Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor

The urokinase receptor (uPAR) is a cell‐surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here, we evaluate the binding and biological activity of a new class of pyrrolidinone and piperidinone compounds, along with derivatives of previously‐identified pyrazole and propylamine compounds. Competition assays revealed that the compounds displace a fluorescently labeled peptide (AE147‐FAM) with inhibition constant (K_i) values ranging from 6 to 63 μM . Structure‐based computational pharmacophore analysis followed by extensive explicit‐solvent molecular dynamics (MD) simulations and free energy calculations suggested the pyrazole‐based and piperidinone‐based compounds adopt different binding modes, despite their similar two‐dimensional structures. In cells, pyrazole‐based compounds showed significant inhibition of breast adenocarcinoma (MDA‐MB‐231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but piperidinone‐containing compounds exhibited no cytotoxicity even at concentrations of 100 μM . One pyrazole‐based compound impaired MDA‐MB‐231 invasion, adhesion, and migration in a concentration‐dependent manner, while the piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix metalloprotease‐9 (gelatinase) activity in a concentration‐dependent manner, while the piperidinone showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF‐κB signaling, while pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that the effect of the pyrazole‐based compound on proliferation was due to cell killing through an apoptotic mechanism. The compounds identified represent valuable leads in the design of further derivatives with higher affinities and potential probes to unravel the protein–protein interactions of uPAR.     

Connectivity analysis for dynamic movement of vehicular ad hoc networks

Speed variation is one of the main challenges in deriving the connectivity related predictions in mobile ad-hoc networks, especially in vehicular ad hoc networks (VANETs). In such a dynamic network, a piece of information can be rapidly propagated through dedicated short-range communication, or can be carried by vehicles when multihop connectivity is unavailable. This paper proposes a novel analytical model that carefully computes the connectivity distance for a single direction of a free-flow highway. The proposed model adopts a time-varying vehicular speed assumption and mathematically models the mobility of vehicles inside connectivity. According to the dynamic movability scenario, a novel and accurate closed form formula is proposed for probability density function of connectivity. Moreover, using vehicular spatial distribution, joint Poisson distribution of vehicles in a multilane highway and tail probability of the expected number of vehicles inside single lane in a multilane highway are mathematically investigated. The accuracy of analytical results is verified by simulation. The concluded results provide helpful insights towards designing new applications and improving performance of existing applications on VANETs.     

Photostability study of natural high-potency sweetener monatin in a model beverage system and characterisation of the degradation products

Photodegradation of the naturally occurring high-potency sweetener monatin was studied in a lemon-lime beverage model system under simulated conditions. Most of the monatin disappeared after treatment with the equivalent of four days of ultraviolet light exposure and resulted in the formation of a number of degradation products. These degradation products have been isolated and characterised in the present study. On the basis of these identified structures, a photodegradation pathway has been proposed suggesting that monatin gets oxidised on the indole C-2 position to result in 2-hydroxymonatin. It also undergoes decarboxylation resulting in a 4-oxopentanoic acid analog and a major rearrangement resulting in an isonicotinic acid analog. Monatin also degrades into 3-formylindole and indole-3-carboxylic acid. Besides these, a partial monatin dimer and a monatin lactone were identified as additional degradation products. Details of the isolation and characterisation are given.     

Experimental and numerical analysis of aerodynamic effects of repair patches on damaged airfoils

This investigation assesses the change of aerodynamic characteristics of triangular and star-shaped damaged airfoils with repair patches. Both experimental and numerical methods to determine aerodynamic coefficients are used in this study. The test model is a NACA 64₁-412 airfoil full span, which is considered by using five schematics: Clean model, damaged model, upper repaired model, lower repaired model, and fully repaired model. Repair patches are chosen based on the Aircraft battle damage repair (ABDR) manuals. Various effects of repair schemes on triangular and star-shaped damages are quantitatively and qualitatively illustrated. A novel visualization method by paint and oil is used in wind tunnel tests to study the effects of repair patches on the damaged airfoil.     

Concentration Dependent Structural,Morphological, Spectral,Optical and Electrical Properties of Spray Pyrolyzed NiO thin films

Silicon - Nickel oxide (NiO) thin films were prepared by spray pyrolysis technique using a solution of nickel (II) chloride hexahydrate (NiCl2.6H2O) and distilled water on glass substrates. The...     

