Identifying pathological biomarkers: histochemistry still ranks high in the omics era

In recent years, omic analyses have been proposed as possible approaches to diagnosis, in particular for tumours, as they should be able to provide quantitative tools to detect and measure abnormalities in gene and protein expression, through the evaluation of transcription and translation products in the abnormal vs normal tissues. Unfortunately, this approach proved to be much less powerful than expected, due to both intrinsic technical limits and the nature itself of the pathological tissues to be investigated, the heterogeneity deriving from polyclonality and tissue phenotype variability between patients being a major limiting factor in the search for unique omic biomarkers. Especially in the last few years, the application of refined techniques for investigating gene expression in situ has greatly increased the diagnostic/prognostic potential of histochemistry, while the progress in light microscopy technology and in the methods for imaging molecules in vivo have provided valuable tools for elucidating the molecular events and the basic mechanisms leading to a pathological condition. Histochemical techniques thus remain irreplaceable in pathologist's armamentarium, and it may be expected that even in the future histochemistry will keep a leading position among the methodological approaches for clinical pathology

Formation of waterfalls by intermittent burial of active faults

Waterfalls commonly exist near bounding faults of mountain ranges, where erosional bedrock catchments transition to depositional alluvial fans. We hypothesize that aggradation on alluvial fans can bury active faults, and that the faults accumulate slip in the subsurface to produce a bedrock scarp. Following entrenchment of the alluvial fan, the scarp can be exposed as a waterfall. To explore this hypothesis, we derived a geometric model for waterfall height that depends on alluvial fan length and the relative time scales of (1) tectonic uplift, (2) a forcing mechanism for cycles of fan aggradation and incision, and (3) a response of fan aggradation to changes in sediment flux. We find that the model is consistent with observations at Gower Gulch, Death Valley, California, where a man-made drainage capture event in 1941 caused rapid fan incision and exposed a waterfall at the canyon-fan transition. We also compared the model to 62 waterfalls in 18 catchments of the Death Valley area and found that at least 15 of the waterfalls are best explained by the fault-burial mechanism. Using field measurements of grain size and channel geometries, we show that the fault-burial mechanism can produce the observed waterfall heights, measuring 4−19 m, under a uniform climatic forcing scenario requiring variations of 20% in precipitation during the late Pleistocene. The fault-burial mechanism, through the creation of upstream propagating waterfalls, may allow catchment-fan systems to experience frequent cycles of enhanced erosion in catchments and deposition on fans that likely convolve tectonic and climatic signals

Corporate ownership structure and bank loan syndicate structure

Using a novel data set on corporate ownership and control, we show that the divergence between the control rights and cash-flow rights of a borrowing firm's largest ultimate owner has a significant impact on the concentration and composition of the firm's loan syndicate. When the control-ownership divergence is large, lead arrangers form syndicates with structures that facilitate enhanced due diligence and monitoring efforts. These syndicates tend to be relatively concentrated and composed of domestic banks that are geographically close to the borrowing firms and that have lending expertise related to the industries of the borrowers. We also examine factors that influence the relation between ownership structure and syndicate structure, including lead arranger reputation, prior lending relationship, borrowing firm informational opacity, presence of multiple large owners, laws and institutions, and financial crises.postprin

Ownership structure and the cost of corporate borrowing

This article identifies an important channel through which excess control rights affect firm value. Using a new, hand-collected data set on corporate ownership and control of 3,468 firms in 22 countries during the 1996–2008 period, we find that the cost of debt financing is significantly higher for companies with a wider divergence between the largest ultimate owner’s control rights and cash-flow rights and investigate factors that affect this relation. Our results suggest that potential tunneling and other moral hazard activities by large shareholders are facilitated by their excess control rights. These activities increase the monitoring costs and the credit risk faced by banks and, in turn, raise the cost of debt for the borrower.postprin

Corporate ownership structure and the choice between bank debt and public debt

This article examines the relation between a borrowing firm's ownership structure and its choice of debt source using a novel data set on corporate ownership, control, and debt structures for 9,831 firms in 20 countries from 2001 to 2010. We find that the divergence between the control rights and cash-flow rights of a borrowing firm's largest ultimate owner has a significant negative impact on the firm's reliance on bank debt financing. In addition, we show that the control-ownership divergence affects other aspects of debt structure including debt maturity and security. Our results indicate that firms controlled by large shareholders with excess control rights may choose public debt financing over bank debt as a way of avoiding scrutiny and insulating themselves from bank monitoring.postprin

