Insulin Resistance and Cancer: In Search for a Causal Link

Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development.     

Removal of fulvic acid from aqueous media by adsorption onto modified vermiculite

Clay minerals are low cost materials that can be structurally modified and exploited for removal of natural organic matter from freshwaters. The present study shows that vermiculites modified by ion exchange with hexadecyltrimethylammonium or intercalation with poly(hydroxy iron) cations are potential adsorbents for removal of fulvic acid, whereas the adsorption on the raw clay mineral is negligible. The efficiency of the modified vermiculite was evaluated by measuring adsorption isotherms by the batch technique using initial fulvic acid concentrations between 2.5 and 50.0 mg L^− 1, with one hour of contact time. At least 94% of the fulvic acid initially present in a 20 mg L^− 1 solution was sorbed onto either the intercalated poly(hydroxy iron) cations or the organically modified vermiculite. Up to an initial concentration of 5.0 mg L^− 1 the adsorption is irreversible, and no quantifiable fulvic acid was measured in the desorption experiments. For initial fulvic acid concentrations between 10.0 and 50.0 mg L^− 1, desorption was between 2.3% and 4.9% for Fe(III) intercalated vermiculite, and between 1.4% and 9.2% for the organoclay. The adsorption percentages on intercalated poly(hydroxy iron) cations increased upon lowering pH and increasing the ionic strength, indicating the occurrence of strong binding mechanisms such as ligand exchange. Adsorption percentage of fulvic acid onto the organoclay also increased with lowering of pH, but in this case the adsorption percentages showed a small decrease at high ionic strength, suggesting that electrostatic attraction plays an important role in the adsorption process.     

Industry–research co‐operation within and across regional boundaries. What does innovation policy add?

The paper aims to show how regional policy‐makers can stimulate firms' co‐operation with research organizations by granting an R&D subsidy. Using an original dataset for the Italian region of Emilia‐Romagna, propensity score matching is first applied to identify the impact of the subsidy received. A generalized propensity score technique is then employed to investigate the effect of an increasing amount of support. The firm's co‐operation is policy sensitive. The award of a subsidy to regional firms affects their intra‐regional more than their extra‐regional co‐operation. The propensity toward the latter appears subject to a monetary effect and is influenced by the amount of public funding received providing the subsidy overcomes a minimum threshold.     

Consequence-based management of railroad bridge networks

To increase profitability, add capacity and comply with new federal regulations on bridge safety, North American railroads are exploring means to improve the management of their bridge networks. Current maintenance, repair and replacement (MRR) decisions are informed by bridge inspections and ratings, which recommend observing the response of bridges under trains. However, an objective relationship between bridge responses and the associated impact to railroad operations has yet to be established. If the consequences of MRR decisions could be better determined, then the railroads could more effectively allocate their limited resources. Chief bridge engineers from different Class I railroads provided the values of displacements and assessment used to develop this paper. Researchers monitored displacements from over 50 train crossing events and related them to decisions on operations and maintenance. This paper develops an approach for consequence-based management of bridge networks for making network MRR decisions, employing fragility curves to relate service condition limit states to transverse displacement. The operational costs associated with these service conditions can estimate the total costs of a given MRR policy. In this way, optimum MRR decisions can minimise the total network costs. This framework provides a consistent approach for the prioritisation of railroad bridge MRR decisions.     

Investigation of cure kinetics in epoxy/multiwalled carbon nanotube nanocomposites

With the increased interest in thermoset resin nanocomposites, it is important to understand the effects of the material on nanoscale characteristics. In this study, a curing reaction of an epoxy resin, which contained 0.25, 0.50, or 1.00 wt % of multiwalled carbon nanotubes (MWCNTs), at different heating rates was monitored by differential scanning calorimetry; cure kinetics were also evaluated to establish a relationship between crosslinking (network formation) and mechanical properties. MWCNT concentrations above 0.25 wt % favored crosslinking formation and decreased the activation energy (E_a) in the curing reaction. Examination of the kinetic mechanism suggests that the MWCNT locally restricted the spatial volume and favored the formation of nodular morphology in the resin, especially for high MWCNT concentrations. The MWCNT exhibited some entanglement in the matrix, which hindered a more pronounced effect on the mechanical properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39857.     

Small‐Molecule Inhibitors of AF6 PDZ‐Mediated Protein–Protein Interactions

PDZ (PSD‐95, Dlg, ZO‐1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ‐mediated protein–protein interactions has important implications in disease‐related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1‐fused gene from chromosome 6), which is an essential component of cell–cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile‐Gln‐Ser‐Val‐Glu‐Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6–Bcr interaction and interfere with epidermal growth factor (EGF)‐dependent signaling.     

A new sawing machine by diamond wire

Diamond wire is widely used for stone cutting; it is typically employed to extract a block in quarry and to square the block in a machining company. In particular, the frames to square or to cut the blocks present many technological limits, such as the high costs of the diamond wire, the frequent break of the diamond wire during cutting, the poor quality of cut surfaces, and the dangerous process and productivity lower than that of the same tool used in a quarry. The present work shows an innovative prototype machine to cut by a diamond wire which overcomes the aforementioned technological limits. The developed machine has a bridge frame among which two pulleys move the diamond wire as regards the stone block according with the feed speed. The diamond wire moves on the two pulleys with a cutting speed. A tensile force is applied to the wire that twists it during the contact with the stone, instead of keeping it along a straight direction parallel to the foundation of the machine. The twisting of the diamond wire makes the use of the wire itself more productive and safer, since the wear of each single bead during cutting is more uniform. Moreover, the resulting specific pressure acts on each bead along the arc of contact with the cut block and increases along the cutting direction from the entrance to the exit of the contact with the stone. The increasing of the specific pressure causes a bending of the diamond wire during the contact with the stone. The developed prototype was provided with a sensory system to measure both the cutting power and the tensile force of the diamond wire during experimental tests. In this way it was possible to verify the functionality of the prototype plant and, in the same time, to evaluate the productivity of the implemented cutting process.     

Metabolites from the biodegradation of di-ester plasticizers by Rhodococcus rhodochrous

The plasticizers di-2-ethylhexyl phthalate (DEHP) and di-2-ethylhexyl adipate (DEHA) are ubiquitous in the environment and undergo partial biodegradation in the presence of soil micro-organisms. The validity of a proposed pathway for the degradation of these plasticizers by Rhodococcus rhodochrous has been confirmed by the identification of 2-ethylhexanal in gas phase emissions. Complete analyses of the aqueous and gas phases were able to account for more than 98% of the 2-ethylhexanol component of the DEHA added at the beginning of a growth study. Of this, 25% was either 2-ethylhexanol or 2-ethylhexanal that had been stripped into the gas phase and, at most, only 2% of the 2-ethylhexanol component could have been removed by mineralization. It is concluded that plasticizers are of significant environmental concern due to the resistance of the metabolites to biodegradation and their known health impacts. Two of the metabolites are of added concern due to their volatility and their potential impact on indoor air quality.