Olfactory receptors for a smell sensor: A comparative study of the electrical responses of rat I7 and human 17-40

In this paper we explore relevant electrical properties of two olfactory receptors (ORs), one from rat OR I7 and the other from human OR 17-40, which are of interest for the realization of smell nanobiosensors. The investigation compares existing experiments, coming from electrochemical impedance spectroscopy, with the theoretical expectations obtained from an impedance network protein analogue, recently developed. The changes in the response due to the sensing action of the proteins are correlated with the conformational change undergone by the single protein. The satisfactory agreement between theory and experiments points to a promising development of a new class of nanobiosensors based on the electrical properties of sensing proteins.Comment: 6 pages, 7 figure

A Biased Resistor Network Model for Electromigration Failure and Related Phenomena in Metallic Lines

Electromigration phenomena in metallic lines are studied by using a biased resistor network model. The void formation induced by the electron wind is simulated by a stochastic process of resistor breaking, while the growth of mechanical stress inside the line is described by an antagonist process of recovery of the broken resistors. The model accounts for the existence of temperature gradients due to current crowding and Joule heating. Alloying effects are also accounted for. Monte Carlo simulations allow the study within a unified theoretical framework of a variety of relevant features related to the electromigration. The predictions of the model are in excellent agreement with the experiments and in particular with the degradation towards electrical breakdown of stressed Al-Cu thin metallic lines. Detailed investigations refer to the damage pattern, the distribution of the times to failure (TTFs), the generalized Black's law, the time evolution of the resistance, including the early-stage change due to alloying effects and the electromigration saturation appearing at low current densities or for short line lengths. The dependence of the TTFs on the length and width of the metallic line is also well reproduced. Finally, the model successfully describes the resistance noise properties under steady state conditions.Comment: 39 pages + 17 figure

Tuning the Correlation Decay in the Resistance Fluctuations of Multi-Species Networks

A new network model is proposed to describe the $1/f^\alpha$ resistance noise in disordered materials for a wide range of $\alpha$ values ($0< \alpha < 2$). More precisely, we have considered the resistance fluctuations of a thin resistor with granular structure in different stationary states: from nearly equilibrium up to far from equilibrium conditions. This system has been modelled as a network made by different species of resistors, distinguished by their resistances, temperature coefficients and by the energies associated with thermally activated processes of breaking and recovery. The correlation behavior of the resistance fluctuations is analyzed as a function of the temperature and applied current, in both the frequency and time domains. For the noise frequency exponent, the model provides $0< \alpha < 1$ at low currents, in the Ohmic regime, with $\alpha$ decreasing inversely with the temperature, and $1< \alpha <2$ at high currents, in the non-Ohmic regime. Since the threshold current associated with the onset of nonlinearity also depends on the temperature, the proposed model qualitatively accounts for the complicate behavior of $\alpha$ versus temperature and current observed in many experiments. Correspondingly, in the time domain, the auto-correlation function of the resistance fluctuations displays a variety of behaviors which are tuned by the external conditions.Comment: 26 pages, 16 figures, Submitted to JSTAT - Special issue SigmaPhi200

GM-CSF AND MMP9 ARE KEY REGULATORS OF THE EFFECT OF ADIPOSE PROGENITORS OVER BREAST CANCER ONSET AND METASTATIC PROGRESSION

Recent epidemiological and clinical data underlined the critical role of obesity in breast cancer (BC) progression. Among several white adipose tissue (WAT) cells, which may promote a permissive tumor microenvironment, a population with progenitor-like phenotype (CD45-CD34+) was reported to support local and metastatic BC. This population is composed by distinct WAT progenitors: adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs), displaying complementary role in BC progression in preclinical models. However, molecular mechanisms involved in this interaction have been so far elusive and need to be clarified. An extensive screening of candidate molecules revealed two proteins being significantly up-regulated in WAT-derived progenitors after being co-cultured with several BC cells: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Matrix metallopeptidase 9 (MMP9). Both factors were detected over-expressed in orthotopic xenograft models, when co-injected with BC and human WAT progenitors. ASC and EPCs displayed similar ability to induce GM-CSF/MMP9, suggesting a complementary role in their release. GM-CSF neutralization in WAT progenitors inhibited MMP9 secretion, which was also reduced by IL-1\u3b2 neutralization. GM-CSF displayed an additional positive feedback regulation on its own release. The inhibition of GM-CSF in diet-induced obese (DIO) syngeneic mice led to reduced intratumor vascularization and strong impairment of immunosuppressive microenvironment, targeting mainly tumor-associated macrophages (TAMs), myeloid derived suppressor cells (MDSCs) and T-regulatory (T-regs) cells. This resulted in a significant impairment of local BC growth and a slower metastatic progression. Conversely, MMP9 inhibition reduced neoplastic angiogenesis and significantly decreased local and metastatic tumor growth. The combined GM-CSF/MMP9 inhibition synergically impaired tumor angiogenesis, local and metastatic BC growth. Metformin was reported to significantly affect tumor progression and neoplastic angiogenesis, targeting both BC and WAT cells. In the present study, Metformin inhibited GM-CSF and MMP9 release from WAT progenitors in vitro and in xenograft models. Metformin had similar effects of GM-CSF/MMP9 specific inhibitions in DIO syngeneic mice, but was more effective in reducing tumor angiogenesis and targeted different immune cells. Collectively, these results indicate GM-CSF and MMP9 as new potential targets to prevent the pro-tumorigenic effect of WAT progenitors on BC. Furthermore, Metformin ability to reduce GM-CSF and MMP9 supports Metformin administration in clinical studies on BC, especially in a setting of obesity and/or insulin resistance

TCAD Modeling of High-Field Electron Transport in Bulk Wurtzite GaN: The Full-Band SHE-BTE

Gallium Nitride (GaN) High-Electron Mobility Transistors (HEMTs) actually represent one of the best candidates for medium-high power and radio frequency applications. As they operate at large bias and electric fields, a comprehensive analysis of the high-field transport properties is fundamentals, as hot electrons are expected to play a relevant role for the device reliability. In this perspective, Technology Computer-Aided Design (TCAD) simulations can be a very useful tool for the understanding of the phenomena dominating hot-electron degradation mechanisms. The most-accurate modeling approaches are based on the direct solution of the Boltzmann equation, which is not actually available for the GaN material. In this work, the deterministic solution of the Boltzmann transport equation via the spherical-harmonics expansion (SHE-BTE), as incorporated in a commercial TCAD tool, has been extended to the analysis of GaN electrons. To this purpose, the details of the full-band structure has been derived from DFT calculations as in state-of-art literature works, and the electron density of states, g(E), and group velocity g(E), have been calculated for the SHE-BTE for the first time. In addition to this, an accurate calibration of the total scattering rate accounting for nonpolar acoustic and optical carrier-phonon interaction, Coulomb scattering and impact ionization has been carried out against available Monte Carlo data and experiments. The proposed model is also shown to correctly predict the temperature dependence of the electron impact-ionization coefficient and current density up to breakdown

Childhood and assistance: a work in progress European project

The Institute for History Researches in Vicenza has widened its field of work which, until that moment, it was \u201cthe other\u201d Europe. The institute is undertaking a research project on abandoned childhood between East and West\u201d. This project, which involves, until now, Italy, Ukraine and Romania, was born from the idea that social services for underage in the past had important similarities: from these observations is possible to deduce that the phenomenon was not only a peculiarity of the Western word, but it was spread all over Europe. The hypothesis of work is to put in comparison the different realities, realizing a useful operation for the general historical comprehension. Nowadays, the possibility of a comparison among different areas represents indeed the opportunity to rebuild the long-term circulation of ideas existing in the first years of the 20th century, as it is demonstrated by the multiplying of the international congresses on charity and childhood from the last years of the 19th century. Having a look to the past, the comparison enables to understand how these similarities have been growing slowly, through which channels and exchanges, how much they were truthful and how much they were simulated and how much, indeed, after the October revolution, the two parties of Europe were keeping similar customs. In this perspective, the project aims to open a construction site of research to go in depth with the comparison, giving relevance, in this phase, after some initial considerations, to a couple of specific and at the same time wide themes. The first one is the exchange of concepts and practices from one point of Europe to the other. The paths of these exchanges have to be traced period by period, identifying different levels: the one carried over by books, by treatises, by mails etc, and the one carried over by people \u2013kings, high prelates, intellectuals, officials, travellers and so on- as well. The second theme analysed in the research, suggested by several studies conducted on social services realities in Italy, is born observing that institutes for underage were at the centre of a complex net of social, economic and political relationships with the territory. The reconstruction of this net and its evolution over the centuries enables to better understand the origin of the great variety of solutions adopted at the local level. Different and variable were the beneficiaries, different and variable were the welcoming habits and the organization of the social services, as well as there were different and variable perspectives of social re-integration, which had to conform, for example, to the productive transformations and the government projects. The idea supporting the research is to build a geographic history that helps to understand if and how the \u201cmodels\u201d preferred from time to time were consistent with the economic and social context in which the institutes were re-integrating their attendees, after having welcomed them. The scientific committee of the project is, at present time, composed by: Francesca Lomastro, from the Institute for history researches of Vicenza, Italy; Ioan Aurel Pop, from Cluj-Napoca University, Romania; Flores Reggiani, from the University of the Studies of Milan, Italy; Yuriy Shapoval, from the Sciences Academia of Kiev, Ukraine

Poorly differentiated clusters (PDC) in colorectal cancer: what is and ought to be known.

The counting of poorly differentiated clusters of 5 or more cancer cells lacking a gland-like structure in a tumor mass has recently been identified among the histological features predictive of poor prognosis in colorectal cancer. Poorly differentiated clusters can easily be recognized in the histological sections of colorectal cancer routinely stained with haematoxylin and eosin. Despite some limitations related to specimen fragmentation, counting can also be assessed in endoscopic biopsies. Based on the number of poorly differentiated clusters that appear under a microscopic field of a ×20 objective lens (i.e., a microscopic field with a major axis of 1 mm), colorectal cancer can be graded into malignancies as follows: tumors with &lt;5 clusters as grade 1, tumors with 5 to 9 clusters as grade 2, and tumors with ≥10 clusters as grade 3. High poorly differentiated cluster counts are significantly associated with peri-neural and lympho-vascular invasion, the presence of nodal metastases or micrometastases, as well as shorter overall and progression free survival to colorectal cancer. The morphological aspects and clinical relevance of poorly differentiated clusters counting in colorectal cancer are discussed in this review