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PubMed2006

Oxidative addition of phenyl bromide to Pd(BINAP) vs Pd(BINAP)(amine). Evidence for addition to Pd(BINAP).

The rates of oxidative addition of phenyl bromide to [Pd(BINAP)2] have been measured in the presence and absence of added amine to assess a previous hypothesis that addition to [Pd(BINAP)(amine)] is faster than addition to [Pd(BINAP)]. These data show that addition to the amine complex is not faster than addition to [Pd(BINAP)]. Instead, they are consistent with oxidative addition, even in the presence of amine, to [Pd(BINAP)] as the major pathway. These data underscore the value of studying the stoichiometric reactions of isolated complexes when assessing the mechanism of a catalytic process.

Benzene Derivatives↗
PubMed1991

Rapid inversion of additive by additive relationship matrices by including sire-dam combination effects.

Inverses of relationship matrices are useful for prediction of individual additive or nonadditive genetic merits and for estimation of variance components. An algorithm to form inverses of additive by additive relationship matrices rapidly from lists of individuals and their parents was developed. The algorithm uses simple recurrences among additive by additive and sire-dam combination effects to construct inverses for noninbred or inbred populations. Dimensions of matrices produced may be several times the number of individuals in the population because combination effects for sire-dam subclasses must be included in matrices. Rules of inheritance of sire-dam combination effects are the same as for dominance combination effects. Cost of forming inverses increases linearly with number of individuals. Each individual contributes 36 or fewer nonzero coefficients, and each sire-dam subclass contributes an additional 81 or fewer nonzero coefficients to the matrix. Computation of inverse of the relationship matrix due to 1003 sires and maternal grandsires of 765,868 cows required forming a matrix of order 137,830 and 4 Mbytes of memory.

Algorithms↗
PubMed1990

The generality of mental addition models: simple and complex addition in a decision-production task.

Recently, Widaman, Geary, Cormier, and Little (in press) offered a general componential model for simple and complex addition. In the present study, the generalizability of this model to very complex addition problems and to production task performance was tested. We investigated addition-production performance using a new research paradigm, the decision-production task. The paradigm was used to assess the reaction times of 16 adults to 100 single-digit addition problems (Experiment 1) and to very complex three-digit addition problems (Experiment 2). Generally, the results give evidence for the basic assumptions of the Widaman et al. model. Some of the results, however, demonstrate that short-term memory load factors and strategy choices also have important effects on complex addition-production performance. Furthermore, the results of both experiments indicate that, in production tasks, the nature of the elementary search/compute process can be characterized as a memory-retrieval process and that the decision-production paradigm is a valuable alternative to the classical verbal production paradigm.

Adult↗
PubMed1999

Evaluation of certain food additives and contaminants. Forty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives.

This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives and contaminants, with a view to recommending acceptable daily intakes for humans, and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of food additives and contaminants, including flavouring agents, and the establishment and revision of specifications, with comments concerning limits for arsenic, lead and other heavy metals, and enzymes derived from genetically manipulated organisms. A summary follows of the Committee's evaluations of toxicological data on various specific food additives (tert-butylhydroquinone (TBHQ), microcrystalline cellulose, sucrose esters of fatty acids and sucroglycerides, alpha-acetolactate decarboxylase, maltogenic amylase, trans-anethole, hydrogenated poly-1-decene and maltitol syrup), food ingredients (short- and long-chain acyltriglycerides), flavouring agents and the contaminants aflatoxins. Annexed to the report are tables summarizing the Committee's recommendations for acceptable daily intakes of the food additives and food ingredients considered, changes in the status of specifications for these substances and specific flavouring agents, and further toxicological studies required.

Flavoring Agents↗
PubMed2002

Evaluation of certain food additives. Fifty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of food additives and contaminants (including flavouring agents), and the establishment and revision of specifications. A summary follows of the Committee's evaluations of toxicological data on various specific food additives (alitame, cross-linked sodium carboxymethyl cellulose, mineral oils (low- and medium-viscosity), nitrate, nitrite, and salatrim and six groups of flavouring agents). Annexed to the report are tables summarizing the Committee's recommendations for ADIs of the food additives and recommendations on the flavouring agents considered, changes in the status of specifications, further information required or desired, and a summary of conclusions on flavouring agents with minimum assay values of 95% or less.

Animals↗
PubMed2001

Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.

BACKGROUND: Anti-leukotriene (AL) agents are being considered as "add-on" therapy to inhaled corticosteroids (ICS), in chronic asthma. OBJECTIVES: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma. SEARCH STRATEGY: We searched Medline, Embase, Cinahl (all up to 2001), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and ATS meeting abstracts (1998-2000). SELECTION CRITERIA: Randomised placebo-controlled trials of asthmatics aged 2 years and older lasting at least one month. DATA COLLECTION AND ANALYSIS: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double). MAIN RESULTS: Of 336 citations, 11 trials (only adults) met inclusion criteria. Six were published in full-text, eight were high quality. Daily dose of ICS was 300-2000 mcg beclomethasone-equivalent. In symptomatic adults, AL (at 2-4 times licensed dose) combined with ICS reduced the number of patients with exacerbations that required systemic corticosteroids, compared to ICS alone [Relative Risk (RR) = 0.34; 95% Confidence Interval (CI) 0.13, 0.88]. This equates to 20 patients (95% CI 1,100 patients) treated to prevent one needing systemic corticosteroids. There was no difference in side effects. No trials tested the efficacy of licensed doses of ALs as add-on to ICS. In symptomatic adults, addition of zafirlukast to ICS did not reduce the number of exacerbations requiring systemic corticosteroids, compared to doubled dose ICS [RR= 1.39; 95% CI: 0.63, 3.08)]. There were no differences in any other measure of outcome. Higher doses of zafirlukast than currently licensed were associated with increased risk of liver enzyme elevation. In ICS-sparing trials of AL agents there was no difference in ICS dose after 12-16 weeks [Weighted Mean Difference (WMD) 1.9% change; 95% CI -3.5, 7.3], and no difference in lowest tolerated dose of ICS [WMD= 44 mcg/d; 95% CI -59, 148)]. REVIEWER'S CONCLUSIONS: Used as add-on therapy to inhaled corticosteroids, high dose anti-leukotrienes reduced exacerbations, but there is no evidence to support their use at currently licensed doses. There is insufficient evidence to indicate whether they confer benefit over doubling the dose of corticosteroids. There is no evidence that they have any significant inhaled corticosteroid-sparing effect.

Administration, Inhalation↗
PubMed1995

Additivity and non-additivity between dopamine-, norepinephrine-, carbachol- and GABA-stimulated GTPase activity.

The mode of coupling between neurotransmitter receptors and G proteins was investigated by agonist-induced high-affinity GTPase activity in rat striatal membranes. There was a simple additive relationship among dopamine-, carbachol-, and gamma-aminobutyric acid (GABA)-sensitive high-affinity GTPase activity in any combination, indicating that the respective receptors stimulated by these agonists (i.e., dopamine D2, pirenzepine-insensitive muscarinic, and GABAB receptors) interact independently with distinct pools of G proteins. Unexpectedly non-additivity was observed between dopamine- and norepinephrine-stimulation. This lack of additivity was apparently due to stimulation of the same dopamine D2 receptors by both dopamine and norepinephrine, since norepinephrine-stimulated high-affinity GTPase activity could be inhibited by dopaminergic but not adrenergic antagonists. The same non-additivity as seen in rat striatum was confirmed in the membranes prepared from cultured mouse fibroblast cells co-transfected with dopamine D2 and adenosine A2A receptors. The implication of the (non-)additivity between receptor-mediated high-affinity GTPase activity was discussed with a consideration of the possible underlying molecular mechanism.

Adrenergic Agonists↗
PubMed2005

Halobenzenes and Ir(I): kinetic C-H oxidative addition and thermodynamic C-Hal oxidative addition.

A (PNP)Ir fragment undergoes facile, room-temperature oxidative addition of C-H bonds in arenes and haloarenes in preference to aromatic carbon-halogen bonds. This preference, however, is determined to be kinetic in nature. Oxidative addition of C-Cl and C-Br is preferred thermodynamically. The products of the C-Cl or C-Br oxidative addition are separated from the C-H oxidative addition products by a high activation barrier and are only accessible at >100 degrees C. Of the C-H oxidative addition products of chlorobenzene, the isomer with the o-ClC6H4 ligand has the lowest energy.

Journal Article↗
PubMed2006

Thiazolium-catalyzed additions of acylsilanes: a general strategy for acyl anion addition reactions.

A strategy utilizing N-heterocyclic carbenes (NHCs) derived from thiazolium salts has been developed for the generation of carbonyl anions from acylsilanes. Synthetically useful 1,4-diketones and N-phosphinoyl-alpha-aminoketones have been prepared in good to excellent yields via NHC-catalyzed additions of acylsilanes to the corresponding alpha,beta-unsaturated systems and N-phosphinoylimines. These organocatalytic reactions are air- and water-tolerant methods to execute robust carbonyl anion addition reactions. Additionally, polysubstituted aromatic furans and pyrroles have been efficiently synthesized in a one-pot process using this carbonyl anion methodology. The addition of alcohols to the reaction renders the process catalytic in thiazolium salt. In an effort to synthesize a potential intermediate along the proposed reaction pathway, silylated thiazolium carbinols have been identified to provide good yields of carbonyl anion addition products when subjected to the standard reaction conditions in the presence of suitable electrophiles.

Journal Article↗
PubMed2005

The kinetics of addition and fragmentation in reversible addition fragmentation chain transfer polymerization: An ab initio study.

High-level ab initio calculations of the forward and reverse rate coefficients have been performed for a series of prototypical reversible addition fragmentation chain transfer (RAFT) reactions: R* + S=C(Z)SCH3 --> R-SC*(Z)SCH3, for R = CH3, with Z = CH3, Ph, and CH2Ph; and Z = CH3, with R = (CH3), CH2COOCH3, CH2Ph, and C(CH3)2CN. The addition reactions are fast (ca. 10(6)-10(8) L mol(-1) s(-1)), typically around three orders of magnitude faster than addition to the C=C bonds of alkenes. The fragmentation rate coefficients are much more sensitive to the nature of the substituents and vary from 10(-4) to 10(7) s(-1). In both directions, the qualitative effects of substituents on the rate coefficients largely follow those on the equilibrium constants of the reactions, with fragmentation being favored by bulky and radical-stabilizing R-groups and addition being favored by bulky and radical-stabilizing Z-groups. However, there is evidence for additional polar and hydrogen-bonding interactions in the transition structures of some of the reactions. Ab initio calculations were performed at the G3(MP2)-RAD//B3-LYP/6-31G(d) level of theory, and rates were obtained via variational transition state theory in conjunction with a hindered-rotor treatment of the low-frequency torsional modes. Various simplifications to this methodology were investigated with a view to identifying reliable procedures for the study of larger polymer-related systems. It appears that reasonable results may be achievable using standard transition state theory, in conjunction with ab initio calculations at the RMP2/6-311+G(3df,2p) level, provided the results for delocalized systems are corrected to the G3(MP2)-RAD level using an ONIOM-based procedure. The harmonic oscillator (HO) model may be suitable for qualitative "order-of-magnitude" studies of the kinetics of the individual reactions, but the hindered-rotor (HR) model is advisable for quantitative studies.

Journal Article↗
PubMed2001

Additive and non-additive genetic architecture of two different-sized populations of Scabiosa canescens.

