Recent technological advancements in radiofrequency- andmicrowave-mediated hyperthermia for enhancing drug delivery

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes

Development and evaluation of a methodology to integrate technical and sensorial properties in materials selection.

In the materials selection process, the use of different tools, languages and perspectives frequently causes disagreement between engineers and industrial designers. The aim of the paper is to define an integrated method for materials selection that provides industrial designers with measurable data to support and explain aesthetic decisions on materials. A new method for materials selection consisting of multiple tools structured in a two-step framework is presented. The method is tested through a case study of professional kitchen appliances where metal components are replaced with polymers. The first step involved the application of an established technique to identify polymeric bulk solutions, based on their technical properties. The second step employed a sensory analysis test to choose suitable finishes. Thirty-seven individuals performed the test: the subjects highlighted their main perceptions of metal and metal-look polymer finishes. The research demonstrates that the proposed method is suitable for the evaluation of both technical and sensorial properties of materials. In particular, Mapping test represents a rapid, low cost and effective tool to help industrial designers justify Colour Materials and Finish (CMF) choices with quantifiable information

Distinct phosphorylation clusters determines the signalling outcome of the free fatty acid receptor FFA4/GPR120

It is established that long-chain free fatty acids including ω-3 fatty acids mediate an array of biological responses through members of the free fatty acid receptor family, which includes FFA4. However, the signalling mechanisms and modes of regulation of this receptor class remain unclear. Here we employ mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C terminal tail, designated cluster 1 (Thr347, Thr349 and Ser350) and cluster 2 (Ser357 and Ser361). Mutation of these phospho-acceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to ERK1/2 activation. Rather an inhibitor of Gq/11 proteins completely prevented receptor signalling to ERK1/2. In contrast, the recruitment of arrestin 3, receptor internalization and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signalling was extended further by selective mutations of the phospho-acceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phospho-acceptor sites within cluster 1 had no effect on receptor internalization and a less extensive effect on arrestin 3 recruitment, but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signalling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signalling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C-terminus of the receptor

Model-based prediction of maximum pool size in the ribbon synapse

The synaptic ribbon is a specialized structure in photoreceptor neurons that tethers vesicles prior to release (Figure 1A). When a cell is stimulated, vesicles are released from the ribbon and later replenished from the population of mobile vesicles in the synaptic terminal. A train of depolarizing pulses causes the ribbon to alternate between periods of release (lasting Δt = 25 ms) and replenishment (lasting T = 50ms), which occur on estimated timescales of τr = 5 ms (for release) and τa = 815ms (for replenishment). After the first few pulses, the system approaches a limit cycle, and the amount of vesicles released on each pulse converges to a limiting value, R (Figure 1B). This can be used to determine the maximum available pool size on the ribbon, A. The standard method for estimating A is to measure the rate of replenishment in the limit, and then back-extrapolate from the cumulative release plot to obtain the available pool size at the start of the pulse train [1]. When comparing pulse trains of different strengths, this method yields substantially different values for A, a somewhat paradoxical result. Back-extrapolation assumes, however, that the replenishment rate is constant, even though it is thought to be proportional to the available space on the ribbon [2]

Utilizzo di nitrati come inibitori di corrosione per le armature nel calcestruzzo

Corrosion inhibitors have been long considered as an effective preventative technique to slow down the onset and/or propagation of corrosion phenomena in reinforced concrete. Several substances have been evaluated as possible candidates, and great interest has been dedicated to nitrite ion. When investigating how these substances slow down corrosion related processes – chlorides diffusion, critical chloride threshold, CO2 penetration and corrosion propagation –interactions between inhibitor and concrete are also vital. Recently, nitrate based compounds have been proposed as corrosion inhibitors, as they present lower cost than nitrites and are already used in concrete as set accelerators. Some studies have shown that nitrates inhibiting mechanism is similar to that of nitrites. This work proposes the evaluation of a nitrate based substance as possible corrosion inhibitor in concrete, and compares its performance with a nitrite based inhibitor

The Spitzer search for the transits of HARPS low-mass planets - II. Null results for 19 planets

