bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in renal hemodynamics and urodynamics in rats with chronic hyperoxaluria and after acute oxalate infusion: Role of free radicals
Authors: Huang Ho‐Shiang , Ma Ming‐Chieh , Chen Jun , Chen Chau‐Fong
Published: February 2003

Aims

The aim of this study was to evaluate possible changes in renal hemodynamic and urodynamic parameters in rats with chronic hyperoxaluria and after acute oxalate challenge. We also evaluated the possible association between free radical (FR) production, hyperoxaluria, and calcium oxalate (CaOx) calculi formation.

Methods

Chronic hyperoxaluria was induced by adding 0.75% ethylene glycol (EG) to the drinking water of male Wistar rats. After 7, 21, and 42 days of treatment, urinary biochemistry, oxalate levels, and lipid peroxides were measured. Kidney calculi were examined by polarizing microscopy. In the second part of the experiments, 1, 10, 20, and 30 mg kg−1 hr−1 oxalate was infused, by means of an intrarenal arterial catheter (IRA), into normal rats sequentially. Superoxide dismutase (SOD) infusion by means of IRA, in addition to oxalate, was also performed to check its influence on the altered renal function after oxalate infusion. In both the acute and chronic groups, renal blood flow (RBF), cortical microvascular blood flow (CMVBF), glomerular filtration rate (GFR), urine flow (UV), and urinary sodium excretion (UNaV) were measured, and chemiluminescence (CL) was examined in the renal venous blood.

Results

Levels of urinary lipid peroxides and enzymuria had increased since day 7, and increased the size of numbers of CaOx crystals in the kidney were noted beginning on day 21, but elevated CL was detectable only on day 7 after 0.75% EG treatment. Decreased UV and UNaV were noted in the 42‐day EG group, although the 24‐hr creatinine clearance values were normal in all experimental groups. On the other hand, RBF, GFR, and CMVBF were attenuated with elevated FR when the oxalate concentration was higher than 10 mg kg−1 hr−1 in the acute oxalate infusion group. With SOD pretreatment, the decreased RBF, GFR, and CMVBF could be reversed at 10 mg kg−1 hr−1 of oxalate, and be partially reversed at 20. FR also could be reduced significantly at 10 and 20 mg kg−1 hr−1 of oxalate.

Conclusions

Decreased urine flow and sodium excretion were the main renal functions affected by chronic hyperoxaluria. However, that only the 42‐day EG group had a decreased tubular function cannot be fully explained by the persistent tubular enzymuria and increased lipid peroxides that began on day 7 after EG treatment. With acute oxalate infusion, the major insult to renal function was renal hemodynamics. Pretreated SOD could reverse the attenuated hemodynamics and reduce the elevated FR partly, which suggested that FR is responsible for oxalate toxicity. Neurourol. Urodynam. 22:176–182, 2003. © 2003 Wiley‐Liss, Inc.
Science after Stalin: Forging a New Image of Soviet Science
Authors: Ivanov Konstantin
Published: February 2003

Argument

Post-Stalinist reforms resulted in dramatic changes in the ways of operation of Soviet science: one can say that they altered the very understanding of what science was, or should be, in the socialist society. A new vision came about as a result of political and rhetorical efforts of scientists, who pushed forward their various, often conflicting, agendas acting in accordance with specific rules of Soviet polity. The most visible part of the reform came with the 1961 administrative reorganization of the USSR Academy of Sciences. The related series of changes, however, was much broader and comprehensive, modifying the relationships between science and ideology, politicians and academic researchers, and establishing the very division between fundamental and applied research, which had been strongly rejected during the preceding Stalinist period.
Expression of Constitutive but not Inducible Cyclooxygenase Maintains Articular Perfusion in the Rat Knee
Authors: Egan Colin G. , Lockhart John C. , McLean John S. , Ferrell William R.
Published: February 2003

Experiments were performed in the normal rat knee joint to investigate the role of different isoforms of cyclooxygenase (COX) in the regulation of basal joint blood flow. Laser Doppler imaging (LDI) was used to measure articular perfusion, and reverse transcriptase polymerase chain reaction (RT‐PCR) for the detection of COX‐1 and COX‐2 mRNA in joint tissue. Intravenous infusion of indomethacin (a non‐selective inhibitor of COX; 0.34 nmol min−1) over 40 min produced a time dependent increase in articular vascular resistance (maximum 22.5% at 40 min; P < 0.0001, one‐way ANOVA) whereas vehicle over a similar time period had no effect in a control group. An equimolar concentration of a highly selective inhibitor for COX‐2, SC‐236, was administered in a further group of rats but this did not increase articular vascular resistance. While there was no significant difference between the response to vehicle and SC‐236 (two‐way ANOVA; P= 0.686, n= 6) the response to indomethacin was significantly greater than vehicle or SC‐236 (two‐way Anova; P < 0.0001, n= 6). COX‐1, but not COX‐2, was detectable by RT‐PCR in all joint tissue samples examined (n= 4). The results of this study indicate that prostaglandins (PGs) play an important role in the maintenance of basal perfusion in the rat knee joint, with COX‐1 being the physiologically relevant isoform.
Eccentric Contractions Affect Muscle Membrane Phospholipid Fatty Acid Composition in Rats
Authors: Helge J. W. , Therkildsen K. J. , Jørgensen T. B. , Wu B. J. , Storlien L. H. , Asp S.
Published: February 2003

