Potentiometric and Blood Plasma Simulation Studies of Nickel(II) Complexes of Poly(amino)amido Pentadentate Ligands: Computer Aided Metal-Based Drug Design

The thermodynamic equilibria of nickel(II) with N,N′-di(aminoethylene)-2,6-pyridinedicarbonylamine (L1), Bis-(N,N-dimethylethyl)-2,6-pyridinedicarboxamide (L2), and N,N′-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (L3) have been studied at 25°C and an ionic strength of 0.15 mol dm−3 by glass electrode potentiometry. The protonation and formation constants added to blood plasma model predict that Cu(II) competes effectively against Ni(II), Zn(II), and Ca(II) for these ligands in vivo

Finding the way forward for forensic science in the US:a commentary on the PCAST report

A recent report by the US President’s Council of Advisors on Science and Technology (PCAST) [1] has made a number of recommendations for the future development of forensic science. Whereas we all agree that there is much need for change, we find that the PCAST report recommendations are founded on serious misunderstandings. We explain the traditional forensic paradigms of match and identification and the more recent foundation of the logical approach to evidence evaluation. This forms the groundwork for exposing many sources of confusion in the PCAST report. We explain how the notion of treating the scientist as a black box and the assignment of evidential weight through error rates is overly restrictive and misconceived. Our own view sees inferential logic, the development of calibrated knowledge and understanding of scientists as the core of the advance of the profession

In Silico Screening for Pesticide Candidates against the Desert Locust Schistocerca gregaria

Adipokinetic hormone (AKH) is one of the most important metabolic neuropeptides in insects, with actions similar to glucagon in vertebrates. AKH regulates carbohydrate and fat metabolism by mobilizing trehalose and diacylglycerol into circulation from glycogen and triacylglycerol stores, respectively, in the fat body. The short peptide (8 to 10 amino acids long) exerts its function by binding to a rhodopsin-like G protein-coupled receptor located in the cell membrane of the fat body. The AKH receptor (AKHR) is, thus, a potential target for the development of novel specific (peptide) mimetics to control pest insects, such as locusts, which are feared for their prolific breeding, swarm-forming behavior and voracious appetite. Previously, we proposed a model of the interaction between the three endogenous AKHs of the desert locust, Schistocerca gregaria, and the cognate AKHR (Jackson et al., Peer J. 7, e7514, 2019). In the current study we have performed in silico screening of two databases (NCI Open 2012 library and Zinc20) to identify compounds which may fit the endogenous Schgr-AKH-II binding site on the AKHR of S. gregaria. In all, 354 compounds were found to fit the binding site with glide scores < −8. Using the glide scores and binding energies, 7 docked compounds were selected for molecular dynamic simulation in a phosphatidylcholine membrane. Of these 7 compounds, 4 had binding energies which would allow them to compete with Schgr-AKH-II for the receptor binding site and so are proposed as agonistic ligand candidates. One of the ligands, ZINC000257251537, was tested in a homospecific in vivo biological assay and found to have significant antagonistic activity

Insights into the Activation of a Crustacean G Protein-Coupled Receptor: Evaluation of the Red Pigment-Concentrating Hormone Receptor of the Water Flea Daphnia pulex (Dappu-RPCH R)

The validation of a previously developed model of the interaction between the red pigment-concentrating hormone of Daphnia pulex and its cognate receptor (Jackson et al., IJBM 106, 969–978, 2018) was undertaken. Single amino acid replacements, noticeably an Ala scan, of the ligand, Dappu-RPCH, were docked to the receptor, and the binding energies calculated and compared to the one with Dappu-RPCH. As a second step, the same molecules were docked using molecular dynamics (MD) in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane. Changes in binding energy were compared to previous results on in vitro receptor activation (Marco et al., Sci. Rep. 7, 6851, 2017). Residue scanning and MD simulations both gave comparable results for binding energy. For most mutants, there was a good inverse correlation between in vitro activity and binding. There were, however, exceptions; for example: [Ala4]Dappu-RPCH bound as tightly as the cognate ligand but had little activity. This seeming discrepancy was explained when the MD data were analyzed in detail, showing that, although [Ala4]Dappu-RPCH had multiple interactions with the receptor accounting for the high binding energy, the interacting residues of the receptor were quite different to those of Dappu-RPCH. The MD calculations show clearly that the strong binding affinity of the ligand to the receptor is not sufficient for activation. Interaction of the binding of the ligand to two residues of the receptor, Ser 155 and Gln 237, is also essential. A comparison of our computational results with the experimental results of Marco et al. and comparison with the extensive data on GnRH supports the validity of our Dappu-RPCH R model

