Model reduction of genome-scale metabolic models as a basis for targeted kinetic models.

Constraint-based, genome-scale metabolic models are an essential tool to guide metabolic engineering. However, they lack the detail and time dimension that kinetic models with enzyme dynamics offer. Model reduction can be used to bridge the gap between the two methods and allow for the integration of kinetic models into the Design-Built-Test-Learn cycle. Here we show that these reduced size models can be representative of the dynamics of the original model and demonstrate the automated generation and parameterisation of such models. Using these minimal models of metabolism could allow for further exploration of dynamic responses in metabolic networks.

Performance assessment of Vita Easy Shade spectrophotometer on colour measurement of aesthetic dental materials.

Four different shades were used to produce 20 samples of resin-based composite and 20 samples of porcelain to evaluate the performance ability of an intra oral test spectrophotometer compared to a reference spectrophotometer. The absolute colour coordinates CIELAB values measured with both spectrophotometers were significantly different (p < 0.001). However, a high correlation was found (p < 0.001) despite the low concordance noticed. The colour difference deltaE* values calculated between different shades also were significantly different between both spectrophotometers (p < 0.05). Therefore, the Easy Shade can be used in dental practice and dental research with some limitations.

Cognitive association formation in human memory revealed by spatiotemporal brain imaging.

Cognitive theory posits association by juxtaposition or by fusion. We employed the measurement of event-related brain potentials (ERPs) to a concept fusion task in order to explore memory encoding of these two types of associations between word pairs, followed by a memory test for original pair order. Encoding processes were isolated by subtracting fusion task ERPs corresponding to pairs later retrieved quickly from ERPs corresponding to pairs later retrieved slowly, separately for pairs fused successfully and unsuccessfully (i.e., juxtaposed). Analyses revealed that the encoding of these two types of associations yields different ERP voltage polarities, scalp topographies, and brain sources extending over the entire time course of processing.

Just add water: Accuracy of analysis of diluted human milk samples using mid-infrared spectroscopy.

OBJECTIVE: To determine the maximum dilution of human milk (HM) that yields reliable results for protein, fat and lactose when analyzed by mid-infrared spectroscopy. STUDY DESIGN: De-identified samples of frozen HM were obtained. Milk was thawed and warmed (40°C) prior to analysis. Undiluted (native) HM was analyzed by mid-infrared spectroscopy for macronutrient composition: total protein (P), fat (F), carbohydrate (C); Energy (E) was calculated from the macronutrient results. Subsequent analyses were done with 1 : 2, 1 : 3, 1 : 5 and 1 : 10 dilutions of each sample with distilled water. Additional samples were sent to a certified lab for external validation. RESULTS: Quantitatively, F and P showed statistically significant but clinically non-critical differences in 1 : 2 and 1 : 3 dilutions. Differences at higher dilutions were statistically significant and deviated from native values enough to render those dilutions unreliable. External validation studies also showed statistically significant but clinically unimportant differences at 1 : 2 and 1 : 3 dilutions. CONCLUSIONS: The Calais Human Milk Analyzer can be used with HM samples diluted 1 : 2 and 1 : 3 and return results within 5% of values from undiluted HM. At a 1 : 5 or 1 : 10 dilution, however, results vary as much as 10%, especially with P and F. At the 1 : 2 and 1 : 3 dilutions these differences appear to be insignificant in the context of nutritional management. However, the accuracy and reliability of the 1 : 5 and 1 : 10 dilutions are questionable.

THE PHE FORTUITOUS DOSIMETRY CAPABILITY BASED ON OPTICALLY STIMULATED LUMINESCENCE OF MOBILE PHONES.

The Public Health England fortuitous dosimetry capability is reviewed, with particular attention focussed on the derivation of its energy and fading corrections, the Monte Carlo techniques used to generate the calibration factors between phone and body doses, and the procedures set in place to facilitate a reliable and effective service.

The effects of pregnancy and lactation on the activities in rat liver of some enzymes associated with glucose metabolism.

1. The ratio of the combined activities of hexokinase (EC 2.7.1.1) and glucokinase (EC 2.7.1.2) to the activity of glucose-6-phosphatase (EC 3.1.3.9) changed in favour of the glycolytic enzymes during pregnancy and at peak lactation. 2. There were no important changes in the ratio of the activity of phosphofructokinase (EC 2.7.1.11) to that of fructose diphosphatase (EC 3.1.3.11). 3. The ratio of the activity of pyruvate kinase (EC 2.7.1.40) to the combined activities of phosphoenolpyruvate carboxylase (EE 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) changed in favour of the glycolytic enzyme during pregnancy and at peak lactation, but changed in favour of the gluconeogenic enzymes immediately after parturition. 4. These changes are considered in relation to the changes in food intake and hormonal status that occur during pregnancy and lactation.

