Особенности движения метановоздушной смеси в дегазационном трубопроводе

Розглянуто ізотермічне та неізотермічне турбулентний рух метаноповітряної суміші в дільничному дегазаційному трубопроводі.Isothermal and non isothermal considered the motion methane-air mixture in the decontamination line

Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP to GLU substitution in an intra-molecular salt-bridge network

Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity

Polarizabilities in the condensed phase and the local fields problem: A direct reaction field formulation

A consistent derivation is given for local field factors to be used for correcting measured or calculated static (hyper)polarizabilities in the condensed phases. We show how local fields should be used in the coupled perturbative Hartree–Fock or finite field methods for calculating these properties, specifically for the direct reaction field (DRF) approach, in which a quantum chemically treated “solute” is embedded in a classical “solvent” mainly containing discrete molecules. The derivation of the local fields is based on a strictly linear response of the classical parts and they are independent of any quantum mechanical method to be used. In applications to two water dimers in two basis sets it is shown that DRF matches fully quantum mechanical results quite well. For acetone in eleven different solvents we find that if the solvent is modeled by only a dielectric continuum (hyper)polarizabilities increase with respect to their vacuum values, while with the discrete model they decrease. We show that the use of the Lorentz field factor for extracting (hyper)polarizabilities from experimental susceptibilities may lead to serious errors

WHO guide to good prescribing is 25 years old:quo vadis?

Introduction: Twenty-five years ago, the World Health Organization (WHO) published the Guide to Good Prescribing (GGP), followed by the accompanying Teacher’s Guide to Good Prescribing (TGGP). The GGP is based on a normative 6-step model for therapeutic reasoning and prescribing, and provides a six-step guide for students to the process of rational prescribing. Method: We reviewed the need to update both WHO publications by evaluating their use and impact, including new (theoretical) insights and demands. Based on information from literature, Internet, and other (personal) sources, we draw the following conclusions. Results: 1. An update of the GGP and TGGP, both in terms of content and form, is necessary because of the current need for these tools (irrational medicine use and unavailability of medicines), the lack of similar documents, and the lack of connection with recent developments, such as Internet and modern education; 2. The basic (6-step) model of the GGP is effective in terms of rational prescribing in the undergraduate situation and is still consistent with current theories about (context) learning, clinical decision-making, and clinical practice; 3. The dissemination and introduction of the GGP and TGGP in education has been successful so far, but is still not optimal because of lack of support and cooperation. Conclusions: On the basis of the evaluation results, a plan for the revision of the GGP and TGGP is presented

Dead space and slope indices from the expiratory carbon dioxide tension-volume curve

The slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate (PIE), were investigated in 28 healthy control subjects, 12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately obstructed) with the aim to establish diagnostic value. Because breath volume and frequency are closely related to CO2 elimination, the recording procedures included varying breath volumes in all subjects during self-chosen/natural breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1) with varying breath volumes only in the healthy controls. From the relationships of the variables with tidal volume (VT), the values at 1 L were estimated to compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most significant difference between controls and patients with asthma or emphysema, compared to the other two dead space estimates, and were related to the degree of airways obstruction. Discrimination between no-emphysema (asthma and controls) and emphysema patients was possible on the basis of a plot of intercept and slope of the relationship between VD,Bohr and VT. A combination of both the slope of phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence of fixed frequencies in the controls did not change the results. The conclusion is that Bohr dead space in relation to tidal volume seems to have diagnostic properties separating patients with asthma from patients with emphysema with the same degree of airways obstruction. Equally discriminating was a combination of both phase 3 and Bohr dead space of a breath of 1 L. The different pathophysiological mechanisms in asthma and emphysema leading to airways obstruction are probably responsible for these results

Increased rate of respiratory symptoms in children with Down syndrome:A 2-year web-based parent-reported prospective study

To compare the incidence of respiratory symptoms and short-term consequences between children with Down syndrome and children from the general population, we conducted a prospective parent-reported observational study. Children with Down syndrome (≤ 18 years) were included between March 2012 and June 2014. Caregivers received a baseline questionnaire with follow-up 1-2 years after inclusion. Caregivers received a weekly questionnaire about respiratory symptoms, fever, antibiotic prescriptions, doctor's visits, and consequences for school and work attendance. Children with Down syndrome were compared to a cohort of the general population ("Kind en Ziek" study) with similar weekly questionnaires. A total of 9,011 childweeks were reported for 116 participants with Down syndrome (75% response rate). The frequency of respiratory symptoms was higher in children with Down syndrome than in children from the general population (30% vs 15.2%). In addition, symptoms subsided later (around 8 vs 5 years of age). The seasonal influence was limited, both in children with Down syndrome and children from the general population. Consequences of respiratory disease were significant in children with Down syndrome compared to children from the general population, with a higher rate of doctor's visits (21.3% vs 11.8%), antibiotic prescriptions (47.8% vs 26.3%), and absenteeism from school (55.5% vs 25.4%) and work (parents, 9.4% vs 8.1%). Conclusion: Children with Down syndrome have a higher frequency of respiratory symptoms and symptoms last until a later age, confirming the impression of professionals and caregivers. Individualized treatment plans might prevent unfavorable consequences of chronic recurrent respiratory disease in children with Down syndrome. What is Known: • Children with Down syndrome have an altered immune system and are prone to a more severe course of respiratory tract infections. • The overall conception is that patients with Down syndrome suffer from respiratory tract infections more often. What is New: • Children with Down syndrome suffer from respiratory symptoms more frequently than children from the general population. • The respiratory symptoms in children with Down syndrome subside at a later age compared to children from the general population

Herschel/PACS observations of the 69 μm\mu m band of crystalline olivine around evolved stars

We present 48 Herschel/PACS spectra of evolved stars in the wavelength range of 67-72 $\mu$m. This wavelength range covers the 69 $\mu$m band of crystalline olivine ($\text{Mg}_{2-2x}\text{Fe}_{(2x)}\text{SiO}_{4}$). The width and wavelength position of this band are sensitive to the temperature and composition of the crystalline olivine. Our sample covers a wide range of objects: from high mass-loss rate AGB stars (OH/IR stars, $\dot M \ge 10^{-5}$ M$_\odot$/yr), through post-AGB stars with and without circumbinary disks, to planetary nebulae and even a few massive evolved stars. The goal of this study is to exploit the spectral properties of the 69 $\mu$m band to determine the composition and temperature of the crystalline olivine. Since the objects cover a range of evolutionary phases, we study the physical and chemical properties in this range of physical environments. We fit the 69 $\mu$m band and use its width and position to probe the composition and temperature of the crystalline olivine. For 27 sources in the sample, we detected the 69 $\mu$m band of crystalline olivine ($\text{Mg}_{(2-2x)}\text{Fe}_{(2x)}\text{SiO}_{4}$). The 69 $\mu$m band shows that all the sources produce pure forsterite grains containing no iron in their lattice structure. The temperature of the crystalline olivine as indicated by the 69 $\mu$m band, shows that on average the temperature of the crystalline olivine is highest in the group of OH/IR stars and the post-AGB stars with confirmed Keplerian disks. The temperature is lower for the other post-AGB stars and lowest for the planetary nebulae. A couple of the detected 69 $\mu$m bands are broader than those of pure magnesium-rich crystalline olivine, which we show can be due to a temperature gradient in the circumstellar environment of these stars. continued...Comment: Accepted for publication in A&

Pruning the regulatory tree

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62897/1/457534a.pd