Future adaptation to changes in the environment depends on the existence of additive genetic variances within populations. Recently, considerable attention has also been given to the non-additive component, which plays an important role in inbreeding depression and bottleneck situations. In this study, I used data from a North Carolina II crossing experiment, analysed with restricted maximum-likelihood methods, to estimate the additive and dominance genetic (co)variances for eight quantitative characters in two different-sized populations of Scabiosa canescens, a rare and threatened plant in Sweden. There was no evidence for genetic erosion in the small Hällestad population ( approximately 25 individuals) relative to the large Ahus population ( approximately 5000 individuals). In fact, slightly higher heritabilities were found in the Hällestad population. The additive genetic variance was statistically significant for all traits in both populations, but only a few additive covariances reached significance. The Hällestad population also had higher mean levels and more traits with significant dominance variance than the Ahus population. The variance attributable to maternal effects was too low to be considered significant. There was only a weak correspondence between heritabilities for each trait in the present study and previous estimates based on open-pollinated families of the same populations, but the mean heritability (over characters) was consistent between the studies.

Analysis of Variance↗
PubMed1993

Additive risk versus additive relative risk models.

The distinction between additive risk models and additive relative risk models is important when nonadditivity is used as a criterion for interdependence of causal effects (causal interaction). I show here that, in stratified studies, additive relative risk models do not provide the often-assumed correspondence between additivity and absence of causal interaction. Under the causal models of Rothman and others, complete assessment of causal interaction requires that one fit additive risk models; in matched case-control studies, such fitting may require external information.

Causality↗
PubMed2003

Transmission of alien chromosomes from selfed progenies of a complete set of Allium monosomic additions: the development of a reliable method for the maintenance of a monosomic addition set.

Selfed progeny of a complete set of Allium fistulosum - Allium cepa monosomic addition lines (2n = 2x + 1 = 17, FF+1A-FF+8A) were produced to examine the transmission rates of respective alien chromosomes. All eight types of the selfed monosomic additions set germinable seeds. The numbers of chromosomes (2n) in the seedlings were 16, 17, or 18. The eight extra chromosomes varied in transmission rate (%) from 9 (FF+2A) to 49 (FF+8A). The complete set of monosomic additions was reproduced successfully by self-pollination. A reliable way to maintain a set of Allium monosomic additions was developed using a combination of two crossing methods, selfing and female transmission. FF+8A produced two seedlings with 18 chromosomes. Cytogenetical analyses, including GISH, showed that the seedlings were disomic addition plants carrying two entire homologous chromosomes from A. cepa in an integral diploid background of A. fistulosum. Flow cytometry analysis showed that a double dose of the alien 8A chromosome caused fluorescence intensity values spurring in DNA content, and isozyme analysis showed increased glutamate dehydrogenase activity at the gene locus Gdh-1.

Allium↗
PubMed1998

Comparison of 2 treatment strategies for depressed inpatients: imipramine and lithium addition or mirtazapine and lithium addition.

BACKGROUND: The purpose of this study was to compare the overall effectiveness of 2 treatment strategies for inpatients with severe major depressive episode (DSM-III-R): (1) mirtazapine (phase 1) and subsequent lithium addition (phase 2) or (2) imipramine (phase 1) and subsequent lithium addition (phase 2). We previously reported the results of phase 1. METHOD: In phase 1, patients were randomly assigned to treatment with either mirtazapine or imipramine, and doses were adjusted to obtain predefined blood drug levels. Nonresponders had lithium added to the double-blind mirtazapine or imipramine medication. The dose was adjusted to obtain a blood lithium level of 0.5-1.0 mmol/L. Treatment effects were evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this blood lithium level. RESULTS: Data for 100 patients were available for comparison of the 2 treatment strategies. 80 patients received no comedication. By the end of phase 2, 24 (48%) of 50 had responded to mirtazapine and 32 (64%) of 50 had responded to imipramine (intent-to-treat analysis). A survival analysis of the total patient group intent-to-treat showed a significant difference in favor of the treatment strategy with imipramine and subsequent lithium addition. CONCLUSION: Efficacy of imipramine and subsequent lithium addition for nonresponders is superior to the same treatment strategy with mirtazapine. This applies to the patient sample studied, which consisted of 100 severely depressed inpatients, 29 of whom were psychotically depressed. More serious side effects of imipramine, however, led to discontinuation of imipramine in 5 patients. No serious side effects were observed during the phase of lithium addition to either imipramine or mirtazapine. We, therefore, prefer to start treatment with imipramine and test for fixed blood drug levels, and, if necessary, add lithium. In the case of prohibitive side effects, patients are switched to a modern antidepressant such as mirtazapine, and, if necessary, lithium is added to this antidepressant.

