Dynamical paths and universality in continuous variables open systems

We address the dynamics of quantum correlations in continuous variable open systems and analyze the evolution of bipartite Gaussian states in independent noisy channels. In particular, upon introducing the notion of dynamical path through a suitable parametrization for symmetric states, we focus attention on phenomena that are common to Markovian and non-Markovian Gaussian maps under the assumptions of weak coupling and secular approximation. We found that the dynamical paths in the parameter space are universal, that is they do depend only on the initial state and on the effective temperature of the environment, with non Markovianity that manifests itself in the velocity of running over a given path. This phenomenon allows one to map non-Markovian processes onto Markovian ones and it may reduce the number of parameters needed to study a dynamical process, e.g. it may be exploited to build constants of motions valid for both Markovian and non-Markovian maps. Universality is also observed in the value of Gaussian discord at the separability threshold, which itself is a function of the sole initial conditions in the limit of high temperature. We also prove the existence of excluded regions in the parameter space, i.e. of sets of states which cannot be linked by any Gaussian dynamical map.Comment: 7 pages, 2 figures, improved pictures and forma

SPACE AND OSTEOPOROSIS: HOW GRAVITY AFFECTS BONE MICROENVIRONMENT

The aim of this study is to get insights into space-associated osteoporosis and cardiovascular deconditioning, which are important adverse effects of spaceflight. These disorders are strikingly similar to common diseases caused by sedentary life, senescence and degenerative diseases on Earth. Therefore, investigating the alterations occurring in microgravity will significantly improve our knowledge about the mechanisms leading to disease, thus fostering the development of novel approaches and countermeasures to improve the quality of life of millions of people on Earth and of a few hundreds in space. Studies at the cellular and molecular level are necessary to understand the mechanisms underlying osteoporosis and cardiovascular deconditioning. Two main questions were asked: 1. how microgravity affects cultured human endothelial cells and 2. how microgravity impacts on bone cells. Different microgravity simulators were used for cell culture experiments. Evidence has been provided about the marked sensitivity of endothelial cells to real and simulated microgravity. On the basis of previous experiments in space and on Earth, Human Umbilical Vein Endothelial Cells (HUVEC), widely used as a model of macrovascular endothelial cells, were studied and shown to dynamically adapt to simulated microgravity. Indeed, HUVEC rapidly upregulate heat shock protein (HSP)70 and this increase is maintained up to day 4 from exposure to microgravity. At later time points, HSP70 returns to basal level, while an overexpression of paraoxonase (PON)2, sirtuin (SIRT)2, HSP27 and P-HSP27 is detected. This late adaptive response counterbalances the increase of Thioredoxin-Interacting Protein (TXNIP) and prevents the accumulation of reactive oxygen species. Thanks to this adaptive response, no dysfunction occurs in HUVEC in simulated microgravity. This is an important finding, since endothelial cells are responsible for the integrity of the vascular wall. Because of the heterogeneity of the endothelium, some experiments were also performed on human microvascular endothelial cells (HMEC). Like HUVEC, HMEC rapidly upregulate HSP70, indicating the activation of an adaptive response, and do not undergo apoptosis. Differently from HUVEC, HMEC are growth retarded in microgravity. Accordingly, p21 increases in a p53 independent fashion. Moreover, they secrete higher amounts of tissue inhibitor of matrix metalloprotease (TIMP)-2 and interleukin (IL)-6 than controls in 1G-conditions. The data obtained in HMEC were a pre-requisite for the following experiments. Since signals from endothelial cells condition the behavior of osteoblasts and are fundamental for healthy bone, I utilized media collected form HMEC exposed to simulated microgravity to culture human osteoblasts. My studies demonstrate that conditioned media collected from microvascular endothelial cells exposed to microgravity inhibit osteoblast function by impairing alkaline phosphatase activity and calcium deposition in the extracellular matrix. This inhibitory effect might be due to the increased secretion by HMEC of IL-6 and TIMP-2. On these bases, it is feasible to propose that microgravity impairs osteoblast activity both directly -as demonstrated in real and simulated microgravity- and indirectly by altering endothelial/osteoblast communication. Some studies have shown not only an impairment of osteoblast but also an increase of osteoclast activity in real and simulated microgravity. However, very little is known about the effect of microgravity on the osteogenic potential of human mesenchymal stem cells (MSC). To this purpose, MSC were cultured in simulated microgravity in the presence or in the absence of an osteogenic cocktail. No alterations in osteogenic differentiation of MSC occur in simulated microgravity as demonstrated by the modulation of osteogenic markers and by the deposition of calcium, suggesting that these cells are not involved in space-associated osteoporosis. It is noteworthy that, like endothelial cells, MSC upregulate stress proteins, some of which are implicated in osteogenesis. It is clear that endothelial cells and MSC sense microgravity as a stressor, and consequently activate a stress response that not only maintains the cells viable but also allows them to reach a novel homeostatic state so that they can perform, at least in part, their activity

Burning magnesium, a sparkle in acute inflammation: gleams from experimental models

