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You Cannot Have Your Synergy and Efficacy Too
No full textSynergistic drugs are preferred in combination therapies for many diseases, including viral infections and cancers. Maximizing synergy, however, may come at the cost of efficacy. This synergy-efficacy trade-off appears to be widely prevalent and independent of the specific drug interactions yielding synergy. We present examples of the trade-off in drug combinations used in hepatitis C, HIV, and cancer therapies and believe that screens for optimal drug combinations that presently seek to maximize synergy may be improved by considering the trade-off
Predicting gas phase entropy of select hydrocarbon classes through specific information-theoretical molecular descriptors
No full textThe usefulness of five specific information-theoretical molecular descriptors was investigated for predicting the gas phase entropy of selected classes of acyclic and cyclic compounds. Among them, total information on atomic number (TIZ), graph vertex complexity (H-V) and total information on bonds (TIBAT), considered together showed the best correlation along with a low standard deviation (r(2) = 0.97, s = 21.14) with gas phase entropy values of 130 compounds. The multiple regression equation treating these three indices as independent variables was statistically highly significant which was evident from the F-statistics. In particular, very small difference between r(2) and r(2)-pred values indicates that the regression model is not overfitted and is, therefore, suitable for prediction purposes. When truly used as a training set to predict (from regression equation) 40 additional compounds we get a very high correlation (r(2) = 0.975), which remains almost identical (r(2) = 0.97) for the combined data set of 170 compounds. The three indices appear to be useful descriptors producing correlation that remains stable with the change in the size of the data set. Also, the information-theoretical measures appear to capture an additive-cum-constitutive nature of gas phase entropy yielding an acceptable statistical fit
Concurrent Subthermionic and Strong Thermionic Transport in Inkjet-Printed Indium Zinc Oxide/Silver Hybrid-Channel Field-Effect Transistors
No full textSubthreshold slope of field-effect transistors (FETs) less than the fundamental Boltzmann limit (60 mV dec(-1) at 300 K) is demonstrated either using band-to-band tunneling or negative capacitance (NC) ferroelectric-gate transistors. However, it is difficult to replicate both of these strategies in solution-processed/printed FETs. Nonetheless, it is shown that the use of a metal-insulator-metal-semiconductor architecture alongside electrolyte gating can simultaneously create highly reproducible static negative capacitance behavior in printed FETs, resulting in subthermionic transport for over four decades of drain currents with a subthreshold slope as low as 16 mV dec(-1), and thereafter a strong thermionic transport regime, characterized by an unprecedented On-current of 195 mu A mu m(-1), a transconductance of 215 mu S mu m, and a metal-like On-state resistance of only 96 omega. The present device architecture is analogous to typical metal oxide semiconductor field-effect transistor (MOSFET) geometry with printed amorphous indium zinc oxide (a-IZO) as the semiconductor material, besides an additional metal layer on top of the a-IZO channel that reduces the actual semiconducting channel dimension to the thickness of the printed a-IZO layer. While the steep slope subthermionic transport regime can be utilized at wearable sensor interfaces, the high On-currents/channel conductance can be used in optoelectronic applications, high-current switches, and amplifiers
Specialized structural and functional roles of residues selectively conserved in subfamilies of the pleckstrin homology domain family
No full textHomologous domains embedded in multidomain proteins of different domain architectures (DA) may exhibit subtle, but important, differences in their structure and function. Here, we consider two multidomain proteins, Arf nucleotide binding site opener (ARNO) and G protein-coupled receptor kinase 2 (GRK2), which have very different DAs, but both contain pleckstrin homology (PH) domains. We analyzed the roles of residues selectively conserved in these subfamilies of PH domains from ARNO and GRK2 proteins. DA-specific residues in PH domain are found to contribute to structural and functional specialization of ARNO and GRK2 in terms of (a) specific intra- and interprotein interactions; (b) specificity for phospholipids; and (c) participation in conformational excursions, leading to various functional forms. Our approach can also be applied to subfamilies of other protein families to identify subfamily-specific residues and their specialized roles
Tuning molecular fluctuation to boost the conductance in DNA based molecular wires
