Phase behavior of the Confined Lebwohl-Lasher Model

The phase behavior of confined nematogens is studied using the Lebwohl-Lasher model. For three dimensional systems the model is known to exhibit a discontinuous nematic-isotropic phase transition, whereas the corresponding two dimensional systems apparently show a continuous Berezinskii-Kosterlitz-Thouless like transition. In this paper we study the phase transitions of the Lebwohl-Lasher model when confined between planar slits of different widths in order to establish the behavior of intermediate situations between the pure planar model and the three-dimensional system, and compare with previous estimates for the critical thickness, i.e. the slit width at which the transition switches from continuous to discontinuous.Comment: Submitted to Physical Review

Automated Synthesis of Tableau Calculi

This paper presents a method for synthesising sound and complete tableau calculi. Given a specification of the formal semantics of a logic, the method generates a set of tableau inference rules that can then be used to reason within the logic. The method guarantees that the generated rules form a calculus which is sound and constructively complete. If the logic can be shown to admit finite filtration with respect to a well-defined first-order semantics then adding a general blocking mechanism provides a terminating tableau calculus. The process of generating tableau rules can be completely automated and produces, together with the blocking mechanism, an automated procedure for generating tableau decision procedures. For illustration we show the workability of the approach for a description logic with transitive roles and propositional intuitionistic logic.Comment: 32 page

Correlations in the low-temperature phase of the two-dimensional XY model

Monte Carlo simulations of the two-dimensional XY model are performed in a square geometry with fixed boundary conditions. Using a conformal mapping it is very easy to deduce the exponent eta_sigma(T) of the order parameter correlation function at any temperature in the critical phase of the model. The temperature behaviour of eta_sigma(T) is obtained numerically with a good accuracy up to the Kosterlitz-Thouless transition temperature. At very low temperatures, a good agreement is found with Berezinskii's harmonic approximation. Surprisingly, we show some evidence that there are no logarithmic corrections to the behaviour of the order parameter density profile (with symmetry breaking surface fields) at the Kosterlitz-Thouless transition temperature.Comment: 7 pages, 2 eps figure

A Reciprocal Cell–Cell Interaction Mediated by NT-3 and Neuregulins Controls the Early Survival and Development of Sympathetic Neuroblasts

Neurotrophin 3 (NT-3) can support the survival of some embryonic sympathetic neuroblasts before they become nerve growth factor dependent. We show that NT-3 is produced in vivo by nonneuronal cells neighboring embryonic sympathetic ganglia. NT-3 mRNA is produced by these nonneuronal cells in vitro and is up-regulated by platelet-derived growth factor, ciliary neurotrophic factor, and glial growth factor 2 (a neuregulin). Nonneuronal cell–conditioned medium promotes survival and induces TrkA expression in isolated sympathetic neuroblasts, and this activity is blocked by anti-NT-3 antibody. Neuroblasts also enhance NT-3 production by nonneuronal cells. Neuroblasts synthesize several forms of neuregulin, and antibodies to neuregulin attenuate the effect of the neuroblasts on the nonneuronal cells. These data suggest a reciprocal cell–cell interaction, in which neuroblast-derived neuregulins promote NT-3 production by neighboring nonneuronal cells, which in turn promotes neuroblast survival and further differentiation

Topological transition in a two-dimensional model of liquid crystal

Simulations of nematic-isotropic transition of liquid crystals in two dimensions are performed using an O(2) vector model characterised by non linear nearest neighbour spin interaction governed by the fourth Legendre polynomial $P\_4$. The system is studied through standard Finite-Size Scaling and conformal rescaling of density profiles of correlation functions. A topological transition between a paramagnetic phase at high temperature and a critical phase at low temperature is observed. The low temperature limit is discussed in the spin wave approximation and confirms the numerical results

Immunometabolism modulation in therapy

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions

Gramática y escritura. La aplicación de la teoría gramatical a la enseñanza y corrección de problemas de escritura. El caso de la coma

Este trabajo explora la estrecha relación que existe entre la gramática y los signos de puntuación, con el fin de demostrar que, haciendo visible dicha conexión en la enseñanza de la escritura, se pueden solventar y corregir muchos de los errores que se comenten de manera mucho más efectiva. Ya que dicha relación se presenta, en muchos casos, de manera tangencial (o directamente se ignora), el objetivo del presente TFG es particularmente relevante. Para ello, se emplea el caso concreto de la coma (,), mediante el cual se analiza si las recomendaciones ortográficas tienen o no una base gramatical en la que sustentar la normativa: si la tienen, cómo se defiende. Se abre un escenario en el que la dimensión instrumental de la lengua (la escritura) se comunique de manera natural y efectiva con su dimensión teórica (la gramática).En aquest treball s'explora la estreta relació que existeix entre la gramàtica y els signes de puntuació, amb l'objectiu de demostrar que, fent visible aquesta connexió a l'ensenyament de l'escriptura, es poden resoldre y corregir molts dels errors que es cometen de manera més efectiva. Ja que aquesta relació és presentada, en molts casos, de manera tangencial (o directament s'ignora), l'objectiu del present TFG és particularment rellevant. Per això, s'utilitza el cas concret de la coma (,), amb el qual s'analitza si les recomanacions ortogràfiques tenen o no una base gramatical en la que sustentar la normativa: si la tenen, com es defensa. S'obre un escenari en què la dimensió instrumental de la llengua (la escriptura) es comuniqui de manera natural i efectiva amb la seva dimensió teòrica (la gramàtica)

p27Kip1 regulates alpha-synuclein expression

Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson's disease and multiple system atrophy. However, the mechanisms involved in its transcriptional regulation are poorly understood. We investigated here the role of the cyclin-dependent kinase (Cdk) inhibitor and transcriptional regulator p27Kip1 (p27) in the regulation of α-SYN expression. We observed that selective deletion of p27 by CRISPR/Cas9 technology in neural cells resulted in increased levels of α-SYN. Knock-down of the member of the same family p21Cip1 (p21) also led to increased α-SYN levels, indicating that p27 and p21 collaborate in the repression of α-SYN transcription. We demonstrated that this repression is mediated by the transcription factor E2F4 and the member of the retinoblastoma protein family p130 and that it is dependent of Cdk activity. Chromatin immunoprecipitation analysis revealed specific binding sites for p27, p21 and E2F4 in the proximal α-SYN gene promoter. Finally, luciferase assays revealed a direct action of p27, p21 and E2F4 in α-SYN gene expression. Our findings reveal for the first time a negative regulatory mechanism of α-SYN expression, suggesting a putative role for cell cycle regulators in the etiology of synucleinopathies

Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives