Are there communicative intentions?

Grice in pragmatics and Levelt in psycholinguistics have proposed models of human communication where the starting point of communicative action is an individual intention. This assumption, though, has to face serious objections with regard to the alleged existence of explicit representations of the communicative goals to be pursued. Here evidence is surveyed which shows that in fact speaking may ordinarily be a quite automatic activity prompted by contextual cues and driven by behavioural schemata abstracted away from social regularities. On the one hand, this means that there could exist no intentions in the sense of explicit representations of communicative goals, following from deliberate reasoning and triggering the communicative action. On the other hand, however, there are reasons to allow for a weaker notion of intention than this, according to which communication is an intentional affair, after all. Communicative action is said to be intentional in this weaker sense to the extent that it is subject to a double mechanism of control, with respect both to present-directed and future-directed intentions

High-power collective charging of a solid-state quantum battery

Quantum information theorems state that it is possible to exploit collective quantum resources to greatly enhance the charging power of quantum batteries (QBs) made of many identical elementary units. We here present and solve a model of a QB that can be engineered in solid-state architectures. It consists of $N$ two-level systems coupled to a single photonic mode in a cavity. We contrast this collective model ("Dicke QB"), whereby entanglement is genuinely created by the common photonic mode, to the one in which each two-level system is coupled to its own separate cavity mode ("Rabi QB"). By employing exact diagonalization, we demonstrate the emergence of a quantum advantage in the charging power of Dicke QBs, which scales like $\sqrt{N}$ for $N\gg 1$.Comment: 8 pages, 5 figures. Version v2 supersedes version v1 where a technical mistake was done in using the Holstein-Primakoff transformation. The quantum advantage in the maximum charging power discussed in version v1 has been found to be robust. We have also updated the list of author

A novel suicide gene therapy for the treatment of p16-overexpressing tumors

p16Ink4ais a potent cell cycle inhibitor engaged to support cell cycle arrest during cellular senescence. However, in tumors carrying mutations in key downstream effectors, p16Ink4ais highly expressed but fails to block cell proliferation. p16Ink4a-overexpressing tumor cells are highly aggressive and no targeted interventions are available. To study the effect of specific therapies, we generated murine sarcomas by overexpressing RAS oncogene and disrupting p53 activity. We observed that p16Ink4a-overxpressing murine sarcoma cells were resistant to ABT-263 and ABT-737, anti-cancer small molecules previously shown to eliminate p16Ink4a+senescent cells. We then generated sarcoma cells carrying a suicide and reporter gene, called 3MR, under the regulation of the full p16Ink4apromoter. Activation of the suicide efficiently killed p16Ink4a-overxpressing sarcoma cellsin vitroandin vivo. These data suggest that suicide gene therapy could represent an important therapeutic approach for the treatment of highly aggressive p16Ink4a+cancers

Gesti co-verbali e immagini mentali: i confini dell’intenzione comunicativa

Riassunto: Le immagini mentali sono parte delle intenzioni comunicative veicolate negli scambi verbali, e dunque del significato inteso dal parlante (Grice)? Questioni simili sono state dibattute con riferimento al paradigma dell’embodiment. Qui intendiamo muoverci su un terreno differente: il dominio dei gesti, con particolare riferimento a quelli rappresentativi, caratterizzati dallo stretto rapporto con le rappresentazioni senso-motorie delle azioni. La linea argomentativa sarà dunque bipartita. Innanzitutto, intendiamo mostrare che i gesti contribuiscono a determinare l’intenzione comunicativa, come è evidente in casi nei quali il parlante si impegna in modo manifesto a renderli salienti – ma qui sarà anche importante l’osservazione che l’intenzione comunicativa non va identificata con una preliminare pianificazione cosciente. In secondo luogo, argomenteremo che il contributo dei gesti all’intenzione comunicativa è genuinamente imagistic, non proposizionale. In particolare, esamineremo due argomenti solitamente presentati come a favore dell’ipotesi proposizionale: che le immagini non possono essere parte dell’intenzione comunicativa, rispettivamente, perché non portano un contenuto giudicabile in termini di vero/falso, e perché non consentono di effettuare inferenze. Vedremo che entrambe le argomentazioni sono discutibili.Parole chiave: Intenzione comunicativa; Gesti rappresentativi; Imagery; Significato del parlante Co-verbal Gestures and Mental Images: The Borders of Communicative Intentions Abstract: Do mental images form part of a speaker’s communicative intention? This and similar questions have usually been addressed within the framework of embodied cognition. Here, instead, we want to address the question from a different point of view, examining representational gestures, which are characterised by their strong relationship to sensory-motor representations. For this reason, our argument takes two directions. First, we show that representational gestures can form part of a speaker’s communicative intention as, for example, when the speaker overtly makes them salient. However, it is important to point out that being part of a communicative intention is not equivalent to being consciously planned. Secondly, we will argue that the meaning carried by gestures is actually imagistic, and not propositional. To this end, we provide a detailed discussion of two arguments favouring the propositional hypothesis: that images cannot be part of the speaker’s communicative intention because their content is not truth-conditional and because they do not allow us to make inferences. We will show that both these arguments are debatable.Keywords: Communicative Intentions; Representational Gestures; Imagery; Speaker’s Meanin

A model for the blood-brain barrier and its application in modeling metastasis to the brain

The blood-brain barrier (BBB) is known to be one of the least permeable portions of the vascular system, serving to protect the central nervous system from agents deleterious to the brain while also preventing or limiting the passage of drugs to treat neurological diseases. Despite this, the brain is recognized to be one of the primary sites of metastasis, especially for lung and breast cancers. While animal experiments have proven useful, realistic models of the BBB using human cells are limited and remain a subject of intense research. Work over the past several years has led to several promising systems, although it has proven difficult to achieve levels of permeability comparable to those observed in vivo. We have recently sought to develop several systems, first with a mixture of primary rat and human cells (Adriani et al., 2017), and more recently, a model based entirely on human cells. This latter system relies on self-assembly of three critical cell types: human iPSC-derived endothelial cells, primary brain pericytes, and primary brain astrocytes. When suspended in a fibrinogen and thrombin gel solution and introduced to a microfluidic platform, the cells organize into a microvascular network in direct physical contact with pericytes and astrocyte end-feet. Over 7 days, the network forms and attains a relatively stable state that permits perfusion from the side channels of the device. Once formed, the vascular network is characterized by immunofluorescent imaging, RT-PCR analysis, and functional measures such as permeability to fluorescent probes of various molecular weights. In comparing the networks as they increase in cellular complexity from endothelial cells alone, to ECs and pericytes, and finally, ECs, PCs and astrocytes, the expression of basement membrane and junctional proteins is seen to increase. Simultaneously, the network permeability is observed to progressively fall, indicating improved barrier function. Permeability values for a 10 kDa FITC-dextran are found to be comparable to those measured in the rat brain. Preliminary experiments have been conducted to determine the rates of extravasation of circulating tumor cells past the model BBB. These experiments introduce breast cancer cells (MDA-MB-231) into the microvascular network with the flow of medium where they adhere to the endothelium or arrest due to physical trapping. Once immobilized, the cells are observed over time to quantify their tendency to undergo transendothelial migration. Results show that as the CTCs are increasingly invasive as the system complexity increases (mono-culture to tri-culture), opposite to what would be expected if tumor cells follow the trend of permeability. Studies are currently underway to understand the cell-cell interactions that give rise to this counterintuitive behavior. Reference: Adriani, G., Ma, D., Pavesi, A., Kamm, R. D., & Goh, E. L. K. (2017). A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood–brain barrier. Lab on a Chip, 17 (12), 2067-2075 Acknowledgements: This work was supported by an Ermenegildo Zegna Founder’s scholarship, an MIT-POLITO grant (BIOMODE - Compagnia di San Paolo), the Cure Alzheimer\u27s Fund, the Japan Society for the Promotion of Science, the US National Science Foundation (CBET-0939511), the National Cancer Institute (U01 CA202177), and an MIT and POLITO MITOR project (NANOCAB)

In vitro models of molecular and nano-particle transport across the blood-brain barrier

The blood-brain barrier (BBB) is the tightest endothelial barrier in humans. Characterized by the presence of tight endothelial junctions and adherens junctions, the primary function of the BBB is to maintain brain homeostasis through the control of solute transit across the barrier. The specific features of this barrier make for unique modes of transport of solutes, nanoparticles, and cells across the BBB. Understanding the different routes of traffic adopted by each of these is therefore critical in the development of targeted therapies. In an attempt to move towards controlled experimental assays, multiple groups are now opting for the use of microfluidic systems. A comprehensive understanding of bio-transport processes across the BBB in microfluidic devices is therefore necessary to develop targeted and efficient therapies for a host of diseases ranging from neurological disorders to the spread of metastases in the brain

In Vitro Microfluidic Models for Neurodegenerative Disorders

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease- on-a-chip models focusing on Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps