El concepto de Movimiento en el Compendium filosófico de Jacques Legrand

The following paper investigates the concept of motion in Jacques Legrand, a hitherto little-studied author of the early fifteenth century. Legrand, an important member of the Order of Hermits of Saint Augustine, wrote a philosophical Compendium for the students of his Order. This contribution first attempts to provide a contextualization of Legrand’s treatment of motion within this work. Legrand’s contribution to philosophical encyclopedism is here discussed. Secondly, it reviews the most important theories on the nature of movement in the Middle Ages. Thirdly, it offers a detailed analysis of Legrand’s arguments in support of the nominalist view that it is unnecessary (if not wrong) to consider the local motion as a fluxus added to the moveable body. The article suggests that Legrand’s generalized nominalist position may be connected with certain lines to be followed within his own Order or even with the anti-realist ideology of the conciliarists philosopher, like Pierre D’Ailly and Jean Gerson.El siguiente artículo investiga el concepto de movimiento en Jacques Legrand, un autor de principios del siglo XV hasta ahora poco estudiado. Legrand, miembro importante de la Orden de los Ermitaños de San Agustín, escribió un compendio filosófico para los estudiantes de su Orden. Esta contribución intenta en primer lugar proporcionar una contextualización del tratamiento del problema del movimiento llevado a cabo por Legrand en su Compendium. Aquí se discute la contribución de Legrand al enciclopedismo filosófico. En segundo lugar, se revisan las teorías más importantes sobre la naturaleza del movimiento en la Edad Media. En tercer lugar, se ofrece un análisis detallado de los argumentos de Legrand en apoyo de la visión nominalista según la cual es innecesario (si no erróneo) considerar el movimiento local como un fluxus añadido al cuerpo en movimiento. El artículo sugiere que la posición nominalista generalizada de Legrand puede estar conectada con ciertas líneas a seguir dentro de su propio orden o incluso con la ideología antirrealista de los filósofos conciliaristas, como Pierre D’Ailly y Jean Gerson

The Writings of Nicole Oresme: A Systematic Inventory

This paper provides an up-to-date inventory of the works of Nicole Oresme (ca. 1320–1382). For each text, we present the incipit and the explicit, its (approximate) date, the list of manuscripts, and, whenever possible, editions and translations. We also inventory self-references contained in Oresme's writings and discuss specific problems concerning their titles, attributions, and textual transmission. Oresme's works are classified into nine groups, for each of which we offer preliminary remarks to situate the group in the context of Oresme's career. The two appendices provide detailed information about two texts of possible Oresmian attribution

Less Empathic and More Reactive: The Different Impact of Childhood Maltreatment on Facial Mimicry and Vagal Regulation

Facial mimicry and vagal regulation represent two crucial physiological responses to others' facial expressions of emotions. Facial mimicry, defined as the automatic, rapid and congruent electromyographic activation to others' facial expressions, is implicated in empathy, emotional reciprocity and emotions recognition. Vagal regulation, quantified by the computation of Respiratory Sinus Arrhythmia (RSA), exemplifies the autonomic adaptation to contingent social cues. Although it has been demonstrated that childhood maltreatment induces alterations in the processing of the facial expression of emotions, both at an explicit and implicit level, the effects of maltreatment on children's facial mimicry and vagal regulation in response to facial expressions of emotions remain unknown. The purpose of the present study was to fill this gap, involving 24 street-children (maltreated group) and 20 age-matched controls (control group). We recorded their spontaneous facial electromyographic activations of corrugator and zygomaticus muscles and RSA responses during the visualization of the facial expressions of anger, fear, joy and sadness. Results demonstrated a different impact of childhood maltreatment on facial mimicry and vagal regulation. Maltreated children did not show the typical positive-negative modulation of corrugator mimicry. Furthermore, when only negative facial expressions were considered, maltreated children demonstrated lower corrugator mimicry than controls. With respect to vagal regulation, whereas maltreated children manifested the expected and functional inverse correlation between RSA value at rest and RSA response to angry facial expressions, controls did not. These results describe an early and divergent functional adaptation to hostile environment of the two investigated physiological mechanisms. On the one side, maltreatment leads to the suppression of the spontaneous facial mimicry normally concurring to empathic understanding of others' emotions. On the other side, maltreatment forces the precocious development of the functional synchronization between vagal regulation and threatening social cues facilitating the recruitment of fight-or-flight defensive behavioral strategies

