Aging and Immortality in a Cell Proliferation Model

We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.Comment: 6 pages, 1 figure, 2-column revtex4 format; version 2: final published form; contains various improvements in response to referee comment

Costruire in pietra, pratica e storia. Laboratorio di stereotomia - Palermo 2016

Il volume raccoglie i contributi presentati in occasione del seminario introduttivo al Laboratorio di stereotomia, tenutosi presso il Dipartimento di Architettura dell'Università degli studi di Palermo nel mese di aprile del 2016, e un contributo che illustra quest'ultima esperienza. Nel complesso, i diversi saggi ruotano intorno al tema della costruzione in pietra nell'ambito dell'architettura tardogotica, con particolare attenzione alle volte, osservata da diversi punti di vista e ambiti disciplinari che spaziano dalla storia, al disegno, alla storia della costruzione. Ricerca e didattica si intrecciano e concorrono a fare nuova luce su esperienze costruttive di primo piano nella storia dell'architettura europea, secondo una modalità già sperimentata da José Carlos Palacios Gonzalo nel Laboratorio di costruzione gotica dell'Universidad Politecnica di Madrid e replicata a Palermo nel Laboratorio di stereotomiaThis volume collects the contributions presented at the introductory seminar at Laboratory of stereotomy, held at the Department of Architecture of the University of Palermo in April of 2016, and a contribution that illustrates this last experience. All the essays deal with the theme of the stone building in late Gothic architecture, with particular attention to the vaults, observed from different points of view and disciplines ranging from history, to drawing, to construction history . Research and teaching are intertwined and help to shed new light on experiences prominent in the history of European architecture, according to a methodology already tested by José Carlos Gonzalo Palacios in the Gothic building Laboratory of the Universidad Politecnica de Madrid and replicated in Palermo in the Laboratory of stereotomy

3D INTEGRATED SURVEYS AND STRATIGRAPHIC METHODS FOR A DEEPER UNDERSTANDING OF HISTORICAL BUILDINGS. A CASE-STUDY OF THE FRANCISCAN MONASTERY AND THE IMMACOLATA CHURCH IN TROINA, SICILY

Abstract. The study presents the results of the application of a multidisciplinary methodology for a deeper understanding of historical buildings. 3D integrated surveys and stratigraphic methods can together make it possible to date the principle construction and evolution phases of historical buildings for which a thorough historical documentation does not exist for our time.The case-study presented involves the Franciscan monastery and adjacent Immacolata church in Troina, which is a small medieval town located in the north-eastern part of Sicily.The small number of historical records has only allowed for the dating of the monastery's foundation and of a few of transformation phases. Contrarily to this, various markings on the surfaces of the walls indicate rather the presence of numerous construction phases.The inaccessibility of parts of the internal spaces, as well as the existence of a sharp incline of the road and of very high walls along scant sections of the road, are the reasons for having chosen to carry out a 3D laser-scanning survey campaign. It made it possible to document the overall area and the relationship between the different parts of the complex. The integration between 3D laser scanning and photo-modelling methods made it possible to highlight the details, anomalies, traces and signs of the stratifications over time. The results of this integrated survey were explained in a series of graphic elaborations in support to the following stratigraphic investigation, to put in order the numerous traces discovered.</p

Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity.

The accumulation of senescent cells (SnCs) is a causal factor of various age-related diseases as well as some of the side effects of chemotherapy. Pharmacological elimination of SnCs (senolysis) has the potential to be developed into novel therapeutic strategies to treat these diseases and pathological conditions. Here we show that ubiquitin-specific peptidase 7 (USP7) is a novel target for senolysis because inhibition of USP7 with an inhibitor or genetic depletion of USP7 by RNA interference induces apoptosis selectively in SnCs. The senolytic activity of USP7 inhibitors is likely attributable in part to the promotion of the human homolog of mouse double minute 2 (MDM2) ubiquitination and degradation by the ubiquitin-proteasome system. This degradation increases the levels of p53, which in turn induces the pro-apoptotic proteins PUMA, NOXA, and FAS and inhibits the interaction of BCL-XL and BAK to selectively induce apoptosis in SnCs. Further, we show that treatment with a USP7 inhibitor can effectively eliminate SnCs and suppress the senescence-associated secretory phenotype (SASP) induced by doxorubicin in mice. These findings suggest that small molecule USP7 inhibitors are novel senolytics that can be exploited to reduce chemotherapy-induced toxicities and treat age-related diseases

The role of inflammation in age-related disease.