Magnesium contributes to the regulation of inflammatory responses. Here, we focus on the role of magnesium in acute inflammation. Although present knowledge is incomplete to delineate an accurate scenario and a schedule of the events occurring under magnesium deficiency, it emerges that low magnesium status favors the induction of acute inflammation by sensitizing sentinel cells to the noxious agent, and then by participating to the orchestration of the vascular and cellular events that characterize the process

Role of traditional and new biomarkers in breast carcinogenesis

In recent decades, several biomarkers have been investigated as predictors of breast cancer risk, development, prognosis and treatment efficacy

Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera. These results were phenocopied in endothelial cells cultured in a medium containing high concentrations of glucose, which activates inducible nitric oxide synthase with a consequent increase of nitric oxide. Inhibition of the enzyme prevented high glucose-induced hyperpermeability, thus pointing to nitric oxide as the mediator involved in altering the endothelial barrier function. Since nitric oxide is much higher in sera from hyperglycaemic than normoglycaemic T1D patients, and the inhibition of inducible nitric oxide synthase prevents sera-dependent increased endothelial permeability, this enzyme might represent a promising biochemical marker to be monitored in T1D patients to predict alterations of the vascular wall, eventually promoting intimal lipid accumulation

Mitophagy contributes to endothelial adaptation to simulated microgravity

Exposure to real or simulated microgravity is sensed as a stress by mammalian cells, which activate a complex adaptive response. In human primary endothelial cells, we have recently shown the sequential intervention of various stress proteins which are crucial to prevent apoptosis and maintain cell function. We here demonstrate that mitophagy contributes to endothelial adaptation to gravitational unloading. After 4 and 10 d of exposure to simulated microgravity in the rotating wall vessel, the amount of BCL2 interacting protein 3, a marker of mitophagy, is increased and, in parallel, mitochondrial content, oxygen consumption, and maximal respiratory capacity are reduced, suggesting the acquisition of a thrifty phenotype to meet the novel metabolic challenges generated by gravitational unloading. Moreover, we suggest that microgravity induced-disorganization of the actin cytoskeleton triggers mitophagy, thus creating a connection between cytoskeletal dynamics and mitochondrial content upon gravitational unloading

Genomic imbalances are confined to non-proliferating cells in paediatric patients with acute myeloid leukaemia and a normal or incomplete karyotype

Copyright @ 2011 Ballabio et al.Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.This work was supported by a grant from Leukaemia Research UK (grant no. 0253). SJLK and RR were supported by the NIHR Biomedical Research Centre, Oxford, with funding from the Department of Health’s NIHR Biomedical Research Centres funding schemeThis article is available through the Brunel Open Access Publishing Fund

Smart technologies for effective reconfiguration: the FASTER approach

Current and future computing systems increasingly require that their functionality stays flexible after the system is operational, in order to cope with changing user requirements and improvements in system features, i.e. changing protocols and data-coding standards, evolving demands for support of different user applications, and newly emerging applications in communication, computing and consumer electronics. Therefore, extending the functionality and the lifetime of products requires the addition of new functionality to track and satisfy the customers needs and market and technology trends. Many contemporary products along with the software part incorporate hardware accelerators for reasons of performance and power efficiency. While adaptivity of software is straightforward, adaptation of the hardware to changing requirements constitutes a challenging problem requiring delicate solutions. The FASTER (Facilitating Analysis and Synthesis Technologies for Effective Reconfiguration) project aims at introducing a complete methodology to allow designers to easily implement a system specification on a platform which includes a general purpose processor combined with multiple accelerators running on an FPGA, taking as input a high-level description and fully exploiting, both at design time and at run time, the capabilities of partial dynamic reconfiguration. The goal is that for selected application domains, the FASTER toolchain will be able to reduce the design and verification time of complex reconfigurable systems providing additional novel verification features that are not available in existing tool flows

Metabolic gatekeeper function of B-lymphoid transcription factors.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation

Anharmonic calculations of vibrational spectra for molecular adsorbates: A divide-and-conquer semiclassical molecular dynamics approach

The vibrational spectroscopy of adsorbates is becoming an important investigation tool for catalysis and material science. This paper presents a semiclassical molecular dynamics method able to reproduce the vibrational energy levels of systems composed by molecules adsorbed on solid surfaces. Specifically, we extend our divide-and-conquer semiclassical method for power spectra calculations to gas-surface systems and interface it with plane-wave electronic structure codes. The Born-Oppenheimer classical dynamics underlying the semiclassical calculation is full dimensional, and our method includes not only the motion of the adsorbate but also those of the surface and the bulk. The vibrational spectroscopic peaks related to the adsorbate are accounted together with the most coupled phonon modes to obtain spectra amenable to physical interpretations. We apply the method to the adsorption of CO, NO, and H2O on the anatase-TiO2 (101) surface. We compare our semiclassical results with the single-point harmonic estimates and the classical power spectra obtained from the same trajectory employed in the semiclassical calculation. We find that CO and NO anharmonic effects of fundamental vibrations are similarly reproduced by the classical and semiclassical dynamics and that H2O adsorption is fully and properly described in its overtone and combination band relevant components only by the semiclassical approach