Adult↗
PubMed2003

Bilateral additional renal arteries and an additional right renal vein associated with unrotated kidneys.

We report a rare anomaly of the kidneys and its vessels, which were found during the routine dissection of a 68-year-old male cadaver. The anomaly consisted of bilateral additional renal arteries originating from the abdominal aorta and an additional right renal vein accompanying the additional right renal artery. These anomalies were associated with unrotated kidneys with extrarenal calices and pelves. All the additional vessels were located posterior to the ureter with a close relationship to the ureteropelvic junction on the right side. Additional renal vessels arise as a result of the complicated development of kidneys and variations in the positional anatomy of the kidneys, and their vascular supply are of clinical importance.

Aged↗
PubMed2004

The development of experimental procedures for the evaluation of additives to attenuate manure odour, and the impact of these additives on workers, animals and the environment.

The objective of this project was to develop a laboratory research protocol to evaluate the effect of additives on manure odour and physico-chemical characteristics, and establish conditions that are representative of those found in farm storage structures (temperature, solids content, pH, ventilation above the manure surface, storage period). The results suggested that system configuration might have an impact on additive effect. An open system should be used when it is recommended that additives be applied in the animal diet or the gutters. Additionally, the surface/depth ratio of the gutter should be respected, since it will impact on the relative importance of the aerobic layer and on ammonia volatilization. On the other hand, a closed system should be used when the additive is applied to the manure storage tank, especially if the tank has a cover. Odour analysis still requires fundamental research to establish reliable procedures and protocols, especially in the area sample collection and dilution levels required to decrease H2S concentration to safe levels for the panellists. Odour analysis should also be conducted in triplicate, because of the possible large experimental error due to dilution, the human factors, and also instrumental error.

Ammonia↗
PubMed1990

Toxicological evaluation of food additives. Toxicological evaluation over estimation of potential high intake to permitted levels of use of food additives and vice versa.

Permitted levels of use for food additives should agree with the acceptable daily intakes (ADIs) established by toxicologists. To ensure accordance, nutritional and physiological factors can be used to estimate high intakes of food and beverages. Appetite and thirst (energy and liquid requirements) are such quantitative factors. They are universal and, if placed on the same level as the ADI, i.e., expressed on a kilogram of body weight basis, can be used to estimate high intakes of an additive. This tool can be easily used to judge whether a suggested level of use may cause consumption of the additive to exceed the ADI. It also tells us to what level (ADI) toxicological clearance should be sought, when the technological need is known. The method is independent of food consumption surveys, but these may be carried out to confirm its forecasts. This paper uses caramel in soft drinks as an example. The approach, also called "the budget method," has been tried out in Denmark and Sweden. It is now being offered as a solution to the problem facing the European Communities: to establish before 1993 a common list of food additives containing quantitative limitations for use.

Appetite↗
PubMed1978

Symposium: wise use of chemicals, drugs, and additives by dairy producers. Clearance procedures for new animal drugs and feed additives.

We have attempted to provide an overview of the Food, Drug, and Cosmetic Act as it pertains to animal drugs and feed additives. The Act requires that each new animal drug application or food additive petition contain sufficient data to prove that the drug or feed additive is safe and effective before the drug or feed additive can be marketed. It also gives the Secretary of Health, Education, and Welfare the power to remove from the market a previously accepted drug if it is shown to be unsafe or lacks effectiveness. The Bureau of Veterinary Medicine has prepared guidelines to aid applicants in compiling ans submitting the necessary information for approval of drugs to be used in dairy cattle. A copy of these guidelines and a Drug Use Guide, which aids the dairymen to correctly use approved drugs, can be obtained from the Bureau.

Animal Feed↗