Short-period super-Earths and Neptunes are now known to be very frequent around solar-type stars. Improving our understanding of these mysterious planets requires the detection of a significant sample of objects suitable for detailed characterization. Searching for the transits of the low-mass planets detected by Doppler surveys is a straightforward way to achieve this goal. Indeed, Doppler surveys target the most nearby main-sequence stars, they regularly detect close-in low-mass planets with significant transit probability, and their radial velocity data constrain strongly the ephemeris of possible transits. In this context, we initiated in 2010 an ambitious Spitzer multi-Cycle transit search project that targeted 25 low-mass planets detected by radial velocity, focusing mainly on the shortest-period planets detected by the HARPS spectrograph. We report here null results for 19 targets of the project. For 16 planets out of 19, a transiting configuration is strongly disfavored or firmly rejected by our data for most planetary compositions. We derive a posterior probability of 83% that none of the probed 19 planets transits (for a prior probability of 22%), which still leaves a significant probability of 17% that at least one of them does transit. Globally, our Spitzer project revealed or confirmed transits for three of its 25 targeted planets, and discarded or disfavored the transiting nature of 20 of them. Our light curves demonstrate for Warm Spitzer excellent photometric precisions: for 14 targets out of 19, we were able to reach standard deviations that were better than 50ppm per 30 min intervals. Combined with its Earth-trailing orbit, which makes it capable of pointing any star in the sky and to monitor it continuously for days, this work confirms Spitzer as an optimal instrument to detect sub-mmag-deep transits on the bright nearby stars targeted by Doppler surveys.Comment: Accepted for publication in Astronomy and Astrophysics. 23 pages, 21 figure

Unusual clear cell variant of epithelioid mesothelioma

Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed

Constraints on fNL from Wilkinson Microwave Anisotropy Probe 7-year data using a neural network classifier

We present a multi-class neural network (NN) classifier as a method to measure nonGaussianity, characterised by the local non-linear coupling parameter fNL, in maps of the cosmic microwave background (CMB) radiation. The classifier is trained on simulated non-Gaussian CMB maps with a range of known fNL values by providing it with wavelet coefficients of the maps; we consider both the HealPix (HW) wavelet and the spherical Mexican hat wavelet (SMHW). When applied to simulated test maps, the NN classfier produces results in very good agreement with those obtained using standard chi2 minimization. The standard deviations of the fNL estimates for WMAPlike simulations were {\sigma} = 22 and {\sigma} = 33 for the SMHW and the HW, respectively, which are extremely close to those obtained using classical statistical methods in Curto et al. and Casaponsa et al. Moreover, the NN classifier does not require the inversion of a large covariance matrix, thus avoiding any need to regularise the matrix when it is not directly invertible, and is considerably faster.Comment: Accepted for publication in MNRAS, 9 pages, 5 figures, 1 tabl

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors.

At the first synapse in the vertebrate visual pathway, light-evoked changes in photoreceptor membrane potential alter the rate of glutamate release onto second-order retinal neurons. This process depends on the synaptic ribbon, a specialized structure found at various sensory synapses, to provide a supply of primed vesicles for release. Calcium (Ca(2+)) accelerates the replenishment of vesicles at cone ribbon synapses, but the mechanisms underlying this acceleration and its functional implications for vision are unknown. We studied vesicle replenishment using paired whole-cell recordings of cones and postsynaptic neurons in tiger salamander retinas and found that it involves two kinetic mechanisms, the faster of which was diminished by calmodulin (CaM) inhibitors. We developed an analytical model that can be applied to both conventional and ribbon synapses and showed that vesicle resupply is limited by a simple time constant, τ = 1/(Dρδs), where D is the vesicle diffusion coefficient, δ is the vesicle diameter, ρ is the vesicle density, and s is the probability of vesicle attachment. The combination of electrophysiological measurements, modeling, and total internal reflection fluorescence microscopy of single synaptic vesicles suggested that CaM speeds replenishment by enhancing vesicle attachment to the ribbon. Using electroretinogram and whole-cell recordings of light responses, we found that enhanced replenishment improves the ability of cone synapses to signal darkness after brief flashes of light and enhances the amplitude of responses to higher-frequency stimuli. By accelerating the resupply of vesicles to the ribbon, CaM extends the temporal range of synaptic transmission, allowing cones to transmit higher-frequency visual information to downstream neurons. Thus, the ability of the visual system to encode time-varying stimuli is shaped by the dynamics of vesicle replenishment at photoreceptor synaptic ribbons