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NU-6027 Inhibits Growth of Mycobacterium tuberculosis by Targeting Protein Kinase D and Protein Kinase G
No full textTuberculosis (TB) is a global health concern, and this situation has further worsened due to the emergence of drug-resistant strains and the failure of BCG vaccine to impart protection. There is an imperative need to develop highly sensitive, specific diagnostic tools, novel therapeutics, and vaccines for the eradication of TB. In the present study, a chemical screen of a pharmacologically active compound library was performed to identify antimycobacterial compounds. The phenotypic screen identified a few novel small-molecule inhibitors, including NU-6027, a known CDK-2 inhibitor. We demonstrate that NU-6027 inhibits Mycobacterium bovis BCG growth in vitro and also displayed cross-reactivity with Mycobacterium tuberculosis protein kinase D (PknD) and protein kinase G (PknG). Comparative structural and sequence analysis along with docking simulation suggest that the unique binding site stereochemistry of PknG and PknD accommodates NU-6027 more favorably than other M. tuberculosis Ser/Thr protein kinases. Further, we also show that NU-6027 treatment induces the expression of proapoptotic genes in macrophages. Finally, we demonstrate that NU-6027 inhibits M. tuberculosis growth in both macrophage and mouse tissues. Taken together, these results indicate that NU-6027 can be optimized further for the development of antimycobacterial agents
Palladium-induced transformation of nematic liquid crystals to robust metallogel comprising self-assembled nanowires
No full textThe formation of a nematic liquid-crystalline phase in the bulk along with gelation of a novel asymmetric bolaamphiphilic NDI scaffold has been demonstrated. Further, a discrete metal NDI complex that is capable of forming a robust metallogel through wrapping of the NDI core with the oxyethylene chains of the neighboring molecules has been synthesized
ATR Signaling Uncouples the Role of RAD51 Paralogs in Homologous Recombination and Replication Stress Response
No full textATR kinase-mediated replication checkpoint is vital for genome maintenance following replication stress. Previously, we showed that XRCC2-RAD51D (DX2) sub-complex of RAD51 paralogs restrains active DNA synthesis during dNTP alterations, in a manner dependent on ATR-mediated phosphorylation of XRCC2. Here, we find that unrestrained fork progression in XRCC2 deficiency and phosphorylation defect causes replication-associated errors, subsequently resulting in genome-wide double-strand breaks (DSBs) and early activation of ATM signaling. Cells defective in XRCC2 phosphorylation exhibit ATM/ATR-mediated early activation of XRCC3 during perturbed replication, which facilitates recombination-mediated repair of the post-replicative DNA damage and thereby promotes cell viability. Collectively, our findings identify collaborative roles of RAD51 paralog complexes during replication stress and reveal their differential regulation by ATR signaling to promote cell survival and genome integrity
Large emission enhancement and emergence of strong coupling with plasmons in nanoassemblies: Role of quantum interactions and finite emitter size
No full textThe Purcell effect has been the basis for several decades in understanding enhancement of photonic efficiency and decay rates of emitters through their coupling to cavity modes and metal nanostructures. However, it is not clear whether this regime of radiative enhancements can be extended to ultrasmall nanoparticle sizes or interparticle distances. Here we report large radiative enhancements of quantum dot assemblies with extremely small metal nanoparticles and emitter-particle separations R of a few nanometers, where Purcell effect would lead to either no enhancements or quenching. We invoke a new regime of radiative enhancements to explain the experimental data and also correctly predict the emergence of strong coupling below certain R, as observed in experiments. In addition, we show that the widely used point emitter approximations diverge from actual observations in the case of finite size emitters at such small separations
Measurement of the hysteretic thermal properties of W-doped and undoped nanocrystalline powders of VO2
No full textHysteresis loops exhibited by the thermal properties of undoped and 0.8 at.%W-doped nanocrystalline powders of VO2 synthesized by means of the solution combustion method and compacted in pellets, are experimentally measured by phototherma I radiometry. It is shown that: (i) the W doping reduces both the hysteresis loops of VO2 and its transition temperature up to 15 degrees C. (ii) The thermal diffusivity decreases (increases) until (after) the metallic domains become dominant in the VO2 insulating matrix, such that its variation across the metal-insulation transition is enhanced by 23.5% with W-0.8 at.% doping. By contrast, thermal conductivity (thermal effusivity) increases up to 45% (40%) as the metallic phase emerges in the VO2 structure due to the insulator-to-metal transition, and it enhances up to 11% (25%) in the insulator state when the local rutile phase is induced by the tungsten doping. (iii)The characteristic peak of the VO2 specific heat capacity is observed in both heating and cooling processes, such that the phase transition of the 0.8 at.%W-doped sample requires about 24% less thermal energy than the undoped one. (iv) The impact of theW doping on the four above-mentioned thermal properties ofVO(2) mainly shows up in its insulator phase, as a result of the distortion of the local lattice induced by the electrons of tungsten. W doping at 0.8 at.% thus enhances the VO2 capability to transport heat but diminishes its thermal switching efficiency
