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Mycobacterium tuberculosis (Mtb) isocitrate lyase (ICL) is an established drug target that facilitates Mtb persistence. Unlike other mycobacterial strains, where ICL2 is a single gene product, H37Rv has a split event, resulting in two tandemly coded icls - rv1915 and rv1916. Our recent report on functionality of individual Rv1915 and Rv1916, led to postulate the cooperative role of these proteins in pathogen's survival under nutrient-limiting conditions. This study investigates the possibility of Rv1915 and Rv1916 interacting and forming a complex. Pull down assay, activity assay, mass spectrometry and site directed mutagenesis was employed to investigate and validate Rv1915-Rv1916 complex formation. Rv1915 and Rv1916 form a stable complex in vitro, with enhanced ICL/MICL activities as opposed to individual proteins. Further, activities monitored in the presence of acetyl-CoA show significant increase for Rv1916 and the complex but not of Rv0467 and Rv1915Δ90CT. Both full length and truncated Rv1915Δ90CT can form complex, implying the absence of its C-terminal disordered region in complex formation. Further, in silico analysis and site-directed mutagenesis studies reveal Y64 and Y65 to be crucial residues for Rv1915-Rv1916 complex formation. This study uncovers the association between Rv1915 and Rv1916 and supports the role of acetyl-CoA in escalating the ICL/MICL activities of Rv1916 and Rv1915Δ90CT-Rv1916 complex. Partitioning of ICL2 into Rv1915 and Rv1916 that associates to form a complex in Mtb H37Rv, suggests its importance in signaling and regulation of metabolic pathway particularly in carbon assimilation. • Rv1915 and Rv1916 of Mtb H37Rv associate together to form in vitro protein-protein complex. • Deletion of disordered C-terminal of Rv1915 does not abrogate complex formation with Rv1916. • Site-directed mutagenesis studies show Y64 and Y65 residues of Rv1916 to be crucial for complex formation. • The presence of acetyl-CoA increases the ICL and MICL activities of Rv1916 and the complex. [ABSTRACT FROM AUTHOR]

Nickel–cobalt–zinc ferrites, Ni0.2Co x Zn0.8−x Fe2O4 (with x=0, 0.2, 0.4, 0.6, 0.8,) have been prepared using the auto-combustion method. X-ray diffraction, Fourier transform infrared (FT-IR) and Raman spectroscopy confirmed the cubic spinel structure of the ferrites. Microwave dielectric constant (ε r ) and quality factor (Q×f) were measured by using the Hakki–Coleman technique. Dielectric constant calculated using the Clausius–Mossoitti relation showed good agreement with the experimental value. Relative permeability of the ferrites was calculated by using the Nicholson–Ross–Weir conversion technique. Dielectric constant (ε r ) decreased from 7.474 to 5.548 and temperature coefficient of resonant frequency (τ f ) increased from −75.85ppm/°C to −19.32ppm/°C, respectively, and relative permeability increased from 2.1085 to 3.2179 with increase in Cobalt content. The composition Ni0.2Co0.2Zn0.6Fe2O4 was used to develop ferrite resonator antennas (FRA) and was studied in cylindrical, triangular and cuboid shapes with co-axial probe feeding mechanisms. The antenna characteristics were simulated using high frequency structure simulation (HFSS) software and a good agreement has been achieved between the measured and simulated results. The cuboid shaped FRA show maximum bandwidth of 990MHz, while the cylindrical shaped FRA show a maximum gain of 3.48dB, respectively. [ABSTRACT FROM AUTHOR]

In this paper a novel feeding technique is presented using transition between microstrip-line segment and folded substrate integrated waveguide (FSIW), which provides very low insertion loss over wide frequency band and can be used for signal feeding in FSIW based waveguides and components. Concept of simultaneous transformation in mode and impedance by tapering central metal septum and removing upper ground plane precisely above the tapering over the transition section is used to design the novel transitions. The presented design procedures are applied on transitions for FSIW transmission lines operating in different frequency bands from C to K band. The concept is explained in detail with an example for transitions designed for FSIW operating in Ku band. All the designed structures are simulated using HFSS software. The designed FSIW with the transitions operating in Ku band is fabricated and the measured results are compared with simulated results and are found in good agreement. Dimensions of transitions designed for FSIWs operating in other frequency bands are tabulated. [ABSTRACT FROM AUTHOR]

