Combined pharmacophore-guided 3D-QSAR,molecular docking,and virtual screening on bis-benzimidazoles and ter-benzimidazoles as DNA–topoisomerase I poisons

Structural Chemistry - Certain DNA minor groove binders, especially bis-benzimdazole containing compounds, such as Hoechst 33258 and its derivatives, act as potent topoisomerase I inhibitors. The...     

A Solid‐State Protein Junction Serves as a Bias‐Induced Current Switch

A sample‐type protein monolayer, that can be a stepping stone to practical devices, can behave as an electrically driven switch. This feat is achieved using a redox protein, cytochrome C (CytC), with its heme shielded from direct contact with the solid‐state electrodes. Ab initio DFT calculations, carried out on the CytC–Au structure, show that the coupling of the heme, the origin of the protein frontier orbitals, to the electrodes is sufficiently weak to prevent Fermi level pinning. Thus, external bias can bring these orbitals in and out of resonance with the electrode. Using a cytochrome C mutant for direct S?Au bonding, approximately 80 % of the Au–CytC–Au junctions show at greater than 0.5 V bias a clear conductance peak, consistent with resonant tunneling. The on–off change persists up to room temperature, demonstrating reversible, bias‐controlled switching of a protein ensemble, which, with its built‐in redundancy, provides a realistic path to protein‐based bioelectronics.     

Synergism of the Bacillus thuringiensis Cry1, Cry2, and Vip3 Proteins in Spodoptera frugiperda Control

The polyphagous caterpillar, Spodoptera frugiperda, has been controlled with either chemical insecticides or transgenic plants such as Bt maize that expresses the cry and/or vip genes of the Bacillus thuringiensis (Bt) bacterium. Despite the efficiency of Bt toxins in lepidopteran control, populations resistant to Bt plants have emerged in different locations around the world. Thus, understanding how combined proteins interact against pests can assist resistance control and management. This work demonstrated the toxicity of Cry1Ab, Cry1Ac, Cry1Ca, Cry1Ea, Cry2Aa, Cry2Ab, Vip3Aa, and Vip3Ca in single and combined assays against S. frugiperda neonatal larvae. All protein mixtures had synergistic action in the control of the larvae. The Vip3Aa + Cry1Ab mixture had the highest toxicity, sequentially followed by Vip3Aa + Cry2Ab, Cry1Ab + Cry2Ab + Vip3Aa, Cry1Ea + Cry1Ca, Cry1Ab + Cry2Ab, Vip3Ca + Cry1Ea, and Vip3Ca + Cry1Ca. Cry1Ab, Cry1Ac, Cry2Ab, and Vip3Aa bound to more than one site on the brush border membrane vesicles (BBMV) of S. frugiperda. The Cry1Ab and Cry1Ac proteins share binding site, while Cry1Ab does not share binding site with the Cry2Aa and Cry2Ab proteins. The Vip3Aa protein does not share receptors with the tested Cry1 and Cry2. The results suggest that combination these tested proteins may increase toxicity against S. frugiperda neonates.

     

Testing noncommutative spacetimes and violations of the Pauli Exclusion Principle through underground experiments

We propose to deploy limits that arise from different tests of the Pauli Exclusion Principle: i) to provide theories of quantum gravity with experimental guidance; ii) to distinguish, among the plethora of possible models, the ones that are already ruled out by current data; iii) to direct future attempts to be in accordance with experimental constraints. We first review experimental bounds on nuclear processes forbidden by the Pauli Exclusion Principle,which have been derived by several experimental collaborations making use of various detector materials. Distinct features of the experimental devices entail sensitivities on the constraints hitherto achieved that may differ from one another by several orders of magnitude. We show that with choices of these limits, well-known examples of flat noncommutative space-time instantiations of quantum gravity can be heavily constrained, and eventually ruled out.We devote particular attention to the analysis of the κ-Minkowski and θ-Minkowski noncommutative spacetimes.These are deeply connected to some scenarios in string theory, loop quantum gravity, and noncommutative geometry.We emphasize that the severe constraints on these quantum spacetimes, although they cannot rule out theories of top-down quantum gravity to which they are connected in various ways, provide a powerful limitation for those models. Focus on this will be necessary in the future.     

Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies

In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, p = 0.03 and p= 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, p = 0.006 and p = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.     

Self-propelled particle model for cell-sorting phenomena

A self-propelled particle model is introduced to study cell sorting occurring in some living organisms. This allows us to evaluate the influence of intrinsic cell motility separately from differential adhesion with fluctuations, a mechanism previously shown to be sufficient to explain a variety of cell rearrangement processes. We find that the tendency of cells to actively follow their neighbors greatly reduces segregation time scales. A finite-size analysis of the sorting process reveals clear algebraic growth laws as in physical phase-ordering processes, albeit with unusual scaling exponents.     

Effect of superficially applied ZrO2 inhibitor on the high temperature corrosion performance of some Fe-, Co- and Ni-base superalloys

High temperature corrosion is an acute form of corrosion occurring at elevated temperature in the presence of an oxidizing gas and is associated with a thin electrolytic deposit (salt or ash) on alloy. Inhibitors and fuel additives have been used with varying success to combat oil ash corrosion. In this paper, the effect of an oxide additive namely ZrO₂ on the hot corrosion behaviour of some superalloys, viz. Superfer 800H (alloy A), Superco 605 (alloy B) and Superni 75 (alloy C) has been investigated in an Na₂SO₄-60%V₂O₅ environment at 900 °C for 50 cycles. Each cycle consisted of 1 h heating in a Silicon Carbide Tube furnace followed by 20 min cooling in ambient air. Weight change measurements after each cycle were taken by an electronic balance having an accuracy of 0.01 mg. XRD, SEM and EPMA analyses of the exposed specimens were carried out to characterize the oxide scales. In the Na₂SO₄-60%V₂O₅ environment, the corrosion rate for the Co-base alloy was found to be highest, whereas that for the Ni-base Superni 75 a lowest. Whereas, with ZrO₂ superficial coating, the overall weight gains got reduced for the alloys B and C, however the inhibitor was marginally effective in the alloy A. A thick scale was observed in the latter case, which was rich in Cr, Ni, Fe and V. Absence of protective continuous chromia layer and presence of less protective NiO was probably the main reason for more corrosion rate in this case.     

Scheduling of a Two-machine Flowshop with Processing Time Linearly Dependent on Job Waiting-time

This paper deals with the problem of finding the minimum finish-time schedule in a two-machine flowshop, where the processing times of jobs are linearly dependent on the job waiting-times. The problem is shown to be NP-hard. A heuristic algorithm is presented, and the worst-case bounds are derived for the different variations of the algorithm.