A study on monotone self-dual Boolean functions

This paper shows that monotone self-dual Boolean functions in irredundant disjuntive normal form (IDNF) do not have more variables than disjuncts. Monotone self-dual Boolean functions in IDNF with the same number of variables and disjuncts are examined. An algorithm is proposed to test whether a monotone Boolean function in IDNF with n variables and n disjuncts is self-dual. The runtime of the algorithm is O(n³).     

Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes

Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB inhibitor, and P22077 as a USP7 inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy. A striking accumulation of polyubiquitylated proteins was observed after both selective and general inhibition of cellular DUB activity without direct impairment of proteasomal proteolysis. The repertoire of ubiquitylated substrates was analyzed by tandem mass spectrometry, identifying distinct subsets for general or specific inhibition of DUBs. This enabled identification of previously unknown functional links between USP7 and enzymes involved in DNA repair.     

Generalized Lucas polynomials and relationships between the Fibonacci polynomials and Lucas polynomials

In this article, we find elements of the Lucas polynomials by using two matrices. We extend the study to the n-step Lucas polynomials. Then the Lucas polynomials and their relationship are generalized in the paper. Furthermore, we give relationships between the Fibonacci polynomials and the Lucas polynomials.     

Direct flow injection profiling of acyl glycerols from food products using isopropanol as solvent

This work proposes a novel method for the direct flow injection profiling of acylglycerols in edible oils and fats without preliminary extraction and consequent reconstitution in the injection solvent. The work exploits the outstanding performance of high‐resolution mass spectrometry to target unique elemental compositions even in the most complex matrices. The performance of isopropanol as the unique solvent for both the solubilization and analysis of acylglycerols was investigated in comparison with other classical methods involving preliminary extractions, sample recovery, and analysis. The calibrations of two triglyceride standards (triolein and trilinolenin) were successfully performed in presence and absence of oil matrix. As final application, the effects on the acylglycerol fraction of a heat treatment on three different fat samples (extra virgin olive oil, lard oil, and fat from dry cured ham—speck) were monitored. The proposed method is therefore suitable for a rapid evaluation of acylglycerol fractions in food lipid samples.     

Quantum mechanical/molecular mechanical studies on spectral tuning mechanisms of visual pigments and other photoactive proteins

The protein environments surrounding the retinal tune electronic absorption maximum from 350 to 630 nm. Hybrid quantum mechanical/molecular mechanical (QM/MM) methods can be used in calculating excitation energies of retinal in its native protein environments and in studying the molecular basis of spectral tuning. We hereby review recent QM/MM results on the phototransduction of bovine rhodopsin, bacteriorhodopsin, sensory rhodopsin II, nonretinal photoactive yellow protein and their mutants.     

Weighted Hardy and Rellich type inequalities on Riemannian manifolds

In this paper we present new results on two‐weight Hardy, Hardy–Poincaré and Rellich type inequalities with remainder terms on a complete noncompact Riemannian Manifold M. The method we use is flexible enough to obtain more weighted Hardy type inequalities. Our results improve and include many previously known results as special cases.     

Common system setup for the entire catalytic cycle of cytochrome P450(cam) in quantum mechanical/molecular mechanical studies

We describe a system setup that is applicable to all species in the catalytic cycle of cytochrome P450(cam). The chosen procedure starts from the X-ray coordinates of the ferrous dioxygen complex and follows a protocol that includes the careful assignment of protonation states, comparison between different conceivable hydration schemes, and system preparation through a series of classical minimizations and molecular dynamics (MD) simulations. The resulting setup was validated by quantum mechanical/molecular mechanical (QM/MM) calculations on the resting state, the pentacoordinated ferric and ferrous complexes, Compound I, the transition state and hydroxo intermediate of the C--H hydroxylation reaction, and the product complex. The present QM/MM results are generally consistent with those obtained previously with individual setups. Concerning hydration, we find that saturating the protein interior with water is detrimental and leads to higher structural flexibility and catalytically inefficient active-site geometries. The MD simulations favor a low water density around Asp251 that facilitates side chain rotation of protonated Asp251 during the conversion of Compound 0 to Compound I. The QM/MM results for the two preferred hydration schemes (labeled SE-1 and SE-4) are similar, indicating that slight differences in the solvation close to the active site are not critical as long as camphor and the crystallographic water molecules preserve their positions in the experimental X-ray structures.     

What is the active species of cytochrome P450 during camphor hydroxylation? QM/MM studies of different electronic states of compound I and of reduced and oxidized iron-oxo intermediates

We have investigated C-H hydroxylation of camphor by Compound I (Cpd I) of cytochrome P450cam in different electronic states and by its one-electron reduced and oxidized forms, using QM/MM calculations in the native protein/solvent environment. Cpd I species with five unpaired electrons (pentaradicaloids) are ca. 12 kcal/mol higher in energy than the ground state Cpd I species with three unpaired electrons (triradicaloids). The H-abstraction transition states of pentaradicaloids lie ca. 21 (9) kcal/mol above the triradicaloid (pentaradicaloid) reactants. Hydroxylation via pentaradicaloids is thus facile provided that they can react before relaxing to the ground-state triradicaloids. Excited states of Cpd I with an Fe(V)-oxo moiety lie more than 20 kcal/mol above the triradicaloid ground state in single-point gas-phase calculations, but these electronic configurations are not stable upon including the point-charge protein environment which causes SCF convergence to the triradicaloid ground state. One-electron reduced species (Cpd II) show sluggish reactivity compared with Cpd I in agreement with experimental model studies. One-electron oxidized species are more reactive than Cpd I but seem too high in energy to be accessible. The barriers to hydrogen abstraction for the various forms of Cpd I are generally not affected much by the chosen protonation states of the Asp297 and His355 residues near the propionate side chains of the heme or by the appearance of radical character at Asp297, His355, or the propionates.     

Feasibility of post-gadolinium three-dimensional gradient-echo sequence to evaluate the pulmonary arterial vasculature

Purpose

To determine the feasibility of post-gadolinium three-dimensional gradient-echo (3D-GE) sequence for the evaluation of the pulmonary arterial vasculature in patients with suspected pulmonary embolism (PE) and in patients with a variety of other disease processes.

Materials and Methods

Twenty-six consecutive patients (18 females, 8 males; mean age±S.D., 46.6±21.1 years) who underwent chest magnetic resonance imaging (MRI) including post-gadolinium 3D-GE sequence for the evaluation of PE (Group A, n=13) and a variety of other disease processes (Group B, n=13) were included in the study. Post-gadolinium 3D-GE MR sequences were retrospectively, independently and blindly evaluated by two reviewers for the image quality of pulmonary arterial vasculature, and findings of PE and other disease processes. Clinical and imaging follow-up data for all patients were obtained. Interobserver agreement was calculated by kappa statistics.

Results

All central and lobar pulmonary arteries, 71.4–89.6% of segmental arteries and 46.7–52.7% of subsegmental arterial units in both groups were visualized with sufficient diagnostic image quality on post-gadolinium 3D-GE sequences. PE involving lobar and segmental arteries was diagnosed in two patients in each group. Other disease processes including pneumonia, lung nodules, superior vena cava stenosis, lung metastases, chronic lymphocytic leukemia and aortic aneurysm were detected in 10 of 26 patients. There was good to excellent interobserver agreement (0.73 to 1.00) for all findings.

Conclusion

Post-gadolinium 3D-GE sequence may be an alternative technique for the visualization of central, lobar and segmental arteries, and may diagnose PE and other pathologies involving the chest in different patient populations.