Increase of [(18)F]FLT Tumor Uptake In Vivo Mediated by FdUrd: Toward Improving Cell Proliferation Positron Emission Tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D: -glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Effects of differential taxation on factor accumulation and growth

In this paper we try to analyze the role of fiscal policy in fostering a higher participation of the different production factors in the human capital production sector in the long-run. Introducing a tax on physical capital and differentiating both a tax on raw labor wage and a tax on skills or human capital we also attempt to present a way to influence inequality as measured by the skill premium, thus trying to relate the increase in human capital with the decrease in income inequality. We will do that in the context of a non-scale growth model.The model here is capable to alter the shares of private factors devoted to each of the two production sectors, final output and human capital, and affect inequality in a different way according to the different tax changes. The simulation results derived in the paper show how a human capital (skills) tax cut, which could be interpreted as a reduction in progressivity, ends up increasing both the shares of labor and physical capital devoted to the production of knowledge and decreasing inequality. Moreover, a raw labor wage tax decrease, which could also be interpreted as an increase in the progressivity of the system, increases the share of labor devoted to the production of final output and increases inequality. Finally, a physical capital tax decrease reduces the share of physical capital devoted to the production of knowledge and allows for a lower inequality value. Nevertheless, none of the various types of taxes ends up changing the share of human capital in the knowledge production, which will deserve our future attention

Is there a connection between the tax administration and the political power?

This paper offers empirical evidence from Spain of a connection between the tax administration and the political power. Firstly, the regional tax administration is not immune to the budgetary situation of regional government, and tends to exert a greater (or lesser) effort in tax collection the greater (or lower) the (expected) public deficit. At the same time, the system of unconditional grants from the central layer of government provokes an ¿income effect¿ which disincentivises the efforts of the tax administration. Secondly, these efforts also decrease when the margin to lose a parliamentary seat in an electoral district is cut, although the importance of this disincentive decreases according to the parliamentary strength of the incumbent

Aggregate shocks or vertical tax interdependence? Evidende from gasoline and cigarettes

[cat] Besley i Rosen -1998- van ser els primers autors en estimar empíricament la rellevància de les externalitats impositives verticals. Aquests autors varen fer-ho per al cas dels impostos sobre la benzina i el tabac, en concret, per al cas dels EEUU. Ara bé, no varen tenir en compte les diferències en el nivell de vida entre Estats: àrees amb un nivell elevat paguen menys en termes reals que àrees amb un nivell de vida baix, doncs l'impost unitari sobre la benzina o sobre el tabac no difereix d'acord amb l'Estat on l'impost s'aplica. En conseqüència, proposem que la competència impositiva vertical sigui estimada deflactant totes les variables monetàries utilitzant l'anomenat "House Price Index (HPI)", el qual està disponible al nivell dels Estats. Això genera una variable impositiva federal expressada en termes reals i que presenta variació entre Estats. Aquesta estratègia empírica ens permet diferenciar entre la interdependència vertical entre els tipus impositius federals i els estatals de shocks agregats al llarg del temps, utilitzant dades per als EEUU durant el període 1975 a 2006 per a benzina i tabac. Trobem una nivell significatiu de competència impositiva horitzontal, la qual és més elevada en el cas del tabac, però en cap cas reacció impositiva vertical. Els resultats són robustos al període analitzat.

The effects of tax deductibility on the mix of property taxes and use charges: an empirical analysis of the spanish case

This paper tests some hypothesis about the determinants of the local tax structure. In particular, we focus on the effects that the property tax deductibility in the national income tax has on the relative use of the property tax and user charges. We deal with the incentive effects that local governments face regarding the different sources of revenue by means of a model in which the local tax structure and the level of public expenditure arise as a result of the maximizing behaviour of local politicians subject to the economic effects of the tax system. We attempt to test the hypothesis developed with data corresponding to a set of Spanish municipalities during the period 1987-9l. We find that tax deductibility provides incentives to raise revenues from the property tax but does not introduce a biass against user charges or in favor of overall spending growth

Tax differentials and agglomeration economies in intraregional firm location

This paper analyses empirically how differences in local taxes affect the intraregional location of new manufacturing plants. These effects are examined within the random profit maximization framework while accounting for the presence of different types of agglomeration economies (localization/ urbanization/ Jacobs¿ economies) at the municipal level. We look at the location decision of more than 10,000 establishments locating between 1996 and 2003 across more than 400 municipalities in Catalonia, a Spanish region. It is necessary to restrict the choice set to the local labor market and, above all, to control for agglomeration economies so as to identify the effects of taxes on the location of new establishments.