Search for pair production of vectorlike quarks in the fully hadronic final state
No full textThe results of two searches for pair production of vectorlike T or B quarks in fully hadronic final states are presented, using data from the CMS experiment at a center-of-mass energy of 13 TeV. The data were collected at the LHC during 2016 and correspond to an integrated luminosity of 35.9 fb(-1). A cut-based analysis specifically targets the bW decay mode of the T quark and allows for the reconstruction of the T quark candidates. In a second analysis, a multiclassification algorithm, the ``boosted event shape tagger,'' is deployed to label candidate jets as originating from top quarks, and W, Z, and H. Candidate events are categorized according to the multiplicities of identified jets, and the scalar sum of all observed jet momenta is used to discriminate signal events from the quantum chromodynamics multijet background. Both analyses probe all possible branching fraction combinations of the T and B quarks and set limits at 95% confidence level on their masses, ranging from 740 to 1370 GeV. These results represent a significant improvement relative to existing searches in the fully hadronic final state
Interdiffusion study of the topologically closed packed phase and the phase boundary compositions in the Fe-Mo system
No full textFe/Mo bulk diffusion couples are annealed at 1050-1200 degrees C to study the growth and diffusion behaviour of mu phase in the Fe-Mo system. Parabolic growth constants and integrated interdiffusion coefficients are determined in the mu phase. The activation energies for the growth of mu phase and for the integrated interdiffusion coefficients are estimated as 228 +/- 22 and 733 +/- 10 kJ/mol, respectively. The relatively high activation energy for interdiffusion in mu phase, determined at high homologous temperature of 0.8-0.9, indicates that mu phase grows by lattice diffusion. Phase boundary compositions, measured by EPMA, indicates the homogeneity range of mu phase to be similar to 3 at.% higher towards the Fe-rich side (i.e., 36 at.% Mo) as compared to the reported composition of 39-44 at.% Mo in the phase diagram
An Overview of Hydrogel-Based Bioinks for 3D Bioprinting of Soft Tissues
No full textIt has been widely perceived that three-dimensional bioprinted synthetic tissues and organ can be a clinical treatment option for damaged or diseased tissue repair and replacement. Conventional tissue engineering approaches have limited control over the regeneration of scaffold geometries and cell distribution. With the advancement of new biomaterials and additive manufacturing techniques, it is possible to develop physiologically relevant functional tissues or organs with living cells, bioactive molecules and growth factors within predefined complex 3D geometries. In this perspective, this review discusses how hydrogel-based bioinks can be used to mimic native tissue-like extracellular matrix environment, with optimal mechanical and structural integrity for patient-specific tissue regeneration, in reference to advanced bioprinting technologies to bioprint multitude of multicomponent bioinks. This review also summarizes various bioprinting techniques, the gelation and biodegradation mechanisms of hydrogel-based bioinks, the properties required for ideal bioink, challenges to design bioinks, as well as reviews the fabrication of 3D printed cardiac tissue, cartilages, brain-like tissue, bionic ear, and urinary system
Effect of structural isomerism in BODIPY based donor-acceptor co-polymers on their photovoltaic performance
No full textBorondipyrromethene or BODIPY can be incorporated into the polymer backbone through either the alpha (or 2,6) positions or the beta (3,5) positions and hence resulting in polymers exhibiting structural isomerism. In this work two pairs of such isomeric D-A polymers formed by copolymerization of BODIPY with benzodithiophene (P1 and P2) and fluorene (P3 and P4) separately are reported along with structure property correlation. Depending on the positions of attachment of the BODIPY unit in the isomeric polymers, the geometry of the polymer backbone is either coiled or linear which in turn affects physical properties such as thermal stability, solubility and absorption, electronic properties such as delocalization of molecular orbitals, HOMO-LUMO energy levels and band gap. Though the charge carrier mobility seems to remain unaffected due to the isomerism of the polymer backbone, the alpha connected polymers perform better than the beta connected polymers when used as electron acceptor along with P3HT in all polymer solar cells. This is also the first instance of application of BODIPY copolymers as electron acceptor in organic solar cells
Comprehensive amplification estimation of the Indo Gangetic Basin deep soil sites in the seismically active area
No full textSite amplification coefficients and acceleration design response spectra (ADRS) for the deep Indo-Gangetic Basin (IGB) have been proposed. Non-linear site response analysis is carried out at 275 deep shear wave velocity (V-S) profiles by selecting the input motion based on seismic hazard map for 10% probability of exceedence in 50 years. The spatial variation map of peak ground acceleration (PGA) and spectral acceleration (SA) at surface and various depths for the JOB are also presented. The bedrock PGA of 0.03-0.24 g increased to 0.1-0.97 g at surface and 0.05-0.35 g at a depth of 150 m. Maximum SA is observed between 0.08 s and 0.5 sec. The new site factors viz. F-a and F-v are derived for newly defined spectral period range. Further, ADRS is constructed which depends on PGA and seismic site class as per NEHRP. Proposed ADRS is compared with different deep basin studies and BIS:1893