Bosonization in d > 2 dimensions

I discuss in this talk a bosonization approach recently developed. It leads to the (exact) bosonization rule for fermion currents in d > 2 dimensions and also provides a systematic way of constructing the bosonic action in different regimes.Comment: Talk given at "Trends in Theoretical Physics, CERN - Santiago de Compostela - La Plata Meeting", La Plata, April 1997, 34 pages, late

Heteroreceptor complexes and their allosteric receptor-receptor interactions in the central nervous system. Focus on examples from Dopamine D2 and Serotonin 5-HT1a receptors

GPCR interacting proteins (specially β- arrestin) and their receptor-protein interactions are also covered but their interactions with the allosteric receptor-receptor interactions in heteroreceptor complexes remain to be elucidated. The physiological and pathological relevance of the allosteric receptor-receptor interactions in heteroreceptor complexes is emphasized and novel strategies for treatment of mental and neurological disease are introduced based on this new biological principle of integration. This work gives further experimental evidences which strongly support the current view that allosteric receptor–receptor interactions in heteroreceptor complexes appear to represent a new principle in biology making possible integration of signals already at the level of the plasma membrane. These heteroreceptor complexes and their dynamics may be part of the molecular basis of learning and memory. The receptor protomers and their allosteric receptor-receptor interactions can be disturbed in neurological and mental disorders, and in diseases of peripheral tissues like the endocrine, cardiovascular and immune systems. The dopamine (DA) neuron system most relevant for schizophrenia and Parkinson s diseases is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions as well as the dorsal striatum. The field of dopamine D2Rs changed significantly with the discovery of many types of D2R heteroreceptor complexes in the ventral and dorsal striatum. The results indicate that the D2R is a hub receptor (www.gpcr-hetnet.com) which interacts not only with many other GPCRs including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2R heteroreceptor complexes may contribute to the development of schizophrenia and Parkinson s diseases through changes in the balance of diverse D2R homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal GABA pathway. In schizophrenia, this will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Allosteric receptor-receptor interactions in GPCR heteromers appeared to introduce an intermolecular allosteric mechanism contributing to the diversity and bias in the GPCR protomers. In A2A-D2R heteroreceptor complexes allosteric A2A-D2R receptor-receptor interaction brings about a biased modulation of the D2R protomer signalling (Chapter 1). A conformational state of the D2R is induced which moves away from Gi/o signaling and instead favours b-arrestin2 mediated signalling which may be the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2AR-D2R heteroreceptor complexes. Furthermore, D2R-NTS1R heterocomplexes also exist in the ventral and dorsal striatum (Chapter 2) and likely also in midbrain DA nerve cells as D2R-NTS1R autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively. D2R protomer appeared to bias the specificity of the NT orthosteric binding site towards neuromedin N vs neurotensin in the heteroreceptor complex. There is a new awareness that Receptor tyrosine kinases (RTK) and transmitter activated GPCR possess the capacity for transactivation not only via GPCR induced release of neurotrophic factors, but also during signal initiation and propagation, using shared signaling pathways or using themselves as signaling platforms via direct allosteric receptor–receptor interactions. RTK are a family of transmembrane- spanning receptors that mediate the signaling from ligands such as growth factors, like the platelet-derived growth factor (PDGF), epidermal growth factor (EGF), the brain derived neurotrophic factor (BDNF), and the fibroblast growth factor (FGF). This hypothesis on direct GPCR-RTK receptor-receptor interactions in heteroreceptor complexes was introduced by Fuxe et al 1983. They also proposed the existence of 5- HT1A-FGFR1 heteroreceptor complexes having a role in depression. The hypothesis was introduced that the neurotrophic system FGF-2/FGFR1 may be a good candidate to mediate antidepressant induced improvement in 5-HT neuronal communication and neurotrophism with regeneration of connections lost during depression. RTK transactivation in response to antidepressant drug treatment was postulated to take place via a new allosteric receptor–receptor between distinct serotonin receptor subtypes and FGFR1 in heteroreceptor complexes. The discovery of brain FGFR1-5-HT1A heteroreceptor complexes and their enhancement of neuroplasticity offers an integration of the serotonin and the neurotrophic factor hypotheses of depression at the molecular level. These heteroreceptor complexes were found in the hippocampus and midbrain raphe 5-HT nerve cells, enriched in 5-HT1A autoreceptors. Based on the triplet puzzle theory several sets of triplet homologies were identified that may be part of the receptor interface. Combined FGF-2 and 5-HT1A agonist treatment increased the formation of these heterocomplexes and the facilitatory allosteric receptor-receptor interactions within them leading to an enhancement of FGFR1 signaling (Chapter 3). This integrative phenomenon is reciprocal and RTK signaling can be placed downstream of GPCRs. Formation of such heterocomplexes involving two major classes of membrane receptors can be involved in regulating all aspects of receptor protomer function including recognition, signaling, trafficking, desensitization, and downregulation (Chapter 3). These events were associated with development of rapid antidepressant effects. These heteroreceptor complexes are a novel target for antidepressant drugs. These examples, based on solid experimental evidences, serve to illustrate that allosteric receptor-receptor interactions in GPCR heteroreceptor complexes play a significant role in receptor diversity and bias of the participating GPCR protomers.G-protein coupled receptors (GPCR)-mediated signalling is a more complicated process than described previously since every GPCR and GPCR heteromer requires a set of G protein interacting proteins (GIP) which interacts with the receptor in an orchestrated spatio-temporal fashion. Therefore, there is a high interest in understanding the dynamics of the receptor-receptor and receptor-protein interactions in space and time, and specially, their integration in GPCR heterocomplexes of the Central Nervous System (CNS). Also, pathological protein-protein interactions in homocomplexes and heterocomplexes of Aβ, Tau, and α-Syn are at the heart of the development of conformational protein disorders. Along this work, experimental evidences are given to illustrate that GPCR interactions have relevance for neurological and mental diseases and are targets for drug development. GPCR containing heteromers and higher order heteromers through allosteric receptor- receptor interactions have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. They have become exciting new targets for neurotherapeutics in e.g. Parkinson’s disease, schizophrenia, drug addiction, anxiety and depression opening up a new field in neuropsychopharmacology. Along this work, the allosteric receptor-receptor interactions over the interfaces in A2AR-D2R, D2R-NTS1R, D2R-Sigma1R and 5-HT1A-FGFR1 heteroreceptor complexes will be explored and their biochemical, pharmacological and functional integrative implications in the CNS described. Methodologies for studies on receptor- receptor interactions are discussed including the use of FRET and BRET-based techniques in the analysis of G protein coupled receptor (GPCR) dimerization in living cells. In situ proximity ligation assay is performed to establish the existence of native heteroreceptor complexes in the CNS