Effect of a temperature increase in the non-noxious range on proton-evoked ASIC and TRPV1 activity.

Acid-sensing ion channels (ASICs) are neuronal H(+)-gated cation channels, and the transient receptor potential vanilloid 1 channel (TRPV1) is a multimodal cation channel activated by low pH, noxious heat, capsaicin, and voltage. ASICs and TRPV1 are present in sensory neurons. It has been shown that raising the temperature increases TRPV1 and decreases ASIC H(+)-gated current amplitudes. To understand the underlying mechanisms, we have analyzed ASIC and TRPV1 function in a recombinant expression system and in dorsal root ganglion (DRG) neurons at room and physiological temperature. We show that temperature in the range studied does not affect the pH dependence of ASIC and TRPV1 activation. A temperature increase induces, however, a small alkaline shift of the pH dependence of steady-state inactivation of ASIC1a, ASIC1b, and ASIC2a. The decrease in ASIC peak current amplitudes at higher temperatures is likely in part due to the observed accelerated open channel inactivation kinetics and for some ASIC types to the changed pH dependence of steady-state inactivation. The increase in H(+)-activated TRPV1 current at the higher temperature is at least in part due to a hyperpolarizing shift in its voltage dependence. The contribution of TRPV1 relative to ASICs to H(+)-gated currents in DRG neurons increases with higher temperature and acidity. Still, ASICs remain the principal pH sensors of DRG neurons at 35°C in the pH range ≥6.

Beyond the Toledo agreement : the intergenerational impact of the spanish pension reform

The paper examines the intergenerational impact of the Spanish public pension system after the 1997 Pension Reform Act. Working within a Generational Accounting framework, we find that maintaining the new legal setting could leave future generations with liabilities as high as 176 percent of base year GDP. As the recent reform measures have been insufficient to achieve the sustainability of the current pension system, we also analyse the impact of alternative reform strategies. Within the current pay-as-you-go setting, a further improvement to tax-benefit linkage in line with the original spirit of the Toledo Agreement is shown to yield and intergenerationally more balanced outcome,than an increase in the retirement age or an expansion of public subsidies financed through indirect taxes. Finally, we examine the generational impact of a move toward a partially funded pension system which might restore theintergenerational balance

Tax differentials and agglomeration economies in intraregional firm location

This paper analyses empirically how differences in local taxes affect the intraregional location of new manufacturing plants. These effects are examined within the random profit maximization framework while accounting for the presence of different types of agglomeration economies (localization/ urbanization/ Jacobs¿ economies) at the municipal level. We look at the location decision of more than 10,000 establishments locating between 1996 and 2003 across more than 400 municipalities in Catalonia, a Spanish region. It is necessary to restrict the choice set to the local labor market and, above all, to control for agglomeration economies so as to identify the effects of taxes on the location of new establishments.

Effects of differential taxation on factor accumulation and growth

In this paper we try to analyze the role of fiscal policy in fostering a higher participation of the different production factors in the human capital production sector in the long-run. Introducing a tax on physical capital and differentiating both a tax on raw labor wage and a tax on skills or human capital we also attempt to present a way to influence inequality as measured by the skill premium, thus trying to relate the increase in human capital with the decrease in income inequality. We will do that in the context of a non-scale growth model.The model here is capable to alter the shares of private factors devoted to each of the two production sectors, final output and human capital, and affect inequality in a different way according to the different tax changes. The simulation results derived in the paper show how a human capital (skills) tax cut, which could be interpreted as a reduction in progressivity, ends up increasing both the shares of labor and physical capital devoted to the production of knowledge and decreasing inequality. Moreover, a raw labor wage tax decrease, which could also be interpreted as an increase in the progressivity of the system, increases the share of labor devoted to the production of final output and increases inequality. Finally, a physical capital tax decrease reduces the share of physical capital devoted to the production of knowledge and allows for a lower inequality value. Nevertheless, none of the various types of taxes ends up changing the share of human capital in the knowledge production, which will deserve our future attention

Aggregate shocks or vertical tax interdependence? Evidende from gasoline and cigarettes

