Monsters begat by quantifiers?

It is common practice in formal semantics to assume that the context specifies an assignment of values to variables and that the same variables that receive contextually salient values when they occur free may also be bound by quantifiers and λs. These assumptions are at work to provide a unified account of indexical and bound uses of third person pronouns, namely an account by which the same lexical item is involved in both uses. One apparent consequence of this approach is that quantifiers and λs are monsters in Kaplan's sense. We argue that this consequence can, and should, be avoided. We explore an alternative unified account based on the idea that variable assignments occur both as coordinates of the context and as coordinates of the circumstance of evaluation. The outcome is a non indexical account of free third person pronouns and a new conception of the role and structure of assignment functions

Replica symmetric evaluation of the information transfer in a two-layer network in presence of continuous+discrete stimuli

In a previous report we have evaluated analytically the mutual information between the firing rates of N independent units and a set of multi-dimensional continuous+discrete stimuli, for a finite population size and in the limit of large noise. Here, we extend the analysis to the case of two interconnected populations, where input units activate output ones via gaussian weights and a threshold linear transfer function. We evaluate the information carried by a population of M output units, again about continuous+discrete correlates. The mutual information is evaluated solving saddle point equations under the assumption of replica symmetry, a method which, by taking into account only the term linear in N of the input information, is equivalent to assuming the noise to be large. Within this limitation, we analyze the dependence of the information on the ratio M/N, on the selectivity of the input units and on the level of the output noise. We show analytically, and confirm numerically, that in the limit of a linear transfer function and of a small ratio between output and input noise, the output information approaches asymptotically the information carried in input. Finally, we show that the information loss in output does not depend much on the structure of the stimulus, whether purely continuous, purely discrete or mixed, but only on the position of the threshold nonlinearity, and on the ratio between input and output noise.Comment: 19 pages, 4 figure

A theoretical model of neuronal population coding of stimuli with both continuous and discrete dimensions

In a recent study the initial rise of the mutual information between the firing rates of N neurons and a set of p discrete stimuli has been analytically evaluated, under the assumption that neurons fire independently of one another to each stimulus and that each conditional distribution of firing rates is gaussian. Yet real stimuli or behavioural correlates are high-dimensional, with both discrete and continuously varying features.Moreover, the gaussian approximation implies negative firing rates, which is biologically implausible. Here, we generalize the analysis to the case where the stimulus or behavioural correlate has both a discrete and a continuous dimension. In the case of large noise we evaluate the mutual information up to the quadratic approximation as a function of population size. Then we consider a more realistic distribution of firing rates, truncated at zero, and we prove that the resulting correction, with respect to the gaussian firing rates, can be expressed simply as a renormalization of the noise parameter. Finally, we demonstrate the effect of averaging the distribution across the discrete dimension, evaluating the mutual information only with respect to the continuously varying correlate.Comment: 20 pages, 10 figure

Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab

Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment.We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab.Seventy-two patients with histologically proven metastatic colorectal cancer, treated with Irinotecan and Cetuximab based chemotherapy, were eligible for our analysis.In metastases pAKT correlated with RR (9% vs. 58%, p\u2009=\u20090.004), PFS (2.3 months vs. 9.2 months p\u2009<\u20090.0001) and OS (6.1 months vs. 26.7 months p\u2009<\u20090.0001) and pMAPK correlated with RR (10% vs. 47%, p\u2009=\u20090.002), PFS (2.3 months vs. 8.6 months p\u2009<\u20090.0001) and OS (7.8 months vs. 26 months p\u2009=\u20090.0004). At multivariate analysis pAKT and pMAPK in metastases were able to independently predict PFS. pAKT in metastases independently correlated with RR as wellpAKT and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAKT and pMAPK metastases expression targeting these factors may be crucial

Mutual Guarantee Institutions (MGIs) and small business credit during the crisis

The recent economic and financial crisis has drawn attention to how mutual guarantee institutions (MGIs) facilitate small and medium enterprises in accessing bank financing. The aim of this paper is twofold. First, we describe the structural features of the Italian market for mutual guarantees and its significance for small business credit. To this end, we use extensive databases (the Central Credit Register and the Central Balance Sheet Register) as well as specific surveys, which allow us to fill information gaps about this industry and to quantify regional diversity. Second, we investigate whether MGIs’ support to small firms continued to be effective in 2008-09, when credit constraints to Italian firms peaked. We find that MGIs played a role in avoiding a break-up in credit flows to affiliated firms, which also benefited from a lower cost of credit. However, this came at the cost of a deterioration in credit quality, which was more intense for customers with guarantees from MGIs.microfinance, peer monitoring, small business finance

Cardiometabolic burden and biomarkers of autonomous cortisol secretion

The overwhelming majority of incidentally discovered adrenal tumours are benign adrenocortical tumours. These can be non-functioning (NFAT) or associated with autonomous cortisol secretion on a spectrum ranging from rare clinically overt adrenal Cushing’s syndrome (CS) to much more prevalent mild autonomous cortisol secretion (MACS) without signs of CS. Here I present the characteristics of a large cohort of persons with newly diagnosed benign adrenocortical tumours. In 1305 prospectively recruited cases, almost every second person with benign adrenocortical tumours was diagnosed with MACS. Persons with MACS had rates of cardiometabolic disease similar to CS, particularly increased prevalence and severity of hypertension and type 2 diabetes. Urine multi-steroid profiling of these persons revealed a gradual increase in glucocorticoid excretion from NFAT over MACS to CS, whilst androgen excretion decreased. Increased glucocorticoid and 11-oxygenated androgen metabolite excretion predicted clinical outcomes including hypertension, type 2 diabetes, and the presence of bilateral adrenal tumours. A representative group of 291 persons underwent untargeted serum metabolome profiling. Prototype-based supervised machine learning identified progressive metabolic changes in MACS and CS suggestive of lipotoxicity, dysfunctional lipid β-oxidation, and oxidative stress across the spectrum of autonomous cortisol secretion. These results show that MACS is a prevalent cardiometabolic risk condition associated with distinct changes in the steroid and untargeted metabolome. Observed changes offer the prospect of risk stratification of affected individuals