Managing R&D alliances within government: the "virtual agency" concept

The virtual agency concept is now used within the United States Government as an alliance approach to manage large research and development (R&D) processes across departments. This paper examines the history of the virtual agency concept and its important characteristics. The paper identifies the potential benefits and associated risks involved in managing R&D within a virtual agency. Three cases are examined where the virtual agency concept has been applied to R&D programs: the High Performance Computing and Communications initiative, the Next Generation Internet, and the Partnership for a New Generation of Vehicles. The case studies indicate that the R&D process is attempting to balance formal process controls with the agility to adapt rapidly to new research opportunities. Virtual agencies can be used to improve organizational efficiency, improve knowledge transfer, increase interoperability through standards, provide better alignment of agency missions with national policy, and introduce increased flexibility into the R&D process. At the same time, the virtual agency concept has major risks including inefficiencies due to organizational complexity, the danger of collective myopia, the problem of adopting standards too early, the difficulty of reaching objectives in a loose organizational structure, and the problem of properly balancing the tension between agency mission objectives and national policy agendas.     

Risk factors for a medically inappropriate admission to a Department of Internal Medicine

OBJECTIVE: To identify patient- and admission-related risk factors for a medically inappropriate admission to a department of internal medicine. METHODS: Cross-sectional study of a systematic sample of 500 admissions to the department of internal medicine of an urban teaching hospital. The appropriateness of each admission and reasons for inappropriate admissions were assessed using the Appropriateness Evaluation Protocol. Risk factors included the time (day of week and holidays) and manner (through emergency department or direct admission) of admission, patient age and sex, health status of patient and spouse, living arrangements, formal home care services, and informal support from family or friends. RESULTS: Overall, 76 (15.2%) hospital admissions were rated as medically inappropriate by the Appropriateness Evaluation Protocol. In multivariate analysis, the likelihood of an inappropriate admission was increased by better physical functioning of the patient (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.1 [for 1 SD in Physical Functioning scores]), lower mental health status of the patient's spouse (OR, 2.6; 95% CI, 1.3-5.6), receipt of informal help from family or friends (OR, 3.3; 95% CI, 1.5-7.2), and hospitalization by one's physician (OR, 3.6; 95% CI, 1.7-7.5). Receiving formal adult home care was not associated with inappropriateness of hospitalization. CONCLUSIONS: Inappropriate admissions to internal medicine wards are determined by a mix of factors, including the patient's health and social environment. In addition, the private practitioners' discretionary ability to hospitalize their patients directly may also favor medically inappropriate admissions.     

The ability of the rat to metabolize myristoyl-methionine: an acylamino acid with potentially useful antibacterial properties

Two experiments with Sprague Dawley rats tested their ability to hydrolyse myristoyl-methionine (M-M) into myristic acid and L-methionine (M). In the first experiment, lasting for 3 days. male rats were orally administered [9,10-3H]myristoyl-L-[35S]methionine. The recovery of radioactivity was approximately 90% for both isotopes; 19% of the administered 3H was recovered in the urine and 16% in the faeces, while the recovered 35S activity was 13 and 12%, respectively. The balance of the radioactivity was found among the tissues, organs and blood. In the second experiment, male and female rats received soybean-based diets which were supplemented with either 0.305% M-M or 0.2% M (both diets contained equal amounts of M) for periods up to 4 weeks. The growth rate of the rats receiving the 0.305% M-M diets was slightly slower than that for the rats on the 0.2% M diet, but the difference was not statistically significant (P > 0.05). The M-M rats had a transitory decrease in feed consumption, suggesting that palatability may have contributed to the growth difference and that a somewhat greater amount of M-M was necessary for the rat to attain the same growth rate as that produced by 0.2% M. When the amount of dietary M-M was increased to 3.05% M-M, a greater reduction in feed consumption and body weight gain was observed. This latter diet was an initial attempt to study the potential toxicity of M-M. None of the haematological, clinical chemistry or organ weight data suggested that M-M was overtly toxic per se, but longer-term feeding studies are needed to evaluate the potential toxicity of M-M more fully.     

