Sergio Fonda

Predictive mechanisms in idiom comprehension

Prediction is pervasive in human cognition and plays a central role in language comprehension. At an electrophysiological level, this cognitive function contributes substantially in determining the amplitude of the N400. In fact, the amplitude of the N400 to words within a sentence has been shown to depend on how predictable those words are: The more predictable a word, the smaller the N400 elicited. However, predictive processing can be based on different sources of information that allow anticipation of upcoming constituents and integration in context. In this study, we investigated the ERPs elicited during the comprehension of idioms, that is, prefabricated multiword strings stored in semantic memory. When a reader recognizes a string of words as an idiom before the idiom ends, she or he can develop expectations concerning the incoming idiomatic constituents. We hypothesized that the expectations driven by the activation of an idiom might differ from those driven by discourse-based constraints. To this aim, we compared the ERP waveforms elicited by idioms and two literal control conditions. The results showed that, in both cases, the literal conditions exhibited a more negative potential than the idiomatic condition. Our analyses suggest that before idiom recognition the effect is due to modulation of the N400 amplitude, whereas after idiom recognition a P300 for the idiomatic sentence has a fundamental role in the composition of the effect. These results suggest that two distinct predictive mechanisms are at work during language comprehension, based respectively on probabilistic information and on categorical template matching.

Computer-assisted analyses of [14C]2-DG autoradiographs employing a general purpose image processing system

A general purpose image processing system is described including B/W TV camera, high resolution image processor and display system (TESAK VDC 501), computer (DEC PDP 11/23), and monochrome and color monitors. Images may be acquired from a microscope equipped with a TV camera or using the TV in direct viewing; the A/D converter and the image processor provides fast (40 ms) and precise (512 X 512 data points) digitization of TV signal with a 256 gray levels maximum resolution. Computer programs have been developed in order to perform qualitative and quantitative analyses of autoradiographs obtained with the 2-DG method, which are written in FORTRAN and MACRO 11 Assembly Language. They include: (1) procedures designed to recognize errors in acquisition due to possible image shading and correct them via software; (2) routines suitable for qualitative analyses of the whole image or selected regions of it, providing the opportunity for pseudocolor coding, statistics, graphic overlays; (3) programs permitting the conversion of gray levels into metabolic rates of glucose utilization and the display of gray- or color-coded metabolic maps.

Cloze probability does not only affect N400 amplitude: The case of complex prepositions

Cloze-probability levels are inversely correlated with N400 amplitude, indicating an easier integration for expected words in semantic-pragmatic contexts. Here we exploited the prespecified standard order of complex prepositions and measured the ERPs time-locked to the last preposition in sentences in which complex prepositions were presented in their standard form or with the last preposition changed. The expected preposition elicited an N280 followed by an N400-700, two ERP components previously associated to the processing of closed-class words. The unexpected preposition elicited only an N280, and the N400-700 was reduced. These results reflect the specificity of the contextual constraints linked to the complex preposition word sequence.

Combining Near-Infrared Spectroscopy and Electroencephalography to Monitor Brain Function

We propose to embed a continuous-wave near-infrared spectroscopy system within an electroencephalography system to perform functional hemodynamic and neural response simultaneously. In this study, we present the measuring system and the results consisting in changes of oxyhemoglobin and deoxyhemoglobin derived from continuous-wave near-infrared spectroscopy data and the evoked potential responses derived from the electroencephalography recordings. A checkerboard stimulus was adopted to elicit a response signal from the visual cortex. The results collected demonstrate that near infrared spectroscopy can detect task-induced changes in homodynamic

DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM).

Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples.

Advanced learning and ICT: new teaching experiences in university setting

The digital board is thought of as a tool that has limited use, primary or secondary school or in a situation of learning for the handicapped. This case study aims to show how these new tools can be used in for higher learning, in scientific and technical universities. The current software available on the market and its use with these tools foresees originality in the approach to teaching in the future. The article explores the use of advanced innovative technology in the lecture hall for effective teaching and learning. The digital whiteboard tool is a flexible and powerful didactic instrument that can greatly enrich the experience of both the learner and the lecturer. This article will explore a completed case study, a case study still in progress and future possibilities.

The commissural transfer of the horizontal optokinetic signal in the rat: a c-Fos study.

We applied the Fos method in rats subjected to horizontal optokinetic stimulation (OKS) to study whether optokinetic information is transferred through the commissural pretectal fibres from one optic tract nucleus (NOT) to the opposite. In binocular as well as in monocular nasalward OKS, the highest Fos immunoreactivity was found in the NOT contralateral to the nasalward stimulation, as expression of the activation either of direction-selective cells and of commissural neurons. Even the opposite NOT showed many Fos-positive cells activated by the opposite nucleus throughout the commissural pretectal pathway. They might be the GABA positive cells, which are thought to allow the activation in one nucleus to be transformed into inhibition of the opposite side. In monocular temporalward OKS, the inhibition on direction-selective cells and the consequent silencing of commissural neurons caused the faint immunoreactivity in the NOT contralateral to eye stimulated. In the opposite nucleus the few Fos-positive cells emerged as a consequence of the lack of the normal tonic commissurally mediated inhibition.

Functional cerebral activation detected by an integrated system combining CW-NIR spectroscopy and EEG

The aim of this study is to explore the possibility of correlating hemodynamic changes and neural activities in the brain by using an integrated system combining Near Infrared Spectroscopy (NIRS) and electroencephalographic activity (EEG). We present brain hemodynamic changes and EEG recordings obtained from four volunteers during the performance of two different sequential thumb-finger opposition tasks, with and without a related mental activity. The optical and electrical signals were recorded simultaneously on the subject forehead. The coupling of the two systems could be useful to demonstrate correlation between cognitive paradigms and hemodynamic signals.

Conformational Propensity and Biological Studies of Proline Mutated LR Peptides Inhibiting Human Thymidylate Synthase and Ovarian Cancer Cell Growth

LR and [d-Gln4]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro n]-peptides. [Pro3]LR and [Pro4]LR show improved cell growth inhibition and similar intracellular protein modulation compared with LR. These represent a step forward to the identification of more rigid and metabolically stable peptides.

Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers.

Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes (BRCA1, MGMT, and MLH1), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of MGMT, OSMR, ESR1, and FOXL2 and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.