[cat] Besley i Rosen -1998- van ser els primers autors en estimar empíricament la rellevància de les externalitats impositives verticals. Aquests autors varen fer-ho per al cas dels impostos sobre la benzina i el tabac, en concret, per al cas dels EEUU. Ara bé, no varen tenir en compte les diferències en el nivell de vida entre Estats: àrees amb un nivell elevat paguen menys en termes reals que àrees amb un nivell de vida baix, doncs l'impost unitari sobre la benzina o sobre el tabac no difereix d'acord amb l'Estat on l'impost s'aplica. En conseqüència, proposem que la competència impositiva vertical sigui estimada deflactant totes les variables monetàries utilitzant l'anomenat "House Price Index (HPI)", el qual està disponible al nivell dels Estats. Això genera una variable impositiva federal expressada en termes reals i que presenta variació entre Estats. Aquesta estratègia empírica ens permet diferenciar entre la interdependència vertical entre els tipus impositius federals i els estatals de shocks agregats al llarg del temps, utilitzant dades per als EEUU durant el període 1975 a 2006 per a benzina i tabac. Trobem una nivell significatiu de competència impositiva horitzontal, la qual és més elevada en el cas del tabac, però en cap cas reacció impositiva vertical. Els resultats són robustos al període analitzat.

Top income shares in Portugal over the twentieth century

[cat] L’objectiu d’aquest article és presentar nova evidència estadística sobre l’evolució de les desigualtats econòmiques a Portugal a llarg termini. L’explotació de les fonts fiscals portugueses ha permès l’estimació annual de les top income shares des de 1936. La construcció d’aquesta nova sèrie s’ha fet seguint la metodologia emprada per Piketty (2001). Aquesta nova sèrie revela una caiguda de les top income shares durant la Segona Guerra Mundial, seguida d’una recuperació fins a principis dels anys cinquanta. Des de mitjans dels cinquanta fins a principis dels anys vuitanta hi ha una caiguda dràstica de les top income shares. Per acabar, durant els anys noranta les top income shares tornen a augmentar. Aquesta pauta és molt similar a la viscuda en altres països: la reducció de les top income shares durant l’època daurada és compartida per tots els països estudiats i el seu increment als anys noranta sembla que alinea Portugal amb la pauta seguida pels països Anglosaxons.

Is there a connection between the tax administration and the political power?

This paper offers empirical evidence from Spain of a connection between the tax administration and the political power. Firstly, the regional tax administration is not immune to the budgetary situation of regional government, and tends to exert a greater (or lesser) effort in tax collection the greater (or lower) the (expected) public deficit. At the same time, the system of unconditional grants from the central layer of government provokes an ¿income effect¿ which disincentivises the efforts of the tax administration. Secondly, these efforts also decrease when the margin to lose a parliamentary seat in an electoral district is cut, although the importance of this disincentive decreases according to the parliamentary strength of the incumbent

The effects of tax deductibility on the mix of property taxes and use charges: an empirical analysis of the spanish case

This paper tests some hypothesis about the determinants of the local tax structure. In particular, we focus on the effects that the property tax deductibility in the national income tax has on the relative use of the property tax and user charges. We deal with the incentive effects that local governments face regarding the different sources of revenue by means of a model in which the local tax structure and the level of public expenditure arise as a result of the maximizing behaviour of local politicians subject to the economic effects of the tax system. We attempt to test the hypothesis developed with data corresponding to a set of Spanish municipalities during the period 1987-9l. We find that tax deductibility provides incentives to raise revenues from the property tax but does not introduce a biass against user charges or in favor of overall spending growth

The contribution of rectangularization to the secular increase of life expectancy: an empirical study.

BACKGROUND: In low-mortality countries, life expectancy is increasing steadily. This increase can be disentangled into two separate components: the delayed incidence of death (i.e. the rectangularization of the survival curve) and the shift of maximal age at death to the right (i.e. the extension of longevity). METHODS: We studied the secular increase of life expectancy at age 50 in nine European countries between 1922 and 2006. The respective contributions of rectangularization and longevity to increasing life expectancy are quantified with a specific tool. RESULTS: For men, an acceleration of rectangularization was observed in the 1980s in all nine countries, whereas a deceleration occurred among women in six countries in the 1960s. These diverging trends are likely to reflect the gender-specific trends in smoking. As for longevity, the extension was steady from 1922 in both genders in almost all countries. The gain of years due to longevity extension exceeded the gain due to rectangularization. This predominance over rectangularization was still observed during the most recent decades. CONCLUSIONS: Disentangling life expectancy into components offers new insights into the underlying mechanisms and possible determinants. Rectangularization mainly reflects the secular changes of the known determinants of early mortality, including smoking. Explaining the increase of maximal age at death is a more complex challenge. It might be related to slow and lifelong changes in the socio-economic environment and lifestyles as well as population composition. The still increasing longevity does not suggest that we are approaching any upper limit of human longevity.