Kinetic analysis of the coding properties of O6-methylguanine in DNA: the crucial role of the conformation of the phosphodiester bond

Production by N-nitroso compounds of O6-alkylguanine (O6-alkylG) in DNA directs the misincorporation of thymine during DNA replication, leading to G:C to A:T transition mutations, despite the fact that DNA containing O6-alkylG:T base pairs is less stable than that containing O6-alkylG:C pairs. We have examined the kinetics of incorporation by Klenow fragment (KF) of Escherichia coli DNA polymerase I of thymine (T) and of cytosine (C) opposite O6-MeG in the template DNA strand. Both T and C were incorporated opposite O6-MeG much slower than nucleotides forming regular A:T or G:C base pairs. Using various concentrations of dTTP, dCTP, or their phosphorothioate (Sp)-dNTP alpha S analogues, or a mixture of dTTP and dCTP, the progress of incorporation of a single nucleotide in a single catalytic cycle of a preformed KF-DNA complex was measured (pre-steady-state kinetics). The results were consistent with the kinetic scheme (Kuchta, R. D., Benkovic, P., & Benkovic, S. J. (1988) Biochemistry 27, 6716-6725): (1) binding of dNTP to polymerase-DNA; (2) conformational change in polymerase; (3) formation of phosphodiester between the dNTP and the 3'-OH of the primer; (4) conformational change of polymerase; (5) release of pyrophosphate. The results were analyzed mathematically to identify the steps at which the rate constants differ significantly between the incorporation of T and C. The only significant difference was the 5-fold difference in the rates of formation of the phosphodiester bond (for dTTP, kforward = 3.9 s-1 and kback = 1.9 s-1; for dCTP, kforward = 0.7 s-1 and kback = 0.9 s-1). These pre-steady-state progress curves were biphasic with a rapid initial burst followed by an apparently steady-state rise. Deconvolution of these curves gave direct evidence for the importance of the conformational change after polymerization by showing that the curves represented the sum of the rapid accumulation of the product of step 3 followed by the slow conversion of that to the product of step 5 (because of the rapidity of the release of pyrophosphate there was no significant accumulation of the product of step 4). The equilibrium constants for each step suggest that the greatest change in the Gibbs free energy occurs at the conformational change after polymerization and that while the formation of the phosphodiester bond to T is slightly exothermic, that to C is slightly endothermic.(ABSTRACT TRUNCATED AT 400 WORDS)     

Determination of the relative amounts of free and complexed manganese ions in aqueous solution by nuclear magnetic resonance.

The ratio of the transverse relaxation rate to the longitudinal relaxation rate of water protons (T1/T2) at 90 MHz can be used to determine the relative amounts of free Mn2+ ions (the hexaquo ion) and chelated manganese ions when both species are present in the same aqueous solution. This technique is demonstrated for simple aqueous solutions containing known concentrations of both the free Mn2+ ion and a manganese(III) porphyrin. The accuracy of the method is found to be +/- 7.3% for the solutions considered in this report. The determinations of the relative amounts of the free Mn2+ ion and the manganese(III) porphyrin by this T1/T2 method are shown to agree well with those determined by nuclear magnetic resonance dispersion profiles. The theoretical basis of this ratio method as well as the scope and limitations in its application to aqueous solutions containing both free Mn2+ ions and chelated manganese species other than manganese(III) porphyrins are also discussed. This work demonstrates a unique use of NMR as a means for the quantitative analysis of manganese in which the effects of the metal ion on the solvent, and not the metal itself, are observed.     

Short contact time dissolution of vitrinite and inertinite concentrates

The short contact time dissolution of vitrinite and inertinite concentrates of an Australian bituminous coal was studied under isothermal conditions with tetralin as solvent. The reactivity of the two maceral types and the yields and nature of the products were determined for a range of reaction temperatures (400, 420 and 440 °C) and reaction times (2–20 min). The dissolution of vitrinite proceeded at a significantly greater rate than for inertinite and was associated with greater selectivity to soluble non-gaseous products. At very short reaction times (2 min), the vitrinite underwent solubilizing reactions to yield products of higher molecular weight and greater oxygen functionality than was the case for inertinite, for which changes in the chemical nature of the products were negligible over the range of conditions studied. At longer reaction times (5 min), the composition of the vitrinite-derived products was similar to that of the inertinite-derived products.     

High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis

OBJECTIVE: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. DESIGN: Case series. PARTICIPANTS: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. INTERVENTION: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. RESULTS: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). CONCLUSION: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs. inactive vs. control). These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response.