Development of a retrospective/fortuitous accident dosimetry service based on OSL of mobile phones.

Work is presented on the development of a retrospective/fortuitous accident dosimetry service using optically stimulated luminescence of resistors found in mobile phones to determine the doses of radiation to members of the public following a radiological accident or terrorist incident. The system is described and discussed in terms of its likely accuracy in a real incident.

Regulation of cortical blood flow by the dorsal raphe nucleus: topographic organization of cerebrovascular regulatory regions.

We examined in rat: (1) the time-course and magnitude of change in cortical blood flow (CoBF) following electrical stimulation of the dorsal raphe nucleus (DRN) and (2) whether DRN lesions affect resting CoBF or the cerebrovascular response to CO2. Animals were anesthetized (chloralose), paralyzed, and artificially ventilated. The effect of stimulus frequency (1-200 Hz) and intensity (10-100 microA) on arterial pressure, heart rate, and CoBF was examined; lesions were made electrolytically. CoBF was measured using a laser-Doppler flowmeter with the probe placed extradurally over the parietal sensorimotor cortex. The DRN was computer reconstructed in three dimensions from Nissl stained coronal sections for localization of electrode placements. Brief stimuli (8 s; n = 6) elicited frequency and intensity-dependent increases in arterial pressure, heart rate, and CoBF. Sustained intermittent trains of stimuli of rostral DRN (200 Hz; 1 s on/1 s off; 70 microA) elicited a decrease (85 +/- 12% of baseline; n = 9) in CoBF (p less than 0.05) while stimulation in caudal DRN resulted in increased CBF (126 +/- 13% of baseline; n = 9). Phenylephrine infusion (0.1-1 microgram; i.v.; n = 8) increased arterial pressure and CoBF less than that elicited by brief DRN stimulation (p less than 0.05). DRN lesions did not affect resting CoBF (140 +/- 25 perfusion units (PU) before; 127 +/- 16 PU after DRN lesion; p greater than 0.05, n = 5) or mean arterial pressure (127 +/- 13 before; 120 +/- 11 after); nor did it affect the cerebrovascular response to change in arterial PCO2. Sustained intermittent stimulation of the DRN can evoke either increases or decreases in CoBF depending on the anatomical sublocalization. The DRN does not tonically maintain resting CoBF, nor participate in the cerebrovascular response to change in PCO2.

Control of complex formation of DNA polymerase alpha-primase and cell-free DNA replication by the C-terminal amino acids of the largest subunit p180.

DNA polymerase alpha-primase is a heterotetrameric complex essential for simian vacuolating virus 40 (SV40) DNA replication. We show that the C-terminal 67 amino acid residues of the human p180 subunit are essential for SV40 DNA replication as they are required for binding of the p68 subunit and play a role in the interaction with the primase subunits, p48 and p58. Furthermore, we demonstrate that exchanging these residues to those of mouse origin can only partially rescue the SV40 DNA replication activity of DNA polymerase alpha-primase.

N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides: KATP potassium channel openers. Modifications on the western region.

A subset of antiandrogen compounds, the N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides 1, were found to activate ATP sensitive potassium channels (KATP) and represent a new class of potassium channel openers (PCOs). A structure-activity relationship was carried out on the western region of this series with the goal of obtaining an activator of the ATP sensitive potassium channel suitable for use in the treatment of urge urinary incontinence. In particular three large 4-(N-aryl) substituents, the (N-phenyl-N-methylamino)sulfonyl, benzoyl, and 4-pyridylsulfonyl moieties, yielded non-antiandrogen, KATP potassium channel openers (39, 41, and 64, respectively) that are bladder selective in an in vivo rat model that simultaneously measures bladder contractions, heart rate, and blood pressure. Substitutions of the aryl rings of 41 and 64 gave several derivatives that also display selectivity in the in vivo rat model; however, none appear to offer a substantial advantage over 41 and 64. The PCO activity of 41 and 64 resides in the (S)-(-) enantiomers. ZD6169, 41(S), has been selected into development for the treatment of urge urinary incontinence.

The measurement of solute diffusion coefficients in dilute liquid alloys: the influence of unit gravity and g-jitter on buoyancy convection.

Liquid diffusion experiments conducted on the MIR space station using the Canadian Space Agency QUELD II processing facility and the microgravity isolation mount (MIM) showed that g-jitter significantly increased the measured solute diffusion coefficients. In some experiments, milli-g forced vibration was superimposed on the sample when isolated from the ambient g-jitter; this resulted in markedly increased solute transport. To further explore the effects arising in these long capillary diffusion couples from the absence of unit-gravity and the presence of the forced g-jitter, the effects of a 1 milli-g forcing vibration on the mass transport in a 1.5 mm diameter long capillary diffusion couple have been simulated. In addition, to increase understanding of the role of unit gravity in determining the extent to which gravity can influence measured diffusion coefficient values, comparative experiments involving gold, silver, and antimony diffusing in liquid lead have been carried out using a similar QUELD II facility to that employed in the QUELD II/MIM/MIR campaign but under terrestrial conditions. It was found that buoyancy-driven convection may still persist in the liquid even when conditions are arranged for a continuously decreasing density gradient up the axis of a vertical long capillary diffusion couple due to the presence of small radial temperature gradients.

The influence of Marangoni flows on crack growth in cast metals.

In previous work with copper-based alloys, the authors showed that a necessary part of the hot-tearing process is the creation of a void in association with an inclusion and its subsequent growth to form the crack observed in the as-cast state. The work reported here is an examination of hot tearing in aluminum alloy A201 and various similar Al-based aerospace alloys to determine (1) if a similar process to that seen in copper alloys takes place; (2) the extent to which buoyancy forces influence the movement of solute-enriched liquid and so contribute to the development of voids which are subsequently observed as hot tears; and (3) the influence of the local variations in liquid/void surface tension arising due to local composition and temperature changes on interdendritic fluid flow--that is, the effects of Marangoni convection on void size and movement during solidification. Hot cracking of aluminum alloy A201 has been examined under standardized experimental conditions. In addition, experiments were conducted in which fluid flow in test castings was controlled by magnetic fields. The results from these various investigations are presented in this paper. Similar experiments are planned for reduced gravity aircraft parabolic flights. To assist in the planning and interpretation of the results, numerical modeling simulations have been developed for Al-Cu alloys.

Early postoperative feeding after elective colorectal surgery.

BACKGROUND: Several investigators have demonstrated that routine nasogastric decompression after abdominal surgery is unnecessary and can be safely eliminated, and 1 recent study demonstrated the safety of early oral feedings. OBJECTIVE: To test the hypothesis that successful early feeding would lead to a shorter duration of hospitalization and, therefore, would be more cost-effective. PATIENTS: Fifty-eight patients with elective colorectal surgery. METHODS: Patients were prospectively randomized to 1 of 2 postoperative treatment arms: early feeding (EF group, n = 29) and traditional feeding (TF group, n = 29). All patients in the EF group began a liquid diet on the first postoperative day and were advanced to a regular diet when they consumed 1000 mL in 24 hours. All patients in the TF group began a liquid diet after resolution of the postoperative ileus and were advanced to a regular diet after consuming 1000 mL in 24 hours. Patients were dismissed after tolerating two thirds of the regular diet. Both groups had intraoperative orogastric tubes that were removed at the end of surgery. Nasogastric tubes were inserted for persistent postoperative vomiting. RESULTS: No significant differences were noted in age, types of procedures, or in prior abdominal surgery in either group. No significant differences were seen in rates of nausea (55% in EF vs 50% in TF group) or vomiting (48% in EF vs 33% in TF group). One patient in the EF group had aspiration pneumonia, and anastomotic leak resulted in sepsis and eventual death of 1 patient in the TF group. No significant difference was observed in length of hospital stay between the 2 groups (mean +/- SD, 7.2 +/- 3.3 days in EF vs 8.1 +/- 2.3 days in TF group). CONCLUSIONS: Early oral feeding after elective colorectal surgery is safe. Most of the patients tolerated EF; however, there was no significant difference in duration of hospitalization in these patients.

Computed tomography and ultrasonography in the diagnosis of appendicitis: when are they indicated?

