c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.

The activity of adult stem cells is essential to replenish mature cells constantly lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. Here, we provide genetic evidence for an unexpected function of the c-Myc protein in the homeostasis of hematopoietic stem cells (HSCs). Conditional elimination of c-Myc activity in the bone marrow (BM) results in severe cytopenia and accumulation of HSCs in situ. Mutant HSCs self-renew and accumulate due to their failure to initiate normal stem cell differentiation. Impaired differentiation of c-Myc-deficient HSCs is linked to their localization in the differentiation preventative BM niche environment, and correlates with up-regulation of N-cadherin and a number of adhesion receptors, suggesting that release of HSCs from the stem cell niche requires c-Myc activity. Accordingly, enforced c-Myc expression in HSCs represses N-cadherin and integrins leading to loss of self-renewal activity at the expense of differentiation. Endogenous c-Myc is differentially expressed and induced upon differentiation of long-term HSCs. Collectively, our data indicate that c-Myc controls the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSCs and their niche.

Entre psychanalyse et systémique : est-ce que mon coeur balance ?

Se référant à son propre parcours psychothérapeutique qui l'a conduit de la psychanalyse à la systémique, sans qu'il n'ait dû renier les apports de sa première formation, l'auteur réfléchit sur les connivences possibles entre ces deux approches, et plus largement sur les possibilités d'une pratique psychothérapeutique non uniréférencée. Selon lui, la diversité des méthodes psychothérapeutiques ne doit pas nécessairement conduire à un éclectisme hypertolérant, souvent confusionnant. Il importe pour le psychothérapeute de se savoir ici plutôt que là, tout en maintenant une ouverture aux autres pratiques grâce à l'intégration assimilative de certaines de leurs techniques.

The epithelial sodium channel and the control of sodium balance.

Studies aiming at the elucidation of the genetic basis of rare monogenic forms of hypertension have identified mutations in genes coding for the epithelial sodium channel ENaC, for the mineralocorticoid receptor, or for enzymes crucial for the synthesis of aldosterone. These genetic studies clearly demonstrate the importance of the regulation of Na(+) absorption in the aldosterone-sensitive distal nephron (ASDN), for the maintenance of the extracellular fluid volume and blood pressure. Recent studies aiming at a better understanding of the cellular and molecular basis of ENaC-mediated Na(+) absorption in the distal part of nephron, have essentially focused on the regulation ENaC activity and on the aldosterone-signaling cascade. ENaC is a constitutively open channel, and factors controlling the number of active channels at the cell surface are likely to have profound effects on Na(+) absorption in the ASDN, and in the amount of Na(+) that is excreted in the final urine. A number of membrane-bound proteases, kinases, have recently been identified that increase ENaC activity at the cell surface in heterologous expressions systems. Ubiquitylation is a general process that regulates the stability of a variety of target proteins that include ENaC. Recently, deubiquitylating enzymes have been shown to increase ENaC activity in heterologous expressions systems. These regulatory mechanisms are likely to be nephron specific, since in vivo studies indicate that the adaptation of the renal excretion of Na(+) in response to Na(+) diet occurs predominantly in the early part (the connecting tubule) of the ASDN. An important work is presently done to determine in vivo the physiological relevance of these cellular and molecular mechanisms in regulation of ENaC activity. The contribution of the protease-dependent ENaC regulation in mediating Na(+) absorption in the ASDN is still not clearly understood. The signaling pathway that involves ubiquitylation of ENaC does not seem to be absolutely required for the aldosterone-mediated control of ENaC. These in vivo physiological studies presently constitute a major challenge for our understanding of the regulation of ENaC to maintain the Na(+) balance.

Sodium and potassium balance depends on αENaC expression in connecting tubule.

Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2-expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.

The Effect of Tax Revenue Budgeting Errors on Fiscal Balance : Evidence from Swiss cantons

This study is an empirical analysis of the impact of direct tax revenue budgeting errors on fiscal deficits. Using panel data from 26 Swiss cantons between 1980 and 2002, we estimate a single equation model on the fiscal balance, as well as a simultaneous equation model on revenue and expenditure. We use new data on budgeted and actual tax revenue to show that underestimating tax revenue significantly reduces fiscal deficits. Furthermore, we show that this effect is channeled through decreased expenditure. The effects of over and underestimation turn out to be symmetric.

Kumar's algorithm for solving Toeplitz systems of equations over finite fields

Adaptació de l'algorisme de Kumar per resoldre sistemes d'equacions amb matrius de Toeplitz sobre els reals a cossos finits en un temps 0 (n log n).

Implementation of the Rijndael-AES algorithm on a Sage-Math worksheet

La principal motivació d'aquest treball ha estat implementar l'algoritme Rijndael-AES en un full Sage-math, paquet de software matemàtic de lliure distribució i en actual desenvolupament, aprofitant les seves eines i funcionalitats integrades.

