Simkine 2 – Versatile Software for the Computation of Kinetic Profiles of Intricate Chemical Reaction Mechanisms

Simkine 2 is a user-friendly software package developed with the Delphi 5 programming language, for the computation of complex reaction profiles based on a proposed kinetic scheme for the chemical system. The programme applies the semi-implicit extrapolation method (SIEM), which utilizes the implicit midpoint rule and extrapolation. Pre-processor code was designed to translate a user-specified system of chemical rate equations into a system of differential equations. To optimize the estimated rate coefficients manually, Simkine 2 provides a window simultaneously to plot the experimental and corresponding simulated curves in a single run. The software is applied to an intricate 17-step mechanism of the reaction between safranine-O and acidic bromate, which exhibits non-linear kinetics. The four simultaneously plotted computed curves with their experimental profiles are presented as an illustration. A help file is provided.KEYWORDS: Chemical kinetics, computation, simulations, reaction mechanisms, safranine-O and acidic bromate reaction

Mechanism of Oxidation of Brilliant Cresyl Blue with Acidic Chlorite and Hypochlorous Acid. A Kinetic Approach

The kinetics and mechanism of oxidation of brilliant cresyl blue (7-amino-3-diethylamino-8-methyl-phenoxazine chloride) (BB+) by chlorite in the presence of acid is reported. Under [H+]0>[ClO2–]0>[BB+]0 conditions, the oxidation reaction followed pseudo first-order kinetics with respect to BB+. During the reaction, chlorite ion disproportionates, resulting in accumulation of chlorine dioxide. The overall reaction is third-order with first-order dependence on both H+ and ClO2– ions. The rate coefficient for the overall reaction is (0.158 ± 0.003) l2 mol–2 s–1. The stoichiometry of the reaction is 2BB+ + 7ClO2 – + 2H+  2P + → 2CH3COOH + 4ClO2 + 3Cl– where P=7-amino-3-ethylamino-8-methyl-phenoxazine-10-N-oxide, and it varied with the initial concentrations of chlorite and acid. Near neutral pH, the hypochlorite-initiated oxidation of BB+ proceeded through two second-order pathways, one driven by OCl– ion and the other by HOCl. The latter reaction is much faster, with k=(1.26±0.04)×103 l mol–1 s–1. At low pH, the reaction was much faster and had first-order dependence on the concentrations of BB+, H+ and HOCl. Ru(III) catalysed the BB+-chlorite reaction with efficiency and the kinetics of the catalysed reaction are reported. Ru(III) had a catalytic constant, kCAT=1.2 × 106 l3 mol–3 s–1. The activation parameters for both uncatalysed and catalysed reactions were also reported. The kinetic profiles of the title reaction were computed using the proposed 11-step mechanism and Simkine software. The simulated curves agreed well with the experimental curves.Keywords: Kinetics, reaction mechanisms, dyes, water chemistry, computer chemistry

Kinetics and Mechanism of the Oxidation of Coomassie Brilliant Blue-R Dye by Hypochlorite and Role of Acid Therein

The kinetics of the oxidation of a triphenylmethane dye, Brilliant Blue-R (BB–Na+), in aqueous solution by hypochlorite as a function of pH was investigated. While the degradation of dye obeyed pseudo-first-order kinetics, the oxidation of the dye occurred through two competitive reactions facilitated by [OCl–] and [HOCl]. Both reactions exhibited first-order dependence on [OCl–] and [HOCl], respectively, but the hypochlorous acid initiated reaction was about ten times faster. The relative importance of the two paths rested on the pH-dependent concentrations of hypochlorite and hypochlorous acid. The overall second-order rate constants for the OCl– and HOCl initiated reactions are 1.2±0.2M–1 s–1 and 22.2±1.2M–1 s–1, respectively. The reaction energy parameters were determined as Ea=35.5 kJ mol–1,ΔHt=33.1 kJ mol–1 and ΔSt=–191.9 JK–1 mol–1 for the OCl– driven oxidation; and Ea= 26.8 kJ mol–1, ΔHt=29.3 kJ mol–1 and ΔSt=–204.6 JK–1 mol–1 for the HOCl facilitated reaction. The governing rate law and probable reaction mechanism were elucidated and validated by simulation. The three main oxidation products were 4-(4-ethoxyphenylamino)benzoic acid, 3-[(ethyl-hydroxyamino)methyl]benzene sulfonic acid and 6’-chloro-5’-hydroxybicyclohexylidene-2,5,2’-triene-4,4’-dione.KEYWORDS Brilliant Blue-R, oxidative degradation, hypochlorite, hypochlorous acid, kinetics, simulations.PDF and Supp files attache

Smokers' interest in a lung cancer screening programme: a national survey in England.

