The microbiota impact. bacteria shaping immunity, disease and response to therapy

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Not only P-glycoprotein: amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins

The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies. Upon repeated or even single dose treatment of cultured tumor cells or tumors in vivo with anti-tumor agents such as paclitaxel and doxorubicin, increased ABCB1 copy number has been demonstrated, resulting from chromosomal amplification events at 7q11.2-21 locus, leading to marked P-glycoprotein overexpression, and multidrug resistance (MDR). Clearly however, additional mechanisms such as single nucleotide polymorphisms (SNPs) and epigenetic modifications have shown a role in the overexpression of ABCB1 and of other MDR efflux pumps. However, notwithstanding the design of 4 generations of ABCB1 inhibitors and the wealth of information on the biochemistry and substrate specificity of ABC transporters, translation of this vast knowledge from the bench to the bedside has proven to be unexpectedly difficult. Many studies show that upon repeated treatment schedules of cell cultures or tumors with taxenes and anthracyclines as well as other chemotherapeutic drugs, amplification, and/or overexpression of a series of genes genomically surrounding the ABCB1 locus, is observed. Consequently, altered levels of other proteins may contribute to the establishment of the MDR phenotype, and lead to poor clinical outcome. Thus, the genes contained in this ABCB1 amplicon including ABCB4, SRI, DBF4, TMEM243, and RUNDC3B are overexpressed in many cancers, and especially in MDR tumors, while TP53TG1 and DMTF1 are bona fide tumor suppressors. This review describes the role of these genes in cancer and especially in the acquisition of MDR, elucidates possible connections in transcriptional regulation (co-amplification/repression) of genes belonging to the same ABCB1 amplicon region, and delineates their novel emerging contributions to tumor biology and possible strategies to overcome cancer MDR

Monitoring dispersive samples with single photons: the role of frequency correlations

The physics that governs quantum monitoring may involve other degrees of freedom than the ones initialised and controlled for probing. In this context we address the simultaneous estimation of phase and dephasing characterizing a dispersive medium, and we explore the role of frequency correlations within a photon pair generated via parametric down-conversion, when used as a probe for the medium. We derive the ultimate quantum limits on the estimation of the two parameters, by calculating the corresponding quantum Cram\'er-Rao bound; we then consider a feasible estimation scheme, based on the measurement of Stokes operators, and address its absolute performances in terms of the correlation parameters, and, more fundamentally, of the role played by correlations in the simultaneous achievability of the quantum Cram\'er-Rao bounds for each of the two parameters.Comment: to appear in Quantum Measurements and Quantum Metrolog

Confronto di solutori FEM e solutori BEM per lo sloshing in contenitori

Ė stato studiato il fenomeno di sloshing attraverso due diversi algoritmi numerici: il primo consiste in una discretizzazione con elementi finiti dell’equazione di Navier Stokes in formulazione Arbitrary Lagrangian Eulerian, è indicato nel seguito come FEM ed è descritto in [3]; il secondo è basato sulla discretizzazione delle equazioni agli integrali di contorno e delle equazioni di evoluzione della superficie libera ed è indicato come BEM e descritto in [2]. Per verificare la validità dei due codici sono stati confrontati i loro risultati con quelli presenti in letteratura, sia derivanti da altri codici numerici, sia ottenuti come risultati sperimentali. Il confronto è stato effettuato per un’ampia gamma di situazioni, in modo da studiare il comportamento dei due codici al variare delle caratteristiche della sollecitazione e delle dimensioni del dominio

Noisy quantum walks of two indistinguishable interacting particles

We investigate the dynamics of continuous-time two-particle quantum walks on a one-dimensional noisy lattice. Depending on the initial condition, we show how the interplay between particle indistinguishability and interaction determines distinct propagation regimes. A realistic model for the environment is considered by introducing non-Gaussian noise as time-dependent fluctuations of the tunneling amplitudes between adjacent sites. We observe that the combined effect of particle interaction and fast noise (weak coupling with the environment) provides a faster propagation compared to the noiseless case. This effect can be understood in terms of the band structure of the Hubbard model, and a detailed analysis as a function of both noise and system parameters is presented.Comment: 9 pages, 8 figure

Multiparameter quantum estimation of noisy phase shifts

Phase estimation is the most investigated protocol in quantum metrology, but its performance is affected by the presence of noise, also in the form of imperfect state preparation. Here we discuss how to address this scenario by using a multiparameter approach, in which noise is associated to a parameter to be measured at the same time as the phase. We present an experiment using two-photon states, and apply our setup to investigating optical activity of fructose solutions. Finally, we illustrate the scaling laws of the attainable precisions with the number of photons in the probe state

Neuropragmatics: Extralinguistic communication after closed head injury

This work is concerned with the decay of communicative abilities after head trauma. A protocol composed of 16 videotaped scenes was devised in order to investigate the comprehension of several types of communicative actions realized with extralinguistic means, like pointing or clapping. The protocol was administered to 30 closed head injured individuals. The results showed a decreasing performance from simple standard acts, to complex standard acts, deceits, and ironies. The subjects' performance was worse with the scenes reproducing failing, rather than successful, communicative actions. The results are compared with those we previously obtained with a linguistic protocol. A theory of the cognitive processes underlying intentional communication is outlined and used to explain the results