EARLY MUSIC NEL NOVECENTO ITALIANO

My Ph.D. dissertation focuses on the Early Music movement in Italy between the second post-war period and the end of the seventies in a historic-cultural point of view, limited to the revival of the Medieval repertoire. It is an initial inquiry of a complex and international phenomenon, whose Italian manifestation has still not been an object of research. In this work the phenomenon Early Music \u2013 analysed through historical, historiographic and ethnographic criteria \u2013 is settled into the broader Italian political, social and cultural context in order to underline the peculiarities, to detect the ideological, esthetical and political reasons which nourished it and to set up connections with other Italian experiences in the second half of the 20th Century, not only what music concern. The work is articulated in two sections. The first part focuses on the early music activity from the period of the post-war reconstruction to the early sixties, through the revival of the lauda and of the liturgical drama repertoire, particularly rich in those years. The first chapter deals with the presence of Medieval music in the cultural life of the post-war period, both what discography and live performance concern, with a particular attention on the attitude of the musical criticism. The second chapter broadens the chronologic span researching the origins of the lauda\u2019s fortune during the Fascist era, aiming to a better comprehension of the phenomenon in the following decades. The third chapter focuses on Milan and on the activity of the choral ensemble Polifonica Ambrosiana in order to underline the revival of the ancient Italian repertoire and the choral practise as moment not only of musical, but also of moral reconstruction for the catholic communities before and during the Vatican Council. The second part examines the decade following the sixty-eight. The first chapter inserts the Italian experience into the international Early Music movement\u2019s frame in the period of the socio-political revolutions, so as to highlight the consonances between the performance and use of early music and the sixty-eight ideals. The second chapter underlines the role of the pre-baroque music as a stimulus to the creation of an alternative musical education towards the academic one, while the third offers a bird\u2019s eye view on the activity of the Italian groups specialised in Medieval music, pointing out some fundamental elements for the construction their identity and self-legitimation. The fourth chapter delves into the Italian Communist Party\u2019s position about cultural politics and its activity within the recreational clubs. The objects of the last chapter are the musical, ideological and political synergies with experiences such as folk-revival and, more generally, with the performance of the folk repertoire and oral tradition

Modes of extensional faulting controlled by surface processes

We investigate the feedbacks between surface processes and tectonics in an extensional setting by coupling a 2-D geodynamical model with a landscape evolution law. Focusing on the evolution of a single normal fault, we show that surface processes significantly enhance the amount of horizontal extension a fault can accommodate before being abandoned in favor of a new fault. In simulations with very slow erosion rates, a 15 km thick brittle layer extends via a succession of crosscutting short-lived faults (heave 10 km). Using simple scaling arguments, we quantify the effect of surface mass removal on the force balance acting on a growing normal fault. This leads us to propose that the major range-bounding normal faults observed in many continental rifts owe their large offsets to erosional and depositional processes

Autogenic entrenchment patterns and terraces due to coupling with lateral erosion in incising alluvial channels

The abandonment of terraces in incising alluvial rivers can be used to infer tectonic and climatic histories. A river incising into alluvium erodes both vertically and laterally as it abandons fill-cut terraces. We argue that the input of sediment from the valley walls during entrenchment can alter the incision dynamics of a stream by promoting vertical incision over lateral erosion. Using a numerical model, we investigate how valley wall feedbacks may affect incision rates and terrace abandonment as the channel becomes progressively more entrenched in its valley. We postulate that erosion of taller valley walls delivers large pulses of sediment to the incising channel, potentially overwhelming the local sediment transport capacity. Based on field observations, we propose that these pulses of sediment can form talus piles that shield the valley wall from subsequent erosion and potentially force progressive channel narrowing. Our model shows that this positive feedback mechanism can enhance vertical incision relative to 1-D predictions that ignore lateral erosion. We find that incision is most significantly enhanced when sediment transport rates are low relative to the typical volume of material collapsed from the valley walls. The model also shows a systematic erosion of the youngest terraces when river incision slows down. The autogenic entrenchment due to lateral feedbacks with valley walls should be taken into account in the interpretation of complex-response terraces

Spin and Charge Luttinger-Liquid Parameters of the One-Dimensional Electron Gas

Low-energy properties of the homogeneous electron gas in one dimension are completely described by the group velocities of its charge (plasmon) and spin collective excitations. Because of the long range of the electron-electron interaction, the plasmon velocity is dominated by an electrostatic contribution and can be estimated accurately. In this Letter we report on Quantum Monte Carlo simulations which demonstrate that the spin velocity is substantially decreased by interactions in semiconductor quantum wire realizations of the one-dimensional electron liquid.Comment: 13 pages, figures include

Histochemical and morpho-metrical study of mouse intestine epithelium after a long term diet containing genetically modified soybean

Diet can influence the structural characteristics of both small and large intestine. In this study, we investigated the duodenum and colon of mice fed on genetically modified (GM) soybean during their whole life span (1–24 months) by focusing our attention on the histological and ultrastructural characteristics of the epithelium, the histochemical pattern of goblet cell mucins, and the growth profile of the coliform population. Our results demonstrate that controls and GM-soybean fed mice are similarly affected by ageing. Moreover, the GM soybean-containing diet does not induce structural alterations in duodenal and colonic epithelium or in coliform population, even after a long term intake. On the other hand, the histochemical approach revealed significant diet-related changes in mucin amounts in the duodenum. In particular, the percentage of villous area occupied by acidic and sulpho-mucin granules decreased from controls to GM-fed animals, whereas neutral mucins did not change