Trialogue between Heidegger, Nietzsche, and Nāgārjuna in Todtnauberg.

The following philosophical dialogue between three philosophers is a thought experiment like Einstein's. Martin Heidegger (1889-1976) is the most written about 20th century philosopher. Friedrich Nietzsche (1844-1900) is a critical thinker of the highest order, who proclaimed the death of God and is considered the last western metaphysician. He found Platonism everywhere. The Acharya Nagarjuna (2-3d century AD) is perhaps the greatest single Indian philosopher; he is considered the greatest Buddhist thinker after the Buddha himself. Nagarjuna although less famous than the other two philosopher, his audacious and unique eastern way of thinking may provide some fundamental solutions to Heidegger's and Nietzsche's stickler dilemmas; and their morass and entanglement in their western philosophical predicaments and knots. Should we say, Nagarjuna will act as cutting the Gordian Knot? Written in 2011

Market failure, government inefficiency, and optimal R&D policy

This paper presents a growth model that can explain the coexistence of intellectual property rights and R&D subsidies as a response to the presence of both market and government failures. The framework can also generate the observed positive correlation between these two policy tools

Convergence in a dynamic Heckscher–Ohlin model with land

Convergence among nations that share the same preferences and technologies is a key result of the closed-economy neoclassical growth framework that has received substantial support in the data. However, Heckscher–Ohlin versions of the two-sector neoclassical growth model predict that nations that differ in their capital–labor ratios may not converge to the same steady state, even if they are identical in all other aspects. This is a puzzling result that warns us about potential dangers of international trade. In this paper we show that when land, an input in fixed supply, is introduced into the model, international trade in goods no longer limits the capacity of poor nations to catch up with the advanced world

Testing Capital-Skill Complementarity Across Sectors in a Panel of Spanish Regions

The aim of this paper is to examine the evidence for capital-skilled labor complementarity in six different activity sectors using aggregate production function specifications and a time-series, cross-section panel of Spanish regions. Estimation results have troubles finding evidence that supports departing from the Cobb-Douglas assumption and, if anything, find capital skill substitutablity in most sectors. They also suggest that capital skill complementarity might be a sector-specific phenomenon. El objetivo de este artículo es examinar la evidencia sobre la hipótesis capital-habilidad en seis diferentes sectores de actividades usando funciones de producción agregada en un panel de regiones españolas. Los resultados de la estimación tienen problemas para encontrar evidencia que apoye el separarse del supuesto Cobb-Douglas y, si acaso, encuentran substituibilidad entre el capital y la mano de obra cualificada en la mayoría de los sectores. También sugieren que la complementariedad capital-habilidad puede ser un fenómeno específico a ciertos sectores.Complementariedad de los inputs, funciones de producción agregada, datos de panel. Input complementarity, aggregate production function, panel data.

Answer the question: What is Enlightenment?

English translation of Kant's Beantwortung der Frage: Was ist Aufklärung? (Königsberg in Prussia, 30 September 1784)

Wright tariffs in the spanish electricity industry: The case of residential consumption.

This paper develops a capacity price model for the Spanish electricity industry and presents utilization level tariffs as an example of duration tariffs (Wright tariffs) when duration is aproximated by the ratio of consumption to power used. With this model and with the data on residential consumption of electricity several optimal t\\'o part tariffs for the residential level of utilization considering several hypothesis on the configuration of the generating equipment are computed. This allows for the estimation of the degree of optimality of the current tariff and to obtain an aproximation of efficiency losses caused by the existing regulatory regime.Capacity princing; Wright tariffs; Residential electricity;

Vortex solutions of an Abelian Higgs model with visible and hidden sectors

We study vortex solutions in a theory with dynamics governed by two weakly coupled Abelian Higgs models, describing a hidden sector and a visible sector. We analyze the radial dependence of the axially symmetric solutions constructed numerically and discuss the stability of vortex configurations for different values of the model parameters, studying in detail vortex decay into lower energy configurations. We find that even in a weak coupling regime vortex solutions strongly depend on the parameters of both the visible and hidden sectors. We also discuss on qualitative grounds possible implications of the existence of a hidden sector in connection with superconductivity.Comment: 22 pages, 10 figures, version accepted in JHE