No full textInherent molecular fluctuations are known to have a significant influence on the charge transport properties of biomolecules like DNA, PNA and proteins. In this work, we show ways to control these fluctuations and further demonstrate their use to enhance the conductance of two widely studied molecular wires, namely dsDNA (DNA) and G4 Quadruplex (G4-Quad). We quantify the molecular fluctuation in terms of the root mean square deviation (RMSD) of the molecule. In the case of DNA, we use temperature to control the fluctuations, while in the case of G4-Quad the fluctuations are tuned by the ions inside the pore. The electronic coupling between the bases of dsDNA and G4-Quad, which measures the conductance of these molecular wires, shows a non-monotonic behaviour with the increase in fluctuation. We find values of fluctuation which give rise to maximum electronic coupling and hence high conductivity for both the cases. In the case of DNA, these optimal fluctuations (similar to 2.5 angstrom) are achieved at a temperature of 210 K, which gives rise to an electronic coupling of 0.135 eV between the DNA bases. The optimal fluctuations in G4-Quad are achieved (similar to 7 angstrom) in a 4 base pair long system with 2 Na+ ions inside the pore, giving rise to an electronic coupling of 0.09 eV
Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative (vol 40, pg 4855, 2011)
No full textDuring the course of revising the manuscript, the authors inadvertently selected an incorrect image for Fig. 9c (1 + Fe2+). This image was mistakenly duplicated from Fig. 9e during preparation of the figures. The correction to the image in Fig. 9c does not affect the conclusions of the paper. The corrected Fig. 9 is shown here. The text, the figure legends, and the conclusions of this article are not affected by this correction. The authors apologize for any inconvenience that these errors in final figure revision/preparation may have caused. (Figure Presented). The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers
Gradient crystallinity and its influence on the poly(vinylidene fluoride)/poly(methyl methacrylate) membrane-derived by immersion precipitation method
No full textHerein, phase inversion poly(vinylidene fluoride)/poly(methyl methacrylate) (PVDF/PMMA) microporous membranes were prepared at various PMMA concentration by immersion precipitation method. Increment in the PMMA concentration has a significant influence in the PVDF membrane crystallinity, which is studied by differential scanning calorimeter, X-ray diffractometer, and small-angle X-ray scattering analyses. Properties such as membrane bulk structure, porosity, hydrophilicity, mechanical stability, and water flux vary in terms of PMMA concentration. Porosity is increased, and tensile strength decreased when PMMA concentration is beyond 30 wt %. Thermodynamic instability during the liquid to solid phase separation and variation in the crystallinity has an intense effect on these membrane properties. Then, 70/30 blend membrane selected as optimum composition owing to the high porosity and pure water flux compared to other compositions. This membrane is modified with a composite filler derived from the graphene oxide and titanate crosslinked by chitosan. The antibacterial, antifouling, and bovine serum albumin separation studies reveal that the developed nanocomposite membrane is a potential candidate for the separation application
Roles of the troponin isoforms during indirect flight muscle development in Drosophila (vol 93, pg 379, 2014)
No full textCathodoluminescence enhancement and quenching in type-I van der Waals heterostructures: Cleanliness of the interfaces and defect creation
No full textLayered materials, such as transition metal dichalcogenides, can be combined at will in van der Waals heterostructures and lead to a variety of new phenomena. To better understand the coupling between layers and the variation of electronic and optical properties, noninvasive techniques with the best possible spatial resolution are needed. Here we show that due to an enhanced interaction cross section with electrons in a type-I van der Waals heterostructure, made of single-layer molybdenum disulfide and thin boron nitride, cathodoluminescence is strongly enhanced. It can be mapped with a spatial resolution far exceeding what can be achieved in more commonly used photoluminescence experiments, thereby providing invaluable insights into the optoelectronic properties at the nanoscale. We demonstrate that the technique is noninvasive, i.e., it does not induce any defect, only if the interface between boron nitride and the molybdenum disulfide layer is pristine. In the presence of trapped species, structural defects are locally induced by the electron beam in the layer. Such defects quench the luminescence and present clear Raman signatures. We show that optimizing the heterostructure preparation techniques can lead to extended areas with clean interfaces that lead to a more homogeneous cathodoluminescence signal
Femtosecond laser fabrication of silver nanostructures on glass for surface enhanced Raman spectroscopy
No full textWe report on an optimized fabrication protocol for obtaining silver nanoparticles on fused silica substrates via laser photoreduction of a silver salt solution. We find that multiple scans of the laser over the surface leads to a more uniform coverage of densely packed silver nanoparticles of approximately 50 nm diameter on the fused silica surface. Our substrates yield Raman enhancement factors of the order of 1011 of the signal detected from crystal violet. We use a theoretical model based on scanning electron microscope (SEM) images of our substrates to explain our experimental results. We also demonstrate how our technique can be extended to embedding silver nanoparticles in buried microfluidic channels in glass. The in situ laser inscription of silver nanoparticles on a laser machined, sub-surface, microfluidic channel wall within bulk glass paves the way for developing 3D, monolithic, fused silica surface enhance Raman spectroscopy (SERS) microfluidic sensing devices