Ecological innovations in the Cambrian and the origins of the crown group phyla

One contribution of 16 to a discussion meeting issue 'Homology and convergence in nervous system evolution'

A response to “Likelihood ratio as weight of evidence: a closer look” by Lund and Iyer

Recently, Lund and Iyer (L&I) raised an argument regarding the use of likelihood ratios in court. In our view, their argument is based on a lack of understanding of the paradigm. L&I argue that the decision maker should not accept the expert’s likelihood ratio without further consideration. This is agreed by all parties. In normal practice, there is often considerable and proper exploration in court of the basis for any probabilistic statement. We conclude that L&I argue against a practice that does not exist and which no one advocates. Further we conclude that the most informative summary of evidential weight is the likelihood ratio. We state that this is the summary that should be presented to a court in every scientific assessment of evidential weight with supporting information about how it was constructed and on what it was based

Hydrogeologic Characterization of the Saline Aquifers, East Texas Basin- Implications to Nuclear Waste Storage in East Texas salt Domes

Groundwaters in the deep aquifers (Nacatoch to Travis Peak) range in salinity from 20,000 to over 200,000 mg/L. Based on their isotopic compositions, they were originally recharged as continental meteoric waters. Recharge probably occurred predominantly during the Cretaceous time; therefore, the waters are very old. Because the basin has not been uplifted, there are no extensive recharge or discharge zones. The flanks of domes and radial faults associated with domes may function as localized discharge points. Both the water chemistry and the hydraulic pressures for the aquifers suggest that the basin can be subdivided into two major aquifer systems: (1) the upper Cretaceous aquifers (Woodbine and shallower) which are hydrostatic and (2) the deep lower Cretaceous and deeper formations (Glen Rose, Travis Peak, and older units), which are slightly overpressured. The source of sodium and chloride in the saline waters is considered to be from salt dome dissolution. Most of the dissolution occurred during the Cretaceous. Chlorine-36 analyses suggest that dome solution is not presently occurring. Salinity cross sections across individual domes do not indicate that ongoing solution is an important process. The major chemical reactions in the saline aquifers are dome dissolution, albitization, and dedolomitization. Albitization and dedolomitization are important only in the deeper formations. The high Na concentrations in the deeper aquifer system result in the alteration of plagioclase to albite and the release of Ca into solution. The increase in Ca concentrations causes a shift in the calcite/dolomite equilibrium. The increase in Mg results from dissolution of dolomite.Bureau of Economic Geolog

Some inequalities for the Tutte polynomial

We prove that the Tutte polynomial of a coloopless paving matroid is convex along the portions of the line segments x+y=p lying in the positive quadrant. Every coloopless paving matroids is in the class of matroids which contain two disjoint bases or whose ground set is the union of two bases of M*. For this latter class we give a proof that T_M(a,a) <= max {T_M(2a,0), T_M(0,2a)} for a >= 2. We conjecture that T_M(1,1) <= max {T_M(2,0), T_M(0,2)} for the same class of matroids. We also prove this conjecture for some families of graphs and matroids.Comment: 17 page

Quantum Vacuum Contribution to the Momentum of the Dielectric Media

Momentum transfer between matter and electromagnetic field is analyzed. The related equations of motion and conservation laws are derived using relativistic formalism. Their correspondence to various, at first sight self-contradicting, experimental data (the so called Abraham-Minkowski controversy) is demonstrated. A new, Casimir like, quantum phenomenon is predicted: contribution of vacuum fluctuations to the motion of dielectric liquids in crossed electric and magnetic fields. Velocities about $50nm/s$ can be expected due to the contribution of high frequency vacuum modes

Gamma Ray Lines from a Universal Extra Dimension

Indirect Dark Matter searches are based on the observation of secondary particles produced by the annihilation or decay of Dark Matter. Among them, gamma-rays are perhaps the most promising messengers, as they do not suffer deflection or absorption on Galactic scales, so their observation would directly reveal the position and the energy spectrum of the emitting source. Here, we study the detailed gamma-ray energy spectrum of Kaluza--Klein Dark Matter in a theory with 5 Universal Extra Dimensions. We focus in particular on the two body annihilation of Dark Matter particles into a photon and another particle, which produces monochromatic photons, resulting in a line in the energy spectrum of gamma rays. Previous calculations in the context of the five dimensional UED model have computed the line signal from annihilations into \gamma \gamma, but we extend these results to include \gamma Z and \gamma H final states. We find that these spectral lines are subdominant compared to the predicted \gamma \gamma signal, but they would be important as follow-up signals in the event of the observation of the \gamma \gamma line, in order to distinguish the 5d UED model from other theoretical scenarios.Comment: 21 pages, 6 figure