Origin of Microstructural Irreversibility in Ni-Ti Based Shape Memory Alloys during Thermal Cycling

Different microstructures of Ni-Ti- and Ni-Ti-Fe-based shape memory alloys were subjected to thermal cycling: dipping in liquid nitrogen, for approximately 5 minutes, and then bringing it back to room temperature or austenite (cubic: B2) ↔ martensite (monoclinic: B19′) reversible solid-state phase transformation. Direct electron backscattered diffraction (EBSD) observations could bring out aspects of microstructural irreversibilities: namely, changes in grain size, misorientation buildup, and presence of retained martensite. The average changes in grain size (Δd) differed by almost 2 to 4 times between different microstructures. The highest Δd was typically observed in structures having maximum clustering of fine (d < 5 μm) grains. The sample with highest Δd was also subjected to multiple thermal cycling. Although Δd scaled linearly with d after the first thermal cycle, the scatter increased during subsequent thermal cycles. Grain or orientations deviating from the linear behavior were clearly anisotropic crystallographically. With repeated thermal cycling, the patterns of changes in Δd, austenite misorientation, and retained martensite content were similar. A phenomenological model or hypothesis, based on 40 deg á 001 ñ \left\langle {001} \right\rangle orientation relationship between austenite and martensite phases, was proposed to address the observed patterns of microstructural irreversibility.     

Nonstructural C protein is required for efficient measles virus replication in human peripheral blood cells

The P gene of measles virus (MV) encodes the phosphoprotein, a component of the virus ribonucleoprotein complex, and two nonstructural proteins, C and V, with unknown functions. Growth of recombinant MV, defective in C or V expression, was explored in human peripheral blood mononuclear cells (PBMC). The production of infectious recombinant MV V- was comparable to that of parental MV tag in simian Vero fibroblasts and in PBMC. In contrast, MV C- progeny was strongly reduced in PBMC but not in Vero cells. Consistently, the expression of both hemagglutinin and fusion proteins, as well as that of nucleoprotein mRNA, was lower in MV C--infected PBMC. Thus, efficient replication of MV in natural host cells requires the expression of the nonstructural C protein. The immunosuppression that accompanies MV infection is associated with a decrease in the in vitro lymphoproliferative response to mitogens. MV C- was as potent as MV tag or MV V- in inhibiting the phytohemagglutinin-induced proliferation of PBMC, indicating that neither the C protein nor the V protein is directly involved in this effect.     

Synthesis and characterization of layered and scrolled amine-templated vanadium oxides

In order to fully understand the formation mechanism, structure, and role of structural curvature of vanadium oxide nanotubes (VONTs), two isostructural materials (one planar and the other curved)—ethylenediammonium (enH₂) intercalated V₇O₁₆ and vanadium oxide nanourchins (VONUs)—were synthesized and characterized via X-ray diffraction (XRD), electron microscopy, thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy, and magnetic measurements. The synthesis route to (enH₂)V₇O₁₆ is developed using vanadium pentoxide as a starting material and employing pH control. VONUs are synthesized using n-dodecylamine as an amine template for the first time. We demonstrate that the structure of the vanadium oxide layer in these compounds is similar to that of VONTs and their magnetic properties all fit to the same model including the temperature-independent, Curie–Weiss, and spin ½ antiferromagnetic dimer contributions. The vanadium oxidation state in tubular structures appears to be higher than in planar compounds such as (eH₂)V₇O₁₆ and BaV₇O₁₆. The role of the template and vanadium reduction in the formation of nanotubes is discussed.     

Damage detection of a rotating cracked shaft using an active magnetic bearing as a force actuator - analysis and experimental verification

The active health monitoring of rotordynamic systems in the presence of breathing shaft cracks is considered in this work. The shaft is assumed to be supported by conventional bearings, and the active magnetic bearing (AMB) is used in a midshaft or outboard location as an actuator to apply specified, time-dependent forcing on the system. These forces, if properly chosen, induce a combination resonance that can be used to identify the magnitude of the time-dependent stiffness arising from the breathing mode of the shaft crack. The technique is verified experimentally on a high speed test rotor with a healthy and a cracked shaft.     

Modification of CaO by Organic Alumina Precursor for Enhancing Cyclic Capture of CO2 Greenhouse Gas

The modification of CaO sorbent with organic alumina precursor to enhance the sorption capacity during cyclic capture is demonstrated in this study. The results indicate that during the 10?min sorption time for each cycle, the CO2 sorption capacity of original CaO sorbent is significantly decreased from 0.27 to 0.19 and 0.12?g CO2/g sorbent after 5 and 60?cycles, respectively. On the other hand, the organic alumina modified CaO has a fresh capacity of 0.22?g CO2/g sorbent, it increases to 0.24?g CO2/g sorbent after 5?cycles, and then decreases to around 0.15?g CO2/g sorbent after 60?cycles. When increasing the sorption time to 60?min at the 66th cycle, the sorption capacity of original CaO is 0.2, whereas it is 0.26?g CO2/g sorbent for organic alumina modified CaO. The results demonstrate that by adding only 5% by weight of Ca12Al14O33 species into the CaO sorbent, the CO2 sorption capacity can be enhanced up to ～ 27% by weight.