Objectives: Remote patient monitoring became critical for patients receiving cancer treatment during the COVID-19 pandemic. We sought to test feasibility of an electronic patient symptom management program implemented during a pandemic. We collected and analyzed the real-world data to inform practice quality improvement and understand the patient experience.Methods: Eligible patients had breast, lung, or ovarian cancers, multiple myeloma, or acute myeloid leukemia and 12 weeks of planned chemotherapy. Patients were notified that a symptom survey with common symptoms derived from the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was available to complete using a smart phone, tablet, or computer. Patients recorded their symptoms and results were sent to the provider. Patients received care guidelines for mild/moderate severity symptoms and a phone call from the provider for severe reports.Results: A total of 282 patients generated > 119 088 data points. Patients completed 2860 of 3248 assigned surveys (88%), and 152 of 282 patients (54%) had symptom reports that generated an immediate notification to the provider. Longitudinal data were analyzed to determine whether previous reports predicted a notification alert and whether symptoms resolved after the alert was addressed.Conclusions: An electronic patient symptom management program was implemented in the midst of the COVID-19 pandemic. Enrollment of 282 patients and a high survey completion (88%) demonstrated feasibility/acceptance. Patients reported symptoms at severe levels of 54% of the time and received self-management instructions and provider phone calls that resolved or decreased the severity of the symptom. A standard approach and validated instrument provide opportunities for improving and benchmarking outcomes. [ABSTRACT FROM AUTHOR]

Abstract: In this paper the structural and microwave dielectric properties of the (1− x)(Mg0.95Zn0.05)TiO3–(x)(Ca0.6La0.8/3)TiO3 ceramic composites have been investigated with the variation of x as well as sintering temperature. The grown samples have been characterized by means of X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray (EDX) spectroscopy analysis. The Rietveld analysis of the XRD data has been carried out for structure refinement of the phases. The relative permittivity , quality factor (Q) and temperature coefficient of resonant frequency τf of the grown samples have been thoroughly studied. Out of all samples of this series, the sample with x =0.21 shows excellent dielectric properties with , Q × f ∼60,738GHz (at 6.44GHz) and a nearly zero τf ∼−0.8ppm/°C. Two types of dielectric resonator antennas with different feeding mechanisms have been fabricated using this sample to study their performance. The experimental results have been compared with the simulated results obtained using Ansoft High Frequency Structure Simulator software. [Copyright &y& Elsevier]

Abstract: This paper presents the design of a cylindrical dielectric resonator antenna (DRA) using a nearly temperature stable dielectric composite material. By the combination of compounds with positive and negative temperature coefficient, a dielectric composite series (1− x)(Mg0.95Zn0.05)TiO3 − x(Ca0.8Sr0.2)TiO3 has been developed. The structural and morphological properties of the grown samples have been characterized by means of X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray (EDX) spectroscopy analysis. Microwave dielectric properties of the composite samples have been investigated using the TE01δ dielectric resonator method. Relative permittivity (ɛ r ) of 21.9, dielectric loss tan δ of 0.0002 and temperature coefficient of resonant frequency (τ f ) of −0.15ppm/°C have been obtained for the x =0.08 sample, which was used for designing the DRA. The DRA resonates at 4.6GHz frequency and offers the bandwidth of 315MHz. The characteristics of proposed DRA have been simulated using the Ansoft high frequency structure simulator (HFSS). Comparison between the simulated and measured results shows a reasonably good agreement. [Copyright &y& Elsevier]

• Cloning, purification and biochemical characterization of CysE from Klebsiella pneumoniae • 3-D crystal structure of Kpn CysE complexed with L-cysteine at 2.8 Å • In silico identification and in vitro validation of inhibitory potential of quercetin • Identification of an allosteric site at the trimer-trimer interface in the hexameric CysE The emergence and spread of multidrug-resistant strains of Klebsiella pneumoniae is a major concern that necessitates the development of unique therapeutics. The essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery. In this study, as an initial step to structure-based drug discovery, CysE from K. pneumonia was structurally and biochemically characterized. Subsequently, blind docking of selected natural products into the X-ray crystallography determined 3D structure of the target was carried out. Experimental validation of the inhibitory potential of the top-scorers established quercetin as an uncompetitive inhibitor of Kpn CysE. Molecular dynamics simulations carried out to elucidate the binding mode of quercetin reveal that this small molecule binds at the trimer-trimer interface of hexameric CysE, a site physically distinct from the active site of the enzyme. Detailed analysis of conformational differences incurred in Kpn CysE structure on binding to quercetin provides mechanistic understanding of allosteric modulation. Binding of quercetin to CysE leads to conformation changes in the active site loops and proximal loops that affect its internal dynamics and consequently its affinity for substrate/co-factor binding, justifying the reduced enzyme activity. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is one of the leading causes of death worldwide. Long duration of TB therapy, results in the persistence and development of drug resistant strains of causative organism Mycobacterium tuberculosis (Mtb). Novel drug targets against persistent Mtb is an immediate need for overcoming this global menace. Isocitrate lyase (ICL), the first enzyme of glyoxylate pathway, is essential for persistent Mtb and absent in humans, hence a propitious target for drug development. Pathogenic Mtb H37Rv, have two types of ICLs - ICL1 encoded by icl (Rv0467) is well characterized and homologous to eubacterial enzyme whereas ICL2 encoded by aceA is more related to eukaryotic isocitrate lyase. To compound it, the aceA gene is split into two ORFs namely rv1915 / aceAa and rv1916 / aceAb. No translational product has been reported for the later and therefore, in vivo existence of Rv1916/ICL2 b is debatable. This study reports recombinant production of Rv1916 in heterologous host E. coli BL21 (DE3) for structure function studies. The studies categorically demonstrate that akin to Mtb ICL1, recombinant Rv1916 also possess dual ICL and methylisocitrate lyase (MICL) activities in vitro. Based on in silico analysis, a putative function linked to secondary metabolite synthesis is assigned to unique mycobacterial domain IV. • This study is the first report of Rv1916 possessing in vitro ICL and MICL activities. • 3-Nitropropionate is an uncompetitive inhibitor of both the activities. • Phylogenetic analysis suggests, evolutionary relationship between Rv1916 and ICLs of some soil bacterial species. • Domain IV of Rv1916, is hypothesized to be involved in synthesis of secondary metabolites. [ABSTRACT FROM AUTHOR]

