Modulation on C‐ and N‐Terminal Moieties of a Series of Potent and Selective Linear Tachykinin NK2 Receptor Antagonists

Herein we describe the synthesis of a series of new potent tachykinin NK₂ receptor antagonists by the modulation of the C‐ and N‐terminal moieties of ibodutant (MEN 15596, 1 ). The N‐terminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C‐terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK₂ receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK₂ receptor. Selected compounds were tested in vivo confirming their activity as NK₂ antagonists. In particular, after both iv and id administration to guinea pig, compound 61 b was able to antagonize NK₂‐induced colonic contractions with a potency and duration‐of‐action fully comparable to the reference compound 1 (MEN 15596, ibodutant).     

A backoff strategy for model‐based experiment design under parametric uncertainty

Model‐based experiment design techniques are an effective tool for the rapid development and assessment of dynamic deterministic models, yielding the most informative process data to be used for the estimation of the process model parameters. A particular advantage of the model‐based approach is that it permits the definition of a set of constraints on the experiment design variables and on the predicted responses. However, uncertainty in the model parameters can lead the constrained design procedure to predict experiments that turn out to be, in practice, suboptimal, thus decreasing the effectiveness of the experiment design session. Additionally, in the presence of parametric mismatch, the feasibility constraints may well turn out to be violated when that optimally designed experiment is performed, leading in the best case to less informative data sets or, in the worst case, to an infeasible or unsafe experiment. In this article, a general methodology is proposed to formulate and solve the experiment design problem by explicitly taking into account the presence of parametric uncertainty, so as to ensure both feasibility and optimality of the planned experiment. A prediction of the system responses for the given parameter distribution is used to evaluate and update suitable backoffs from the nominal constraints, which are used in the design session to keep the system within a feasible region with specified probability. This approach is particularly useful when designing optimal experiments starting from limited preliminary knowledge of the parameter set, with great improvement in terms of design efficiency and flexibility of the overall iterative model development scheme. The effectiveness of the proposed methodology is demonstrated and discussed by simulation through two illustrative case studies concerning the parameter identification of physiological models related to diabetes and cancer care. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

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.     

High-precision isothermal titration calorimetry with automated peak-shape analysis

Isothermal titration calorimetry (ITC) is a powerful classical method that enables researchers in many fields to study the thermodynamics of molecular interactions. Primary ITC data comprise the temporal evolution of differential power reporting the heat of reaction during a series of injections of aliquots of a reactant into a sample cell. By integration of each injection peak, an isotherm can be constructed of total changes in enthalpy as a function of changes in solution composition, which is rich in thermodynamic information on the reaction. However, the signals from the injection peaks are superimposed by the stochastically varying time-course of the instrumental baseline power, limiting the precision of ITC isotherms. Here, we describe a method for automated peak assignment based on peak-shape analysis via singular value decomposition in combination with detailed least-squares modeling of local pre- and postinjection baselines. This approach can effectively filter out contributions of short-term noise and adventitious events in the power trace. This method also provides, for the first time, statistical error estimates for the individual isotherm data points. In turn, this results in improved detection limits for high-affinity or low-enthalpy binding reactions and significantly higher precision of the derived thermodynamic parameters.     

Progress in control and data acquisition for the ITER neutral beam test facility

SPIDER, the ion source test bed in the ITER neutral beam test facility, is under construction and its operation is expected to start in 2014. Control and data acquisition for SPIDER are undergoing final design. SPIDER CODAS, as the control and data acquisition system is referred to, is requested to manage 25 plant units, to acquire 1000 analogue signals with sampling rates ranging from a few S/s to 10 MS/s, to acquire images with up to 100 frames per second, to operate with long pulses lasting up to 1 h, and to sustain 200 MB/s data throughput into the data archive with an annual data storage amount of up to 50 TB. SPIDER CODAS software architecture integrates three open-source software frameworks each addressing specific system requirements. Slow control exploits the synergy among EPICS and Siemens S7 programmable controllers. Data handling is by MDSplus a data-centric framework that is geared towards the collection and organization of scientific data. Diagnostics based on imaging drive the design of data throughput and archive size. Fast control is implemented by using MARTe, a data-driven, object-oriented, real-time environment. The paper will describe in detail the progress of the system hardware and software architecture and will show how the software frameworks interact to provide the functions requested by SPIDER CODAS. The paper will focus on how the performance requirements can be met with the described SPIDER CODAS architecture, describing the progress achieved by carrying out prototyping activities.     

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.     

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.     

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.