Optimization of friction stir welding process to maximize tensile strength of AA6061/ZrB<Subscript>2</Subscript> in-situ composite butt joints

A variety of ceramic particles is added to aluminum alloys to produce aluminum matrix composites (AMCs). Establishing the joining procedure for AMCs is an essential requirement prior to extending their applications. Friction stir welding (FSW) is an emerging solid state welding which eliminates all the defects associated with fusion welding of AMCs. An attempt has been made to friction stir weld AA6061/ ZrB₂ in-situ composite. A four factor, five level central composite rotatable design has been used to minimize the number of experiments. The four factors considered are tool rotational speed, welding speed, axial force and weight percentage of ZrB₂. A mathematical model has been developed incorporating the FSW process parameters to predict the ultimate tensile strength (UTS) and FS process is optimized using generalized reduced gradient method (GRG) to maximize the UTS. The effect of process parameters on UTS was analyzed. It was observed that the process parameters independently influence the UTS over the entire range studied in this work.     

Development of an Efficient G‐Quadruplex‐Stabilised Thrombin‐Binding Aptamer Containing a Three‐Carbon Spacer Molecule

The thrombin‐binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G‐quadruplex‐forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three‐carbon spacer (spacer‐C₃), unlocked nucleic acid (UNA) and 3′‐amino‐modified UNA (amino‐UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G‐quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer‐C₃ introduction at the T7 loop position (TBA‐SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA‐SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties.     

Thiophene-Based Dual Modulators of Aβ and Tau Aggregation

Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and Tau aggregates in the brain, which induces various pathological events resulting in neurodegeneration. There have been continuous efforts to develop modulators of the Aβ and Tau aggregation process to halt or modify disease progression. A few small-molecule-based inhibitors that target both Aβ and Tau pathology have been reported. Here, we report the screening of a targeted library of small molecules to modulate Aβ and Tau aggregation together with their in vitro, in silico and cellular studies. In vitro ThT fluorescence assay, dot blot assay, gel electrophoresis and transmission electron microscopy (TEM) results have shown that thiophene-based lead molecules effectively modulate Aβ aggregation and inhibit Tau aggregation. In silico studies performed by employing molecular docking, molecular dynamics and binding-free energy calculations have helped in understanding the mechanism of interaction of the lead thiophene compounds with Aβ and Tau fibril targets. In cellulo studies revealed that the lead candidate is biocompatible and effectively ameliorates neuronal cells from Aβ and Tau-mediated amyloid toxicity.     

Structure and redox properties of the haem centre in the C357M mutant of cytochrome P450cam

The effects of site-specific mutation of the axial cysteine (C357M) to a methionine residue in cytochrome P450cam on the enzyme's coordination geometry and redox potential have been investigated. The absorption spectra of the haem centre in the C357M mutant of the enzyme showed close similarity to those of cytochrome c both in the oxidised and reduced forms. A well-defined absorption peak at 695 nm, similar to that seen in the case of cytochrome c and characteristic of methionine ligation to the ferric haem, was observed. The results indicated that the haem of C357M cytochrome P450cam is possibly axially coordinated to a methionine and a histidine, analogously to cytochrome c. The circular dichroism spectra in the visible and the far-UV regions suggested that the tertiary structure of the haem cavity in the C357M mutant cytochrome P450cam was distinctly different from that in the wild-type enzyme or in cytochrome c, although the secondary structure of the mutant remained identical to that of the wild-type cytochrome P450cam. Comparison of the natures of the CD spectra in the 400 nm and 695 nm regions of the C357M mutant of cytochrome P450cam with those of horse cytochrome c suggested (R) chirality at the sulfur atom of the iron-bound methionine residue in the mutant. The redox potential of the haem centre, estimated by redox titration of the C357M mutant, was found to be +260 mV, which is much higher than that in the wild-type enzyme and similar to the redox potential of cytochrome c. This supported the concept that axial ligation of the haem plays the major role in tuning the redox potential of the haem centre in haem proteins.     

Gaussian Mixture Modeling of Short-Time Fourier Transform Features for Audio Fingerprinting

In audio fingerprinting, an audio clip must be recognized by matching an extracted fingerprint to a database of previously computed fingerprints. The fingerprints should reduce the dimensionality of the input significantly, provide discrimination among different audio clips, and, at the same time, be invariant to distorted versions of the same audio clip. In this paper, we design fingerprints addressing the above issues by modeling an audio clip by Gaussian mixture models (GMM). We evaluate the performance of many easy-to-compute short-time Fourier transform features, such as Shannon entropy, Renyi entropy, spectral centroid, spectral bandwidth, spectral flatness measure, spectral crest factor, and Mel-frequency cepstral coefficients in modeling audio clips using GMM for fingerprinting. We test the robustness of the fingerprints under a large number of distortions. To make the system robust, we use some of the distorted versions of the audio for training. However, we show that the audio fingerprints modeled using GMM are not only robust to the distortions used in training but also to distortions not used in training. Among the features tested, spectral centroid performs best with an identification rate of 99.2% at a false positive rate of 10^-4. All of the features give an identification rate of more than 90% at a false positive rate of 10^-3