3d modeling of tumor growth

This paper briefly describes a numerical model of avascular solid tumors that has recently been developed in Trieste and Verona. The model includes a mathematical description of the cell metabolism and of the cell cycle and includes the cells’ biomechanics. The model has been successfully validated with experimental data. The resulting software may be to used to perform in-silico tests, and can be further upgraded in a modular way

Analysis of the fluctuations of the tumour/host interface

In a recent analysis of metabolic scaling in solid tumours we found a scaling law that interpolates between the power laws μ∝V and μ∝V2∕3, where μ is the metabolic rate expressed as the glucose absorption rate and V is the tumour volume. The scaling law fits quite well both in vitro and in vivo data, however we also observed marked fluctuations that are associated with the specific biological properties of individual tumours. Here we analyse these fluctuations, in an attempt to find the population-wide distribution of an important parameter (A) which expresses the total extent of the interface between the solid tumour and the non-cancerous environment. Heuristic considerations suggest that the values of the A parameter follow a lognormal distribution, and, allowing for the large uncertainties of the experimental data, our statistical analysis confirms this

Pulsation-limited oxygen diffusion in the tumour microenvironment

Hypoxia is central to tumour evolution, growth, invasion and metastasis. Mathematical models of hypoxia based on reaction-diffusion equations provide seemingly incomplete descriptions as they fail to predict the measured oxygen concentrations in the tumour microenvironment. In an attempt to explain the discrepancies, we consider both the inhomogeneous distribution of oxygen-consuming cells in solid tumours and the dynamics of blood flow in the tumour microcirculation. We find that the low-frequency oscillations play an important role in the establishment of tumour hypoxia. The oscillations interact with consumption to inhibit oxygen diffusion in the microenvironment. This suggests that alpha-blockers\u2013a class of drugs used to treat hypertension and stress disorders, and known to lower or even abolish low-frequency oscillations of arterial blood flow \u2013may act as adjuvant drugs in the radiotherapy of solid tumours by enhancing the oxygen effect

Using graph theory for automated electric circuit solving

Graph theory plays many important roles in modern physics and in many different contexts, spanning diverse topics such as the description of scale-free networks and the structure of the universe as a complex directed graph in causal set theory. Graph theory is also ideally suited to describe many concepts in computer science. Therefore it is increasingly important for physics students to master the basic concepts of graph theory. Here we describe a student project where we develop a computational approach to electric circuit solving which is based on graph theoretic concepts. This highly multidisciplinary approach combines abstract mathematics, linear algebra, the physics of circuits, and computer programming to reach the ambitious goal of implementing automated circuit solving

Analysis of Novel Mycobacteriophages Indicates the Existence of Different Strategies for Phage Inheritance in Mycobacteria

Mycobacteriophages have been essential in the development of mycobacterial genetics through their use in the construction of tools for genetic manipulation. Due to the simplicity of their isolation and variety of exploitable molecular features, we searched for and isolated 18 novel mycobacteriophages from environmental samples collected from several geographic locations. Characterization of these phages did not differ from most of the previously described ones in the predominant physical features (virion size in the 100?400 nm, genome size in the 50?70 kbp, morphological features compatible with those corresponding to the Siphoviridae family), however novel characteristics for propagation were noticed. Although all the mycobacteriophages propagated at 30uC, eight of them failed to propagate at 37uC. Since some of our phages yielded pinpoint plaques, we improved plaque detection by including sub-inhibitory concentrations of isoniazid or ampicillin-sulbactam in the culture medium. Thus, searches for novel mycobacteriophages at low temperature and in the presence of these drugs would allow for the isolation of novel members that would otherwise not be detected. Importantly, while eight phages lysogenized Mycobacterium smegmatis, four of them were also capable of lysogenizing Mycobacterium tuberculosis. Analysis of the complete genome sequence obtained for twelve mycobacteriophages (the remaining six rendered partial genomic sequences) allowed for the identification of a new singleton. Surprisingly, sequence analysis revealed the presence of parA or parA/parB genes in 7/18 phages including four that behaved as temperate in M. tuberculosis. In summary, we report here the isolation and preliminary characterization of mycobacteriophages that bring new information to the field.Fil: Stella, Emma Julieta. Universidad Nacional de Rosario. Facultad de Cs.medicas. Escuela de Cs.medicas. Cat.de Microbiologia,parasitologia y Virologia;Fil: Franceschelli, Jorgelina Judith. Universidad Nacional de Rosario. Facultad de Cs.medicas. Escuela de Cs.medicas. Cat.de Microbiologia,parasitologia y Virologia;Fil: Tasselli, Sabrina Emilse. Universidad Nacional de Rosario. Facultad de Cs.medicas. Escuela de Cs.medicas. Cat.de Microbiologia,parasitologia y Virologia;Fil: Morbidoni, Héctor Ricardo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Escuela de Cs.medicas. Cat.de Microbiologia,parasitologia y Virologia

Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein

It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regulate tumour cell sensitivity to radiation. We develop a new statistical and experimental approach to quantify the effects of radiation on cell populations as a whole. In our experiments, we change the proximity relationships of the cells by culturing them in wells with different shapes, and we find that the radiosensitivity of T47D human breast carcinoma cells in tight clusters is different from that of isolated cells. Molecular analyses show that T47D cells express a Syncytin-1 homologous protein (SyHP). We observe that SyHP translocates to the external surface of the plasma membrane of cells killed by radiation treatment. The data support the fundamental role of SyHP in the formation of intercellular cytoplasmic bridges and in the enhanced radioresistance of surviving cells. We conclude that complex and unexpected biological mechanisms of tumour radioresistance take place at the cell population level. These mechanisms may significantly bias our estimates of the radiosensitivity of breast carcinomas in vivo and thereby affect treatment plans, and they call for further investigations

Use of GPUs to boost the performance of a lattice-free tumour growth model

We recently developed a computational model of tumour growth. It is a cell- based model that can simulate the growth of multicellular tumour spheroids up to more than one million cells. The simulation program is very demanding and simulation time severely limits the integration of additional biological details, and indeed, at the moment, a typical simulation run requires tens of days to be completed. A new version of the code that exploits Graphics Processing Units (GPUs) to boost performance is being developed. In this paper we describe the design and implementation of a nearest-neighbour search (NNS) algorithm suitable to run on GPU. The algorithm will be integrated in the original code to manage the geometrical calculation in the simulation of the spheroid. Initially the stand alone NNS algorithm was tested for spheroids of different size: better efficency was obtained for bigger spheroids. Eventually the code was integrated in the whole simulation code and preliminary runs gave a speed up of about 5 for spheroids of relatively small size (15000 cells)

Interplay between early-life malnutrition, epigenetic modulation of the immune function and liver diseases

Early-life nutrition plays a critical role in fetal growth and development. Food intake absence and excess are the two main types of energy malnutrition that predispose to the appearance of diseases in adulthood, according to the hypothesis of 'developmental origins of health and disease'. Epidemiological data have shown an association between early-life malnutrition and the metabolic syndrome in later life. Evidence has also demonstrated that nutrition during this period of life can affect the development of the immune system through epigenetic mechanisms. Thus, epigenetics has an essential role in the complex interplay between environmental factors and genetics. Altogether, this leads to the inflammatory response that is commonly seen in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. In conjunction, DNA methylation, covalent modification of histones and the expression of non-coding RNA are the epigenetic phenomena that affect inflammatory processes in the context of NAFLD. Here, we highlight current understanding of the mechanisms underlying developmental programming of NAFLD linked to epigenetic modulation of the immune system and environmental factors, such as malnutrition.Fil: Campisano, Sabrina Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: Echarte, Stella Maris. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Chisari, Andrea Nancy. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentin

Clinical, Microbiological, and Genetic Characteristics of Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Bacteremia in a Teaching Hospital

The emergence of vancomycin intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) is of major concern worldwide. Our objective was to investigate the prevalence, phenotypic and molecular features of hVISA strains isolated from bacteremic patients and to determine the clinical significance of the hVISA phenotype in patients with bacteremia. A total of 104 S. aureus blood isolates were collected from a teaching hospital of Argentina between August 2009 and November 2010. No VISA isolate was recovered, and 3 out of 92 patients (3.3%) were infected with hVISA, 2 of them methicillin-resistant S. aureus (MRSA) (4.5% of MRSA). Macro Etest and prediffusion method detected 3/3 and 2/3 hVISA respectively. Considering the type of bacteremia, the three cases were distributed as follows: two patients had suffered multiple episodes of bacteremia (both hVISA strains recovered in the second episode), while only one patient had suffered a single episode of bacteremia with hVISA infection. MRSA bloodstream isolates exhibiting the hVISA phenotype were related to HA-MRSA Cordobes clone (ST5-SCCmec I-spa t149) and MRSA Argentinean pediatric clone (ST100-SCCmec IVNV-spa t002), but not to CA-MRSA-ST30-SCCmec IV-spa t019 clone that was one of the most frequent in our country. Although still relatively infrequent in our hospital, hVISA strains weresignificantly associated with multiple episodes of bacteremia ( p = 0.037) and genetically unrelated.Fil: Di Gregorio, Sabrina Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Perazzi, Beatriz Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Martinez Ordoñez, Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: de Gregorio, Stella. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Focoli, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Lasala, María Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Garcia, Susana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Vay, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Famiglietti, Angela María Rosa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin