Multifarious transparent glass nanocrystal composites

Glasses comprising well known ferroelectric crystalline phases have been a subject of curious investigation from the point of view of exploiting these composites for dielectric, pyroelectric, ferroelectric, electro and non-linear optical devices. Transparent glass-ceramics containing ferroelectric crystallites at nano scale have been of much interest owing to their promising physical properties. The advantages that are associated with glass-ceramics include very low levels of porosity and hence high break down voltages. It is of our interest to nanocrystallize Aurivillius family of ferroelectric oxides and tetragonal tungsten bronzes on borate and tellurite based glass matrices and demonstrate their promising optical and nonlinear optical properties. Apart from the above, the nanocrystallites of well known ferroelectric material LiNbO3 was grown in a reactive glass matrix. These nanocrystals of LiNbO3 exhibited intense second harmonic signals in transmission mode when exposed to IR light at 1064 nm. The most interesting result was the demonstration of optical diffraction of the second harmonic signals which was attributed to the presence of self- organized sub-micrometer sized LiNbO3 crystallites that were indeed inscribed by the IR laser light which was used to probe in the NLO property of these materials

Identification of critical residues in loop E in the 5-HT(3AS)R binding site

BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family. RESULTS: Thirteen amino acids in the mouse 5-HT(3AS)R that correspond to the putative E binding loop of the nicotinic α7 receptor were chosen for mutagenesis. Due to the presence of a highly conserved glycine in this region, it has been suggested that this binding loop is comprised of a hairpin turn and may form a portion of the ligand-binding site in this ion channel family. Mutation of the conserved glycine (G147) to alanine eliminated binding of the 5-HT(3)R antagonist [(3)H]granisetron. Three tyrosine residues (Y140, Y142 and Y152) also significantly altered the binding of 5-HT(3)R ligands. Mutations in neighboring residues had little or no effect on binding of these ligands to the 5-HT(3AS)R. CONCLUSION: Our data supports a role for the putative E-loop region of the 5-HT(3)R in the binding of 5-HT, mCPBG, d-tc and lerisetron. 5-HT and mCPBG interact with Y142, d-tc with Y140 and lerisetron with both Y142 and Y152. Our data also provides support for the hypothesis that this region of the receptor is present in a loop structure

Variation of Radon Progeny Concentration over a Continental Location

Background: The variation of the radon progeny concentration in outdoor environment and meteorological parameters at fine resolution were studied for one year at a continental location, National Atmospheric Research Laboratory, Gadanki, India.Materials and Methods: The concentrations were measured using Alpha Progeny Meter by collecting air samples at a height of 1 m above the Earth’s surface at a known flow rate. Results: Radon progeny concentration shows temporal variations on diurnal and monthly scales, and is due to mixing in the atmosphere. Peak in the early morning hours and low values during afternoon compared to nighttime are due to differential heat contrast between earth’s surface and its atmosphere. However, the activity during February shows maximum compared to June/July months.The diurnal variation of radon progeny shows positive correlation with the relative humidity and negative correlation with ambient temperature.The monthly mean activity of radon progeny for the year 2012 was found to be 4.76 ± 0.73 mWL. Conclusion: The mean concentration of radon progeny in the study region is relatively high compared to the other locations in India and may be due to the rocky terrains and trapping of air-masses near the observation site due to its topography

External, internal and semi-internal vibrations in molecular solids: spectroscopic criteria for identification

A new method to identify the nature of vibrations in molecular crystals as external or internal is proposed. The criterion is that in isotropic mixed crystals of protonated and corresponding perdeuterated compounds, the external motions (phonons) are in the amalgamation limit, while the internal modes, and the "semi-internal" methyl torsions, are usually in the separated band limit. This criterion is supported by experimental isotopic mixed crystal studies of many molecular crystals. Previous criteria, like temperature and isotope shifts, are shown to be less reliable. Anthracene and biphenyl Raman spectra, as well as literature data, are used as illustrations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33821/1/0000078.pd

A digital twin framework for predictive maintenance in industry 4.0

The rapid advancements in manufacturing technologies are transforming the current industrial landscape through Industry 4.0, which refers not only to the integration of information technology with industrial production, but also to the use of innovative technologies and novel data management approaches. The target is to enable the manufacturers and the entire supply chain to save time, boost productivity, reduce waste and costs, and respond flexibly and efficiently to consumers’ requirements. Industry 4.0 moves the digitization of manufacturing components and processes a step further by creating smart factories. Within this context, one of the key enabling technologies for Industry 4.0 is the adoption and integration of the Digital Twin (DT). However, most of the DT solutions provided by the current leading vendors are in fact digital models or digital shadows, and not digital twins. This is due to the fact that there is no common understanding of the definition of the DT amongst the leading vendors, and its usage is slightly different but showcased under the same umbrella of DT. In this paper, a DT framework is proposed that replicates the processes of a real production line for product assembly using the Festo Cyber Physical Factory for Industry 4.0 located at Middlesex University. Moreover, the paper introduces a viable framework for interlinking the physical system with its digital instance in order to offer extended predictive maintenance services and form a fully integrated digital twin solution

Functional group interactions of a 5-HT3R antagonist

Background: Lerisetron, a competitive serotonin type 3 receptor (5-HT 3R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT3R binding site. Site directed mutagenesis studies of the 5-HT3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site. Results: Two analogs of lerisetron were synthesized to probe 5-HT3R functional group interactions with this compound. Analog 1 lacks the N1 benzyl group of lerisetron and analog 2 contains oxygen in place of the distal piperazine nitrogen. Both analogs show significantly decreased binding affinity to wildtype 5-HT3ASRs. Mutations at W89, R91, Y142 and Y152 produced significant decreases in binding compared to wildtype receptors. Binding affinities of analogs 1 and 2 were altered only by mutations at W89, and Y152. Conclusions: Based on the data obtained for lerisetron and analogs 1 and 2, we have proposed a tentative model of the lerisetron binding pocket of the 5-HT3ASR. According to this model, The N-benzyl group interacts in a weak interaction with R91 while the benzimidazole group interacts with W89. Our data support an interaction of the distal amino nitrogen with Y142 and Y152

Functional group interactions of a 5-HT(3)R antagonist

BACKGROUND: Lerisetron, a competitive serotonin type 3 receptor (5-HT(3)R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT(3)R binding site. Site directed mutagenesis studies of the 5-HT(3A)R have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site. RESULTS: Two analogs of lerisetron were synthesized to probe 5-HT(3)R functional group interactions with this compound. Analog 1 lacks the N1 benzyl group of lerisetron and analog 2 contains oxygen in place of the distal piperazine nitrogen. Both analogs show significantly decreased binding affinity to wildtype 5-HT(3AS)Rs. Mutations at W89, R91, Y142 and Y152 produced significant decreases in binding compared to wildtype receptors. Binding affinities of analogs 1 and 2 were altered only by mutations at W89, and Y152. CONCLUSIONS: Based on the data obtained for lerisetron and analogs 1 and 2, we have proposed a tentative model of the lerisetron binding pocket of the 5-HT(3AS)R. According to this model, The N-benzyl group interacts in a weak interaction with R91 while the benzimidazole group interacts with W89. Our data support an interaction of the distal amino nitrogen with Y142 and Y152

Digital twins: a survey on enabling technologies, challenges, trends and future prospects

Digital Twin (DT) is an emerging technology surrounded by many promises, and potentials to reshape the future of industries and society overall. A DT is a system-of-systems which goes far beyond the traditional computer-based simulations and analysis. It is a replication of all the elements, processes, dynamics, and firmware of a physical system into a digital counterpart. The two systems (physical and digital) exist side by side, sharing all the inputs and operations using real-time data communications and information transfer. With the incorporation of Internet of Things (IoT), Artificial Intelligence (AI), 3D models, next generation mobile communications (5G/6G), Augmented Reality (AR), Virtual Reality (VR), distributed computing, Transfer Learning (TL), and electronic sensors, the digital/virtual counterpart of the real-world system is able to provide seamless monitoring, analysis, evaluation and predictions. The DT offers a platform for the testing and analysing of complex systems, which would be impossible in traditional simulations and modular evaluations. However, the development of this technology faces many challenges including the complexities in effective communication and data accumulation, data unavailability to train Machine Learning (ML) models, lack of processing power to support high fidelity twins, the high need for interdisciplinary collaboration, and the absence of standardized development methodologies and validation measures. Being in the early stages of development, DTs lack sufficient documentation. In this context, this survey paper aims to cover the important aspects in realization of the technology. The key enabling technologies, challenges and prospects of DTs are highlighted. The paper provides a deep insight into the technology, lists design goals and objectives, highlights design challenges and limitations across industries, discusses research and commercial developments, provides its applications and use cases, offers case studies in industry, infrastructure and healthcare, lists main service providers and stakeholders, and covers developments to date, as well as viable research dimensions for future developments in DTs

Structure-Based Exploration and Exploitation of the S4 Subsite of Norovirus 3CL Protease in the Design of Potent and Permeable Inhibitors

Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents. We hypothesized that the S4 subsite of the enzyme may provide an effective means of designing potent and cell permeable inhibitors of the enzyme. We report herein the structure-guided exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design and synthesis of effective inhibitors of the protease