Following the recommendation of lung cancer screening in the US, screening committees in several European countries are reviewing the evidence for implementing national programmes. However, inadequate participation from high-risk groups poses a potential barrier to its effectiveness. The present study examined interest in a national lung cancer screening programme and modifiable attitudinal factors that may affect participation by smokers.A population-based survey of English adults (n = 1464; aged 50-70 years) investigated screening intentions in different invitation scenarios, beliefs about lung cancer, early detection and treatment, worry about lung cancer risk, and stigma. Data on smoking status and perceived chances of quitting were also collected, but eligibility for lung screening in the event of a national programme was unknown.Intentions to be screened were high in all three invitation scenarios for both current (≥ 89%) and former (≥ 94%) smokers. However, smokers were less likely to agree that early-stage survival is good (43% vs. 53%; OR: 0.64, 0.46-0.88) or be willing to have surgery for an early stage, screen-detected cancer (84% vs. 94%; OR: 0.38, 0.21-0.68), compared with former smokers. Willingness to have surgery was positively associated with screening intentions; with absolute differences of 25% and 29%. Worry about lung cancer risk was also most common among smokers (48%), and one fifth of respondents thought screening smokers was a waste of NHS money.A national lung cancer screening programme would be well-received in principle. To improve smokers' participation, care should be taken to communicate the survival benefits of early-stage diagnosis, address concerns about surgery, and minimise anxiety and stigma related to lung cancer risk

Array-based DNA methylation profiling of primary lymphomas of the central nervous system

<p>Abstract</p> <p>Background</p> <p>Although primary lymphomas of the central nervous system (PCNSL) and extracerebral diffuse large B-cell lymphoma (DLBCL) cannot be distinguished histologically, it is still a matter of debate whether PCNSL differ from systemic DLBCL with respect to their molecular features and pathogenesis. Analysis of the DNA methylation pattern might provide further data distinguishing these entities at a molecular level.</p> <p>Methods</p> <p>Using an array-based technology we have assessed the DNA methylation status of 1,505 individual CpG loci in five PCNSL and compared the results to DNA methylation profiles of 49 DLBCL and ten hematopoietic controls.</p> <p>Results</p> <p>We identified 194 genes differentially methylated between PCNSL and normal controls. Interestingly, Polycomb target genes and genes with promoters showing a high CpG content were significantly enriched in the group of genes hypermethylated in PCNSL. However, PCNSL and systemic DLBCL did not differ in their methylation pattern.</p> <p>Conclusions</p> <p>Based on the data presented here, PCNSL and DLBCL do not differ in their DNA methylation pattern. Thus, DNA methylation analysis does not support a separation of PCNSL and DLBCL into individual entities. However, PCNSL and DLBCL differ in their DNA methylation pattern from non- malignant controls.</p

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Nonlinear Kinetics and Mechanism of Nile Blue Reaction with Acidic Bromate and with Aqueous Bromine

Nile blue, a dye of the phenoxazine class follows complex kinetics during its reaction with bromate in acidic solutions. The reaction kinetics were investigated using photometric and potentiometric techniques and a stopped flow apparatus. Under excess acid and bromate concentration conditions, nile blue, (NB+) initially depletes very slowly. After an induction period, a swift reaction occurs. The overall reaction is NB+ + BrO3- react to P + CH3COOH + H+ + Br-, where P is the de-ethylated N-oxide derivative of nile blue. The rapid kinetics of the reaction of bromine direct with nile blue were also reported. A 11-step mechanism, consistent with the overall reaction dynamics and supported by simulations, is described. The role of various bromo- and oxybromo- species is discussed. South African Journal of Chemistry Vol.54 2001: 41-5