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation inAge-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified

Quantum Jarzynski Equality with multiple measurement and feedback for isolated system

In this paper, we derive the Jarzynski equality (JE) for an isolated quantum system in three different cases: (i) the full evolution is unitary with no intermediate measurements, (ii) with intermediate measurements of arbitrary observables being performed, and (iii) with intermediate measurements whose outcomes are used to modify the external protocol (feedback). We assume that the measurements will involve errors that are purely classical in nature. Our treatment is based on path probability in state space for each realization. This is in contrast to the formal approach based on projection operator and density matrices. We find that the JE remains unaffected in the second case, but gets modified in the third case where the mutual information between the measured values with the actual eigenvalues must be incorporated into the relation.Comment: 7 page

GROWTH AND YIELDS OF 'ARBEQUINA' HIGH-DENSITY PLANTING SYSTEMS IN THREE DIFFERENT OLIVE GROWING AREAS IN ITALY

The sustainability of the traditional olive-growing sector in EU countries characterised by high production costs and a low selling price for the oil was mainly determined by EU subsidies available for the sector. With the opening of the free trade area by the Barcellona Declaration of 1995 and a cut in EU subsidies in 2014, crucial changes in the sector are now needed. In order to increase the competitiveness of EU olive production, attention should be given to new high-yielding and mechanized cultivation systems. In the 1990s, Spain introduced new high-density planting systems (1,200-2,000 trees/ha) using three low-vigour and early-fruiting cultivars ( Arbequina , Arbosana and Koroneiki ). Italian olive production lies in a geographical area that stretches for about 6\ub0 in latitude (37-43\ub0 latitude N) and in the band of altitude which ranges from sea level to 400 m a.s.l. Studies on the ecophysiology of woody plants show the importance of adapting the planting system to the climate of the cultivation site, particularly for high-density groves. The evaluation of cultivars suitable for high-density systems, based on their vegetative characteristics, branching and fruiting, together with an analysis of product quality, may contribute significantly to the development and diffusion of new crop growing systems. To achieve this aim, joint research was carried out by three different research units operating in the three main olive-growing regions of Italy (Sicily, Apulia and Umbria). This paper illustrates the first results (2010 and 2011) obtained by the PRIN Project on Biological processes and environmental factors affecting the vegetative growth, fruiting and oil quality control in a high density olive (Olea europaea L.) planting system

Thermodynamics and Fluctuation Theorems for a Strongly Coupled Open Quantum System: An Exactly Solvable Case

We illustrate recent results concerning the validity of the work fluctuation theorem in open quantum systems [M. Campisi, P. Talkner, and P. H\"{a}nggi, Phys. Rev. Lett. {\bf 102}, 210401 (2009)], by applying them to a solvable model of an open quantum system. The central role played by the thermodynamic partition function of the open quantum system, -- a two level fluctuator with a strong quantum nondemolition coupling to a harmonic oscillator --, is elucidated. The corresponding quantum Hamiltonian of mean force is evaluated explicitly. We study the thermodynamic entropy and the corresponding specific heat of this open system as a function of temperature and coupling strength and show that both may assume negative values at nonzero low temperatures.Comment: 8 pages, 6 figure

INTRA-CULTIVAR DIVERSITY IN SOUTHERN ITALY OLIVE CULTIVARS DEPICTED BY MORPHOLOGICAL TRAITS AND SSR MARKERS

In this study, SSR analysis was performed on a large number of putative clones of the main olive cultivars from two Italian regions, Sicily and Calabria, in order to study the genetic relatedness, and to detect any degree of genetic diversity, which can be used to unambiguously identify possible superior clones. These putative clones have been collected and observed in the last ten years, following an extensive investigation carried out in traditional olive growing areas, thanks to the reports of farmers, millers, technician, growers and nurseries. The set of microsatellite (SSR) markers used allowed the detection of the genetic diversity, resulting from somatic mutation, indicating the presence of polyclonal cultivars, or having gametic origin, indicating a seedling origin of many clones, which thus share sibling relationships. The presence of superior clones or superior genotypes is discussed

Quantum Jarzynski-Sagawa-Ueda relations

We consider a (small) quantum mechanical system which is operated by an external agent, who changes the Hamiltonian of the system according to a fixed scenario. In particular we assume that the agent (who may be called a demon) performs measurement followed by feedback, i.e., it makes a measurement of the system and changes the protocol according to the outcome. We extend to this setting the generalized Jarzynski relations, recently derived by Sagawa and Ueda for classical systems with feedback. One of the two relations by Sagawa and Ueda is derived here in error-free quantum processes, while the other is derived only when the measurement process involves classical errors. The first relation leads to a second law which takes into account the efficiency of the feedback.Comment: 11 pages. a major revision in v.2. Minor revision in v.3. The present version will appear in J. Stat. Phy