Pressure pulsation in Kaplan turbines: Prototype-CFD comparison

Abstract. Pressure pulsation phenomena in a large Kaplan turbine are investigated by means of numerical simulations (CFD) and prototype measurements in order to study the dynamic behavior of flow due to the blade passage and its interaction with other components of the turbine. Numerical simulations are performed with the commercial software Ansys CFX code, solving the incompressible Unsteady Reynolds-Averaged-Navier Stokes equations under a finite volume scheme. The computational domain involves the entire machine at prototype scale. Special care is taken in the discretization of the wicket gate overhang and runner blade gap. Prototype measurements are performed using pressure transducers at different locations among the wicket gate outlet and the draft tube inlet. Then, CFD results are compared with temporary signals of prototype measurements at identical locations to validate the numerical model. A detailed analysis was focused on the tip gap flow and the pressure field at the discharge ring. From a rotating reference frame perspective, it is found that the mean pressure fluctuates accordingly the wicket gate passage. Moreover, in prototype measurements the pressure frequency that reveals the presence of modulated cavitation at the discharge ring is distinguished, as also verified from the shape of erosion patches in concordance with the number of wicket gates

Drosophila mutant model of Parkinson's disease revealed an unexpected olfactory performance: Morphofunctional evidences

Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatment

Impaired sense of smell in a Drosophila Parkinson's model.

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster 32 is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments

Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1(B9) Drosophila melanogaster Genetic Model of Parkinson's Disease

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3–6 (I), 10–15 (II) and 20–25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment

Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles

Background: Triple-negative breast cancer (TNBC) is a very heterogeneous disease. Several gene expression and mutation profiling approaches were used to classify it, and all converged to the identification of distinct molecular subtypes, with some overlapping across different approaches. However, a standardised tool to routinely classify TNBC in the clinics and guide personalised treatment is lacking. We aimed at defining a specific gene signature for each of the six TNBC subtypes proposed by Lehman et al. in 2011 (basal-like 1 (BL1); basal-like 2 (BL2); mesenchymal (M); immunomodulatory (IM); mesenchymal stem-like (MSL); and luminal androgen receptor (LAR)), to be able to accurately predict them. Methods: Lehman’s TNBCtype subtyping tool was applied to RNA-sequencing data from 482 TNBC (GSE164458), and a minimal subtype-specific gene signature was defined by combining two class comparison techniques with seven attribute selection methods. Several machine learning algorithms for subtype prediction were used, and the best classifier was applied on microarray data from 72 Italian TNBC and on the TNBC subset of the BRCA-TCGA data set. Results: We identified two signatures with the 120 and 81 top up- and downregulated genes that define the six TNBC subtypes, with prediction accuracy ranging from 88.6 to 89.4%, and even improving after removal of the least important genes. Network analysis was used to identify highly interconnected genes within each subgroup. Two druggable matrix metalloproteinases were found in the BL1 and BL2 subsets, and several druggable targets were complementary to androgen receptor or aromatase in the LAR subset. Several secondary drug–target interactions were found among the upregulated genes in the M, IM and MSL subsets. Conclusions: Our study took full advantage of available TNBC data sets to stratify samples and genes into distinct subtypes, according to gene expression profiles. The development of a data mining approach to acquire a large amount of information from several data sets has allowed us to identify a well-determined minimal number of genes that may help in the recognition of TNBC subtypes. These genes, most of which have been previously found to be associated with breast cancer, have the potential to become novel diagnostic markers and/or therapeutic targets for specific TNBC subsets

p 53 abnormal expression might influence global outcome through egfr modulation in ras braf wild type metastatic colorectal cancer patients receiving later line irinotecan cetuximab

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