HYPOTHESIS: Relative merits and indications exist for ultrasonography (US) and computed tomography (CT) in the diagnosis of appendicitis. DESIGN: Prospective study. SETTING: General community and tertiary care hospital. METHODS: Ninety-nine patients (50 males and 49 females) were studied. Following consent, the initial disposition was recorded, designating the patient for operation, observation, or discharge from the hospital. Each patient was studied by CT and US. Studies were independently evaluated by 2 radiologists, and the results were designated as positive, negative, or equivocal. The surgeon reevaluated patients before and after learning the results of US and CT, recording whether the CT scan, US, or reexamination influenced the final disposition. RESULTS: Fifty patients had appendicitis; 6 appendixes were perforated. The initial clinical impression called for 44 operations, 49 observations, and 6 discharges. Thirty-four patients had their treatment plan changed from the initial disposition. Ultrasonography did not affect the initial impression. In contrast, 18 patients were rediagnosed solely on CT scan findings. Seven patients were rediagnosed by reexamination. Of 44 patients initially designated for operation, the CT scan and reexamination spared 6 females from surgery; the negative appendectomy rate potentially decreased from 50% to 17% (P =.03). The CT scan, US, or reexamination failed to spare 2 males from exploration with negative results. Of the 49 patients initially designated for observation, 23 were rediagnosed after reevaluation, 13 were discharged from the hospital, and 10 underwent expedient operation. One patient was spared from inappropriate discharge from the hospital. The reliability of the CT scan was good, with high sensitivities and specificities. Equivocal scan results lowered the diagnostic value. CONCLUSIONS: Selective use of a CT scan with a second examination can improve the diagnostic accuracy and management of suspected cases of appendicitis by (a) reducing the negative appendectomy rate in females, (b) moving patients from observation to earlier operation or discharge from the hospital, and (c) preventing inappropriate discharge of patients with appendicitis.

Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells.

Aqueous extracts of the brains of 18-day-old white Leghorn chicken embryos contain several substances that stimulate proliferation of primary cultures of chick brain astrocytes. Most of the mitogens are peptides. Purification of one mitogenic fraction was obtained by centrifugation, passage through Amicon Diaflo membranes of nominal molecular weight cutoffs 30, 1 and 0.5 kDa, ion exchange chromatography and reverse phase high performance liquid chromatography (HPLC) using a Deltapak C18 column. The mitogenic fraction contained no amino acids. On the basis of its behaviour on thin layer chromatography, its ultraviolet absorption spectrum, its 1H and 31P nuclear magnetic resonance spectra and its behaviour on positive and negative ion fast atom bombardment mass spectrometry, the mitogenic material was identified as adenosine-5'-monophosphate (AMP). Other adenosine compounds including adenosine, ADP and ATP also stimulated proliferation of and [3H]leucine incorporation into primary cultures of astrocytes. Nitrobenzylthyioinosine (NBTI), an inhibitor of nucleoside transport, did not prevent the stimulation of [3H]leucine incorporation into cultured astrocytes. Polyadenylic acid (Poly A), that mimics the effect of adenosine at adenosine receptors, also stimulated proliferation of the astrocytes. The effects of adenosine and Poly A were not inhibited by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) but were inhibited by 1,3-dipropyl-7-methyl-xanthine (DPMX), indicating that adenosine and Poly A acted at the cell surface, likely through adenosine A2 receptors. The stimulatory effect of ATP was biphasic. The proliferative effect of low, but not of high, concentrations of ATP were abolished by DPMX. The purinergic P2 receptor agonist 2-methylthioATP and, at higher concentrations, the P2y agonist, alpha,beta-methyleneATP also stimulated incorporation of [3H]thymidine. These data indicate that high concentrations of ATP stimulate cell proliferation through at a P2, possibly a P2y receptor. These results have considerable biological significance. After brain injury, or when cells in brain die or become hypoxic, nucleotides and nucleosides are released from the cells. Their extracellular concentrations can exceed those required to stimulate astrocyte proliferation in vitro. Therefore they may be partly responsible for gliotic changes following cell death in brain.

Allergic hypersensitivity to neomycin. Relationship between patch test reactions and 'use' tests.

The prevalence of neomycin patch test sensitivity in the general population is approximately 1%. We describe the relationship between positive neomycin patch tests and clinical "use tests" with two antibiotic combinations (Neosporin G cream and Neosporin ointment). The neomycin use test was positive in seven of eight subjects with a strongly positive patch test, and in two of four subjects with a weakly positive patch test. A positive use test usually occurred earlier and was always more intense with the cream base. The use test reactions were usually mild even with continued application of the antigen. Use tests with commercial products may be helpful in evaluating the clinical relevance of positive patch tests.

Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population.

A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population.