Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

Photoconductivity and photoluminescence under bias in GaInNAs/GaAs MQW p-i-n structures

The low temperature photoluminescence under bias (PLb) and the photoconductivity (PC) of a p-i-n GaInNAs/GaAs multiple quantum well sample have been investigated. Under optical excitation with photons of energy greater than the GaAs bandgap, PC and PLb results show a number of step-like increases when the sample is reverse biased. The nature of these steps, which depends upon the temperature, exciting wavelength and intensity and the number of quantum wells (QWs) in the device, is explained in terms of thermionic emission and negative charge accumulation due to the low confinement of holes in GaInNAs QWs. At high temperature, thermal escape from the wells becomes much more dominant and the steps smear out.     

Electrode surface treatments in sludge electro-osmosis dewatering

The sewage sludge dewatering produced by wastewater treatment plants (WWTP) is a multifaceted process due to the presence of colloid fractions. Electro-osmosis could be a suitable technique to reduce the water content of the final sludge. Electric fields of 10, 15, and 20?V/cm have been studied for electro-osmosis tests under the pressure of a static or rotating piston, obtaining a dry solids content up to 40–45%, with respect to 25–30% obtained by mechanical methods. In order to optimize the process, the corrosion behavior and the wear of the anodic material appear to be the main critical aspects, due to the high circulating current density and the use of a rotating electrode. We compared the efficiency and the corrosion resistance of dimensionally stable anodes (DSA) with respect to bare stainless steel (AISI 304) and stainless steel coated by PVD technique with TiN, AlTiN, and DLC. Characterization of the anode surfaces by SEM and potentiodynamic tests show that DSA is the most suitable material for our application. However, efficiencies of the electro-osmosis processes have been found comparable, in terms of developed current densities and total energy consumptions, for short-test duration.     

Mapping average equivalized income using robust small area methods

Measures of economic well‐being are often needed for geographically small areas, as economic indicators may be distributed unevenly among the subsets of relatively small regions. We consider small area estimation of average equivalized income. Disposable household income data are usually available only for a sample of households, typically too small to provide reliable estimates for small regions. We consider a small area estimation technique that is robust to outliers, produces results consistent with design weighted estimates obtained for larger areas and yield maps with approximately no shrinkage. The proposed methodology is applied to the Local Labour Systems in Tuscany (Italy).     

Proteomics in the Diagnosis of Endometriosis: Opportunities and Challenges

The non‐surgical diagnosis of endometriosis is still challenging for the clinician. Ultrasonography and magnetic resonance imaging can be used to diagnose ovarian endometriotic cysts and deep infiltrating endometriosis; but their performance is poor in the diagnosis of initial stages of endometriosis. CA‐125 and other serum markers (such as CA 19‐9, serum protein PP14, interleukins, and angiogenetic factors) have been measured in women with endometriosis but they are not reliable for the diagnosis of the disease. Although several studies used proteomics technologies to identify plasmatic markers of endometriosis, the non‐invasive diagnosis of endometriosis is far from being achieved. In this issue, Manousopoulou et al. compare the integrated quantitative proteomic profile of eutopic endometrium and serum of women with endometriosis and controls. 1214 proteins are differentially expressed in the eutopic endometrium and 404 proteins in the serum of the two study groups. 21 proteins are aberrantly expressed in both eutopic endometrium and serum of women with endometriosis. More work is needed to assess if the differentially expressed proteins identified in this study can be used as clinical markers of endometriosis.     

Thermodiffusion‐Assisted Pyroelectrics—Enabling Rapid and Stable Heat and Radiation Sensing

Sensors for monitoring temperature, heat flux, and thermal radiation are essential for applications such as electronic skin. While pyroelectric and thermoelectric effects are suitable candidates as functional elements in such devices, both concepts show individual drawbacks in terms of zero equilibrium signals for pyroelectric materials and small or slow response of thermoelectric materials. Here, these drawbacks are overcome by introducing the concept of thermodiffusion‐assisted pyroelectrics, which combines and enhances the performance of pyroelectric and ionic thermoelectric materials. The presented integrated concept provides both rapid initial response upon heating and stable synergistically enhanced signals upon prolonged exposure to heat stimuli. Likewise, incorporation of plasmonic metasurfaces enables the concept to provide both rapid and stable signals for radiation‐induced heating. The performance of the concept and its working mechanism can be explained by ion–electron interactions at the interface between the pyroelectric and ionic thermoelectric materials.     

Auto-Regressive Moving Average Models on Complex-Valued Matrix Lie Groups

The present contribution aims at extending the classical scalar autoregressive moving average (ARMA) model to generate random (as well as deterministic) paths on complex-valued matrix Lie groups. The numerical properties of the developed ARMA model are studied by recurring to a tailored version of the Z-transform on Lie groups and to statistical indicators tailored to Lie groups, such as correlation functions on tangent bundles. The numerical behavior of the devised ARMA model is also illustrated by numerical simulations.     

Influence of free carbon on the Young's modulus and hardness of polymer-derived silicon oxycarbide glasses

Silicon oxycarbide (SiOC) glasses in the form of thin, dense, and crack-free samples were fabricated according to the polymer pyrolysis route starting from cross-linked polysiloxane. The amount of free carbon in the final SiOC materials was varied in the range 18-60 vol%. The mechanical properties of the SiOC glasses were measured by nanoindentaion technique and revealed that both the Young's modulus and the hardness decrease with increase in the free carbon content and follow a simple rule of mixtures model.     

Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase

The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided.     

Ice‐Templated Scaffolds with Microridged Pores Direct DRG Neurite Growth

Successful spinal cord repair is thought to be promoted with hierarchically structured scaffolds. These should combine aligned porosity with additional linear features on the micrometer scale to guide axons across multiple length scales. Such scaffolds are generated through the carefully controlled directional solidification of an aqueous biopolymer solution, followed by lyophilization. Under specific freezing conditions this yields a highly regular and aligned lamellar architecture. This architecture exhibits uniform ridges of controlled height and width on the lamellar surface. These ridges run parallel to the pore axis, serving as secondary guidance features. The ridges are capable of linearly aligning 62.4% of chick dorsal root ganglia neurites to within ±10° of the ridge direction. Notably, neurites sprouting perpendicular to the ridge are guided into alignment with these microridged features.