information thatallowed them to know whether they were performing above (below) the class average aswell as the distance from this average. We exploit a rich panel data set and find that theprovision of this information led to an increase of 5% in students grades. Moreover, theeffect was significant for the whole distribution. However, once the information wasremoved, the effect disappeared. To rule out the concern that the effect may beartificially driven by teachers within the school, we verify our results using nationallevel exams (externally graded) for the same students, and the effect remains.

The benefits of limited feedback in organizations

In most firms, managers periodically assess workers' performance. Evidence suggeststhat managers withhold information during these reviews, and some observersargue that this necessarily reduces surplus. This paper assesses the validity of thisargument when workers have career concerns. Disclosure has two effects: it exposesthe worker to uncertainty about future effort levels, but allows him to use current effortto influence his employer's beliefs about future effort. The surplus-maximizingdisclosure policy reveals output realizations in the center of the distribution, butnot in the tails. Thus, it is efficient for firms to reveal some but not all performanceinformation.

Is confidence in decisions related to feedback? Evidence-and lack of evidence-from random samples of real-world managerial behavior?

Confidence in decision making is an important dimension of managerialbehavior. However, what is the relation between confidence, on the onehand, and the fact of receiving or expecting to receive feedback ondecisions taken, on the other hand? To explore this and related issuesin the context of everyday decision making, use was made of the ESM(Experience Sampling Method) to sample decisions taken by undergraduatesand business executives. For several days, participants received 4 or 5SMS messages daily (on their mobile telephones) at random moments at whichpoint they completed brief questionnaires about their current decisionmaking activities. Issues considered here include differences between thetypes of decisions faced by the two groups, their structure, feedback(received and expected), and confidence in decisions taken as well as inthe validity of feedback. No relation was found between confidence indecisions and whether participants received or expected to receivefeedback on those decisions. In addition, although participants areclearly aware that feedback can provide both confirming and disconfirming evidence, their ability to specify appropriatefeedback is imperfect. Finally, difficulties experienced inusing the ESM are discussed as are possibilities for further researchusing this methodology.

The provision of relative performance feedback information: An experimental analysis of performance and happiness

This paper studies the effect of providing relative performance feedback information onindividual performance and on individual affective response, when agents are rewardedaccording to their absolute performance. In a laboratory set-up, agents perform a realeffort task and when receiving feedback, they are asked to rate their happiness, arousaland feeling of dominance. Control subjects learn only their absolute performance, whilethe treated subjects additionally learn the average performance in the session.Performance is 17 percent higher when relative performance feedback is provided.Furthermore, although feedback increases the performance independent of the content(i.e., performing above or below the average), the content is determinant for theaffective response. When subjects are treated, the inequality in the happiness and thefeeling of dominance between those subjects performing above and below the averageincreases by 8 and 6 percentage points, respectively.

Modelling state dependence and feedback effects between poverty, employment and parental home emancipation among European youth

Youth is one of the phases in the life-cycle when some of the most decisivelife transitions take place. Entering the labour market or leaving parentalhome are events with important consequences for the economic well-beingof young adults. In this paper, the interrelationship between employment,residential emancipation and poverty dynamics is studied for eight Europeancountries by means of an econometric model with feedback effects. Resultsshow that youth poverty genuine state dependence is positive and highly significant.Evidence proves there is a strong causal effect between poverty andleaving home in Scandinavian countries, however, time in economic hardshipdoes not last long. In Southern Europe, instead, youth tend to leave theirparental home much later in order to avoid falling into a poverty state that ismore persistent. Past poverty has negative consequences on the likelihood ofemployment.

Matching at one loop for the four-quark operators in NRQCD

The matching coefficients for the four-quark operators in NRQCD (NRQED) are calculated at one loop using dimensional regularization for ultraviolet and infrared divergences. The matching for the electromagnetic current follows easily from our results. Both the unequal and equal mass cases are considered. The role played by the Coulomb infrared singularities is explained in detail.

Turn-on-time statistics of modulated lasers subjected to resonant weak optical feedback

We present analytical calculations of the turn-on-time probability distribution of intensity-modulated lasers under resonant weak optical feedback. Under resonant conditions, the external cavity round-trip time is taken to be equal to the modulation period. The probability distribution of the solitary laser results are modified to give reduced values of the mean turn-on-time and its variance. Numerical simulations have been carried out showing good agreement with the analytical results.

Loop bifurcation and magnetization rotation in exchange-biased Ni/FeF2

Exchange-biased Ni/FeF2 films have been investigated using vector coil vibrating-sample magnetometry as a function of the cooling field strength HFC . In films with epitaxial FeF2 , a loop bifurcation develops with increasing HFC as it divides into two sub-loops shifted oppositely from zero field by the same amount. The positively biased sub-loop grows in size with HFC until only a single positively shifted loop is found. Throughout this process, the negative and positive (sub)loop shifts maintain the same discrete value. This is in sharp contrast to films with twinned FeF2 where the exchange field gradually changes with increasing HFC . The transverse magnetization shows clear correlations with the longitudinal subloops. Interestingly, over 85% of the Ni reverses its magnetization by rotation, either in one step or through two successive rotations. These results are due to the single-crystal nature of the antiferromagnetic FeF2 , which breaks down into two opposite regions of large domains.