Achieving global perfect homeostasis through transporter regulation

Nutrient homeostasis—the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments—is essential to the survival of most organisms. Transcriptional regulation of plasma membrane transporters by internal nutrient concentrations is typically assumed to be the main mechanism by which homeostasis is achieved. While this mechanism is homeostatic we show that it does not achieve global perfect homeostasis—a condition where internal nutrient concentrations are completely independent of external nutrient concentrations for all external nutrient concentrations. We show that the criterion for global perfect homeostasis is that transporter levels must be inversely proportional to net nutrient flux into the cell and that downregulation of active transporters (activity-dependent regulation) is a simple and biologically plausible mechanism that meets this criterion. Activity-dependent transporter regulation creates a trade-off between robustness and efficiency, i.e., the system's ability to withstand perturbation in external nutrients and the transporter production rate needed to maintain homeostasis. Additionally, we show that a system that utilizes both activity-dependent transporter downregulation and regulation of transporter synthesis by internal nutrient levels can create a system that mitigates the shortcomings of each of the individual mechanisms. This analysis highlights the utility of activity-dependent regulation in achieving homeostasis and calls for a re-examination of the mechanisms of regulation of other homeostatic systems

Effect of triphosphate modifications in 2′-deoxynucleoside 5′-triphosphates on their specificity towards various DNA polymerases

AbstractSome natural and glycon-modified dNTPs with β,γ-pyrophosphate substitution at the triphosphate residue were synthesized and studied to evaluate the effect of these modifications on substrate properties of dNTPs in DNA synthesis catalyzed by human placental DNA polymerases α and β, avian myeloblastosis virus reverse transcriptase, and calf thymus terminal deoxynucleotidyl transferase. Reverse transcriptase proved to be the enzyme least specific to such modifications; the substrate activity of β,γ-methylenediphosphonate substituted dTTP and 3′-azido-3′-deoxy-dTTP decreased in the following order: CF2=CHF>CBr2>CFMe≫CH2. This order is individual for each DNA polymerase. It is interesting to mention that β,γ-CBr2 substituted dTTP is neither a substrate nor an inhibitor of DNA polymerase β. This specificity distinguishes DNA polymerase β from other DNA polymerases studied

Synchronous Multiple Primary Lung Cancer: A Case Report

The incidence of multiple primary malignancies has increased dramatically in recent decades. Herein we report synchronous multiple primary lung cancer (SMPLC) in a 52-year-old male patient. It is advisable to consider SMPLC as a local pathology and to perform radical surgical treatment, which contributes to a favorable outcome

Improvement of firebrand tracking and detection software

Burning and glowing firebrands generated by wildland and urban fires may lead to the initiation of spot fnes and the ignition of structures. One of the ways to obtain this infonnation is to process tliennal video files. Earlier, a number of algorithms were developed for the analysis of the characteristics of fu'ebrands under field conditions. However, they had certain disadvantages. In this regard, this work is devoted to the development of new algorithms and their testing

iPatient in medical information systems and future of internet of health

The results of Study "iHealthCare Optimization", provided by Dell EMC External Research and Academic Alliances, are presented. Big Data analytics of Medical information system qMS records was implemented using cluster analysis in Python. Software for cluster analysis was created by Andrey Mazelis (Vladivostok State University of Economics and Service). There are two directions of cluster analysis: Series treatment (number of investigation procedures for each patient) and Series time (waiting time for investigation procedures for each patient). Two models of patients management (Model A and Model B) were found, that can be used for better planning of care management. Models approach provides the new capability to implement Health Care Standard in mode aaS, using feedback after Big Data analytics. Around 80-90% of patients with Essential hypertension can get treatment in Day Hospital without hospitalization

Structure of ternary additive hard-sphere fluid mixtures

Monte Carlo simulations on the structural properties of ternary fluid mixtures of additive hard spheres are reported. The results are compared with those obtained from a recent analytical approximation [S. B. Yuste, A. Santos, and M. Lopez de Haro, J. Chem. Phys. 108, 3683 (1998)] to the radial distribution functions of hard-sphere mixtures and with the results derived from the solution of the Ornstein-Zernike integral equation with both the Martynov-Sarkisov and the Percus-Yevick closures. Very good agreement between the results of the first two approaches and simulation is observed, with a noticeable improvement over the Percus-Yevick predictions especially near contact.Comment: 11 pages, including 8 figures; A minor change; accepted for publication in PR

Low-Symmetry Phthalocyanines Bearing Carboxy-Groups

The synthesis and characterization of A3B-type phthalocyanines, ZnPc1–4, bearing bulky 2,6-diisopropylphenoxy-groups or chlorine atoms on isoindoline units “A” and either one or two carboxylic anchors on isoindoline unit “B” are reported. A comparison of molecular modelling with the conventional time dependent—density functional theory (TD-DFT) approach and its simplified sTD-DFT approximation provides further evidence that the latter method accurately reproduces the key trends in the spectral properties, providing colossal savings in computer time for quite large molecules. This demonstrates that it is a valuable tool for guiding the rational design of new phthalocyanines for practical applications

Methodological Survey of Simplified TD-DFT Methods for Fast and Accurate Interpretation of UV−Vis−NIR Spectra of Phthalocyanines

A methodological survey of density functional theory (DFT) methods for the prediction of UV−visible (vis)−near-infrared (NIR) spectra of phthalocyanines is reported. Four methods, namely, full time-dependent (TD)-DFT and its Tamm−Dancoff approximation (TDA), together with their simplified modifications (sTD-DFT and sTDA, respectively), were tested by using the examples of unsubstituted and alkoxy-substituted metal-free ligands and zinc complexes. The theoretical results were compared with experimental data derived from UV−visible absorption and magnetic circular dichroism spectroscopy. Seven popular exchange-correlation functionals (BP86, B3LYP, TPSSh, M06, CAM-B3LYP, LC-BLYP, and ωB97X) were tested within these four approaches starting at a relatively modest level using 6-31G(d) basis sets and gas-phase BP86/def2-SVP optimized geometries. A gradual augmentation of the computational levels was used to identify the influence of starting geometry, solvation effects, and basis sets on the results of TD-DFT and sTD-DFT calculations. It was found that although these factors do influence the predicted energies of the vertical excitations, they do not affect the trends predicted in the spectral properties across series of structurally related substituted free bases and metallophthalocyanines. The best accuracy for the gas-phase vertical excitations was observed in the lower-energy Q-band region for calculations that made use of range-separated hybrids for both full and simplified TD-DFT approaches. The CAMB3LYP functional provided particularly accurate results in the context of the sTD-DFT approach. The description of the higherenergy B-band region is considerably less accurate, and this demonstrates the need for further advances in the accuracy of theoretical calculations. Together with a general increase in accuracy, the application of simplified TD-DFT methods affords a 2−3 orders of magnitude speedup of the calculations in comparison to the full TD-DFT approach. It is anticipated that this approach will be widely used on desktop computers during the interpretation of UV−vis−NIR spectra of phthalocyanines and related macrocycles in the years ahead