Developing novel activity-based fluorescent probes that target different classes of proteases

In this article, we report the design and synthesis of a group of novel activity-based probes that target different protease sub-classes based on their substrate specificities, rather than their enzymatic mechanisms. The feasibility of our approach has been demonstrated by using representative members of the different protease sub-classes.     

Production of Siderophores by an Apple Root-Associated Streptomyces ciscaucasicus Strain GS2 Using Chemical and Biological OSMAC Approaches

Apple Replant Disease (ARD) is a significant problem in apple orchards that causes root tissue damage, stunted plant growth, and decline in fruit quality, size, and overall yield. Dysbiosis of apple root-associated microbiome and selective richness of Streptomyces species in the rhizosphere typically concurs root impairment associated with ARD. However, possible roles of Streptomyces secondary metabolites within these observations remain unstudied. Therefore, we employed the One Strain Many Compounds (OSMAC) approach coupled to high-performance liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMSⁿ) to evaluate the chemical ecology of an apple root-associated Streptomyces ciscaucasicus strain GS2, temporally over 14 days. The chemical OSMAC approach comprised cultivation media alterations using six different media compositions, which led to the biosynthesis of the iron-chelated siderophores, ferrioxamines. The biological OSMAC approach was concomitantly applied by dual-culture cultivation for microorganismal interactions with an endophytic Streptomyces pulveraceus strain ES16 and the pathogen Cylindrocarpon olidum. This led to the modulation of ferrioxamines produced and further triggered biosynthesis of the unchelated siderophores, desferrioxamines. The structures of the compounds were elucidated using HRMSⁿ and by comparison with the literature. We evaluated the dynamics of siderophore production under the combined influence of chemical and biological OSMAC triggers, temporally over 3, 7, and 14 days, to discern the strain’s siderophore-mediated chemical ecology. We discuss our results based on the plausible chemical implications of S. ciscaucasicus strain GS2 in the rhizosphere.     

Small-angle neutron scattering studies on water soluble complexes of poly(ethylene glycol)-based cationic random copolymer and SDS

The interaction of cationic random copolymers of methoxy poly(ethylene glycol) monomethacrylate and (3-(methacryloylamino)propyl) trimethylammonium chloride with oppositely charged surfactant, sodium dodecyl sulphate, and the influence of surfactant association on the polymer conformation have been investigated by small-angle neutron scattering. SANS data showed a positive indication of the formation of RCPSDS complexes. Even though the complete structure of the polyion complexes could not be ascertained, the results obtained give us the information on the local structure in these polymer-surfactant systems. The data were analysed using the log-normal distribution of the polydispersed spherical aggregate model for the local structure in these complexes. For all the systems the median radius and the polydispersity were found to be in the range of 20 ± 2 Å and 0.6 ± 0.05, respectively.     

Rh(III)-catalyzed directed C-H olefination using an oxidizing directing group: mild, efficient, and versatile

An efficient Rh(III)-catalyzed oxidative olefination by directed C-H bond activation of N-methoxybenzamides is reported. In this mild, practical, selective, and high-yielding process, the N-O bond acts as an internal oxidant. In addition, simply changing the substituent of the directing/oxidizing group results in the selective formation of valuable tetrahydroisoquinolinone products.     

On data complexity of distinguishing attacks versus message recovery attacks on stream ciphers

We revisit the different approaches used in the literature to estimate the data complexity of distinguishing attacks on stream ciphers and analyze their inter-relationships. In the process, we formally argue which approach is applicable (or not applicable) in what scenario. To our knowledge, this is the first kind of such an exposition. We also perform a rigorous statistical analysis of the message recovery attack that exploits a distinguisher and show that in practice there is a significant gap between the data complexities of a message recovery attack and the underlying distinguishing attack. This gap is not necessarily determined by a constant factor as a function of the false positive and negative rate, as one would expect. Rather this gap is also a function of the number of samples of the distinguishing attack. We perform a case study on RC4 stream cipher to demonstrate that the typical complexities for message recovery attack inferred in the literature are but under-estimates and the actual estimates are quite larger.     

Effect of loop orientation on quadruplex-TMPyP4 interaction

G-quadruplexes are believed to be potential targets for therapeutic intervention and this has resulted in designing of various quadruplex interacting ligands. Moreover, reports about existence of quadruplex forming sequences across the genome have propelled greater interest in understanding their interaction with small molecules. An intramolecular quadruplex sequence can adopt different conformations, owing to different orientation of loops in the structure. The differences in the loop orientation can affect their molecular recognition. Herein, we have studied the interaction of 5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H, 23H-porphine (TMPyP4), a well-known G quadruplex binding ligand with three DNA quadruplexes differing in loop orientations. Results obtained from UV, ITC, and SPR studies have coherently revealed that the TMPyP4 molecule shows preferential binding to parallel G-quadruplex ( c-myc and c-kit) over its antiparallel counterpart (human telomeric). The binding affinity for parallel quadruplex was (10(7)) 1 order of magnitude higher than that for antiparallel DNA quadruplex (10 ). The study shows two binding modes, stronger binding (10(7)) of TMPyP4 involving end stacking and a weaker external binding (10 ), while TMPyP4 shows only one binding mode with duplex with a binding affinity of the order of 10(6). Overall, the study emphasizes that differences in the loop orientation give rise to different conformations of quadruplex, which in turn govern its binding to small molecules, and thereby play a pivotal role in molecular recognition.     

Asynchronous cellular automata and pattern classification

This article designs an efficient two‐class pattern classifier utilizing asynchronous cellular automata (ACAs). The two‐state three‐neighborhood one‐dimensional ACAs that converge to fixed points from arbitrary seeds are used here for pattern classification. To design the classifier, (1) we first identify a set of ACAs that always converge to fixed points from any seeds, (2) each ACA should have at least two but not huge number of fixed point attractors, and (3) the convergence time of these ACAs are not to be exponential. To address the second issue, we propose a graph, coined as fixed point graph of an ACA that facilitates in counting the fixed points. We further perform an experimental study to estimate the convergence time of ACAs, and find there are some convergent ACAs which demand exponential convergence time. Finally, we identify there are 73 (out of 256) ACAs which can be effective candidates as pattern classifier. We use each of the candidate ACAs on some standard datasets, and observe the effectiveness of each ACAs as pattern classifier. It is observed that the proposed classifier is very competitive and performs reliably better than many standard existing classifier algorithms. © 2016 Wiley Periodicals, Inc. Complexity 21: 370–386, 2016     

An examination of the flow induced by the motion of many buoyant bubbles

The results of direct numerical simulations of the motion of many three-dimensional buoyant bubbles in periodic domains are examined. The bubble motion is computed by solving the full Navier-Stokes equations by a parallelized finite difference/front tracking method that allows a fully deformable interface between the bubbles and the ambient fluid and the inclusion of surface tension. The governing parameters are selected such that the average rise Reynolds number is about 25. Two cases are examined. In one, the bubbles are nearly spherical; in the other, the bubbles rise with an ellipsoidal shape. The ellipsoidal bubbles show a much larger fluctuation velocity and by visualizing the flow field it is possible to show that the difference is due to larger vorticity generation and stronger interactions of the deformable bubbles. The focus here is on the early stage of the flow, when both the spherical and the deformable bubbles are nearly uniformly distributed.