On the differential evolution algorithm and its appliation to training radial basis function networks

The parameter setting of a differential evolution algorithm must meet several requirements: efficiency, effectiveness, and reliability. Problems vary. The solution of a particular problem can be represented in different ways. An algorithm most efficient in dealing with a particular representation may be less efficient in dealing with other representations. The development of differential evolution-based methods contributes substantially to research on evolutionary computing and global optimization in general. The objective of this study is to investigatethe differential evolution algorithm, the intelligent adjustment of its controlparameters, and its application. In the thesis, the differential evolution algorithm is first examined using different parameter settings and test functions. Fuzzy control is then employed to make control parameters adaptive based on an optimization process and expert knowledge. The developed algorithms are applied to training radial basis function networks for function approximation with possible variables including centers, widths, and weights of basis functions and both having control parameters kept fixed and adjusted by fuzzy controller. After the influence of control variables on the performance of the differential evolution algorithm was explored, an adaptive version of the differential evolution algorithm was developed and the differential evolution-based radial basis function network training approaches were proposed. Experimental results showed that the performance of the differential evolution algorithm is sensitive to parameter setting, and the best setting was found to be problem dependent. The fuzzy adaptive differential evolution algorithm releases the user load of parameter setting and performs better than those using all fixedparameters. Differential evolution-based approaches are effective for training Gaussian radial basis function networks.

Analysis of torque and speed ripple producing non-idealities of frequency converters in electric drives

Electric motors driven by adjustable-frequency converters may produce periodic excitation forces that can cause torque and speed ripple. Interaction with the driven mechanical system may cause undesirable vibrations that affect the system performance and lifetime. Direct drives in sensitive applications, such as elevators or paper machines, emphasize the importance of smooth torque production. This thesis analyses the non-idealities of frequencyconverters that produce speed and torque ripple in electric drives. The origin of low order harmonics in speed and torque is examined. It is shown how different current measurement error types affect the torque. As the application environment, direct torque control (DTC) method is applied to permanent magnet synchronous machines (PMSM). A simulation model to analyse the effect of the frequency converter non-idealities on the performance of the electric drives is created. Themodel enables to identify potential problems causing torque vibrations and possibly damaging oscillations in electrically driven machine systems. The model is capable of coupling with separate simulation software of complex mechanical loads. Furthermore, the simulation model of the frequency converter's control algorithm can be applied to control a real frequency converter. A commercial frequencyconverter with standard software, a permanent magnet axial flux synchronous motor and a DC motor as the load are used to detect the effect of current measurement errors on load torque. A method to reduce the speed and torque ripple by compensating the current measurement errors is introduced. The method is based on analysing the amplitude of a selected harmonic component of speed as a function oftime and selecting a suitable compensation alternative for the current error. The speed can be either measured or estimated, so the compensation method is applicable also for speed sensorless drives. The proposed compensation method is tested with a laboratory drive, which consists of commercial frequency converter hardware with self-made software and a prototype PMSM. The speed and torque rippleof the test drive are reduced by applying the compensation method. In addition to the direct torque controlled PMSM drives, the compensation method can also beapplied to other motor types and control methods.

Dynamics of Appropriability - Finding a Balance between Efficiency and Strength in the Appropriability Regime

Building and sustaining competitive advantage through the creation of market imperfections is challenging in a constantly changing business environment - particularly since the sources of such advantages are increasingly knowledge-based. Facilitated by improved networks and communication, knowledge spills over to competitors more easily than before,thus creating an appropriability problem: the inability of an innovating firm to utilize its innovations commercially. Consequently, as the importance of intellectual assets increases, their protection also calls for new approaches. Companies have various means of protection at their disposal, and by taking advantage of them they can make intangibles more non-transferable and prevent, or at leastdelay, imitation of their most crucial intellectual assets. However, creating barriers against imitation has another side to it, and the transfer of knowledge in situations requiring knowledge sharing may be unintentionally obstructed. Theaim of this thesis is to increase understanding of how firms can balance knowledge protection and sharing so as to benefit most from their knowledge assets. Thus, knowledge protection is approached through an examination of the appropriability regime of a firm, i.e., the combination of available and effective means ofprotecting innovations, their profitability, and the increased rents due to R&D. A further aim is to provide a broader understanding of the formation and structure of the appropriability regime. The study consists of two parts. The first part introduces the research topic and the overall results of the study, and the second part consists of six complementary research publications covering various appropriability issues. The thesis contributes to the existing literature in several ways. Although there is a wide range of prior research on appropriability issues, a lot of it is restricted either to the study of individual appropriability mechanisms, or to comparing certain features of them. These approaches are combined, and the relevant theoretical concepts are clarified and developed. In addition, the thesis provides empirical evidence of the formation of the appropriability regime, which is consequently presented as an adaptive process. Thus, a framework is provided that better corresponds to the complex reality of the current business environment.

Un balance del tren de alta velocidad en Francia. Enseñanzas para el caso esapañol

La reivindicación del tren de alta velocidad por parte de un número amplio y creciente de ciudades en España, aconseja una reflexión sobre qué se puede realmente esperar de este servicio para estimular el tejido económico local. Nuestra referencia será el TGV de París a Lyon, el más antiguo en Europa, con sus posteriores ampliaciones al sur. De su estudio se puede deducir que su repercusión ha resultado muy modesta como agente dinamizador de la actividad económica local y regional. En el AVE se apunta efectivamente la misma situación, a tener por tanto muy en cuenta en el diseño del nuevo trazado y en las medidas de acompañamiento para rentabilizarlo.