Drug resistance to almost all antibiotics of Shigella flexneri , a major cause of shigellosis in developing countries, necessitates continuous discovery of novel therapeutics. This study reports a structure-function analysis of a potential drug target serine acetyltransferase (CysE), an enzyme of de novo cysteine biosynthesis pathway that is absent in humans. Analysis of CysE sequences of S. flexneri species and serotypes displayed only two variants that differed by a single amino acid substitution at position 241. Structural inspection of the available crystal structure disclosed this site to be distinct from the substrate/cofactor binding pockets or dimer/trimer interfaces. This study discovers that V241 variant of S. flexneri CysE has nearly null enzymatic activity. The observation is explained by molecular dynamic studies which reveal that the disorder generated by A241V substitution is the basis of dissociation of the quaternary assembly of S. flexneri CysE leading to loss of enzymatic activity and stability. The study provides the first evidence that position 241 of CysE, affects the catalytic efficiency of enzyme and suggests this locus as a ‘hot spot’ for the propagation of conformational changes. It may be postulated that transient quaternary structure of CysE maybe another mechanism for regulating the intracellular level of cysteine. [ABSTRACT FROM AUTHOR]

This paper reports the study of structural, morphological and microwave dielectric properties of ( Mg 1 − x Co x ) 4 Ta 2 O 9 ( x = 0 – 0.6 ) ceramics, sintered at 1300–1400 °C. The grown samples were characterized by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy. Microwave dielectric properties of these samples were investigated using the TE 01 δ dielectric resonator method. Our study shows that the dielectric properties are strongly dependent on the compositions, densification and micro-structure of the specimens. Out of these compositions, ( Mg 0 . 7 Co 0 . 3 ) 4 Ta 2 O 9 shows near zero τ f with a dielectric constant ϵ r ~ 13.79 and a quality factor Qf ~ 56,876 GHz (measured at 8.93 GHz). On a substrate made up of this ceramic, a low pass filter of 2.6 GHz cut-off was simulated using Sonnet Lite software and then fabricated. The measured results show a reasonably good agreement with the simulated results. This dielectric shows ~68% size reduction as comparison to FR4 substrate for the same filter design. [ABSTRACT FROM AUTHOR]

The potential allergenicity of Bar, Barnase, and Barstar recombinant proteins expressed in genetically engineered mustard for pollination control in plant breeding was evaluated for regulatory review. To evaluate the potential allergenicity of the Bar, Barnase and Barstar proteins amino acid sequence comparisons were made to those of known and putative allergens, and search for published evidence to the sources of the genes using the AllergenOnline.org database. Initial comparisons in 2012 were performed with version 12 by methods recommended by the Codex Alimentarius Commission and the Indian Council of Medical Research, Government of India. Searches were repeated with version 15 in 2015. A literature search was performed using PubMed to identify reports of allergy associated with the sources of the three transgenes. Potential open reading frames at the DNA insertion site were evaluated for matches to allergens. No significant sequence identity matches were identified with Bar, Barnase or Barstar proteins or potential fusion peptides at the genomic-insert junctions compared to known allergens. No references were identified that associated the sources of the genes with allergy. Based on these results we conclude that the Bar, Barnase and Barstar proteins are unlikely to present any significant risk of food allergy to consumers. [ABSTRACT FROM AUTHOR]