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty‐three rats were randomised to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n‐6 (17.7 ± 0.6; 16.4 ± 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n‐3 (2.9 ± 0.1 and 2.7 ± 0.1% of total fatty acids, respectively) was uniformly higher across groups (P < 0.02) with no differences between diet groups. The proportion of long chain polyunsaturates was also significantly higher in the eccentrically contracted (39.9 ± 0.6% of total fatty acids) compared to the control leg (38.2 ± 0.6% of total fatty acids; P < 0.01). In contrast no differences were observed in the fatty acid composition of the triacylglycerols stored within the muscle. Thus one severe bout of eccentric contractions modulates the fatty acid composition of the muscle membrane phospholipids when compared to a control leg, and supplemental intake of fish oil or vitamin C did not attenuate this effect.
Effects of Pinealectomy on Glucagon Responsiveness to Hypoglycaemia Induced by Insulin Injections in Fed Rats
Authors: Kosa Erzsebet , Maurel Daniel , Siaud Philippe
Published: February 2003

The glucagon response to insulin‐induced hypoglycaemia was tested in rats that had been pinealectomised (Px), pinealectomised and fitted with melatonin implants (Px + MLT), or sham‐operated (SO). The glucagon response to hypoglycaemia observed in SO rats (216 ± 27 pg ml−1 at baseline versus 397 ± 35 pg ml−1 at the hypoglycaemic peak, mean ± S.D.) was stronger than that in Px rats (180 ± 37 pg ml−1 and 229 ± 21 pg ml−1, respectively) and weaker than that in Px + MLT rats (256 ± 19 pg ml−1 and 516 ± 11 pg ml−1, respectively). Our data indicate that the capacity to release glucagon during insulin‐induced hypoglycaemia is altered in pinealectomised rats.
Differential Effects of Cold Exposure on Muscle Fibre Composition and Capillary Supply in Hibernator and Non‐Hibernator Rodents
Authors: Egginton S. , Fairney J. , Bratcher J.
Published: February 2003

Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8‐10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light‐23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross‐sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm−2, N; 201 ± 12 mm‐2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30% smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm−2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 μm2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 μm2, N; 846 μm2, H; n.s.) but a marked reduction in the core (871 μm2, N; 604 μm2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy.
Interleukin‐1β‐Induced Fever Does not Alter the Ability of 5‐ to 6‐Day‐Old Rat Pups to Autoresuscitate from Hypoxia‐Induced Apnoea
Authors: Fewell James E. , Wong Vanessa H.
Published: February 2003

Experiments were carried out to determine if endogenous pyrogen‐induced fever impairs protective responses of newborn rats to hypoxia. Twenty‐seven 5‐ to 6‐day‐old conscious rat pups received a subcutaneous injection of 0.20 μg of recombinant rat interleukin‐1β (rrIL‐1β) per kilogram of body weight to induce fever, or an equal volume of vehicle. They were then either exposed to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N2‐3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnoea was determined. Core temperature increased significantly following administration of rrIL‐1β but did not change following administration of vehicle (i.e. vehicle, 0.0 ± 0.1 °C; rrIL‐1β, 0.7 ± 0.3 °C; P < 0.001) before exposure to hypoxia. IL‐1β‐induced fever did not alter the time to last gasp when the pups were exposed to a single period of hypoxia or the number of successful autoresuscitations upon repeated exposure to hypoxia. Thus, our data do not support the hypothesis that endogenous pyrogen‐induced fever impairs the protective responses in newborns that may prevent death during hypoxia as may occur during single or repeated episodes of prolonged sleep apnoea.
Myocardial Response to Incremental Exercise in Endurance‐Trained Athletes: Influence of Heart Rate, Contractility and the Frank‐Starling Effect
Authors: Warburton Darren E. R. , Haykowsky Mark J. , Quinney H. Arthur , Blackmore Derrick , Teo Koon K. , Humen Dennis P.
Published: February 2003

Recent evidence indicates that endurance‐trained athletes are able to increase their stroke volume (SV) throughout incremental upright exercise, probably due to a progressively greater effect of the Frank‐Starling mechanism. This is contrary to the widely held belief that SV reaches a plateau at a submaximal heart rate (irrespective of fitness level), owing to a limitation in the time for diastolic filling. The purpose of this investigation was to evaluate whether endurance‐trained athletes rely on a progressively greater effect of the Frank‐Starling mechanism throughout incremental exercise. A secondary purpose was to evaluate the effects of postural position on the cardiovascular responses to incremental exercise. Ten male cyclists participated in this investigation. Left ventricular function was assessed throughout incremental exercise in the supine and upright positions (counterbalanced) using radionuclide ventriculography. Stroke volume increased in a linear fashion during incremental exercise in both the upright and supine positions. The increases in cardiac output (Q) throughout incremental to maximal exercise (in both the supine and upright positions) were significantly related to changes in heart rate, myocardial contractility and the Frank‐Starling mechanism. Percentage changes in end‐diastolic volume and SV were significantly greater in the upright position versus the supine position, reflecting an increased reliance on the Frank‐Starling effect to increase Q. We conclude from this investigation that highly trained endurance athletes are able to make progressively increasing usage of the Frank‐Starling effect throughout incremental exercise. Postural position has a significant effect on the relative contribution of heart rate, myocardial contractility and the Frank‐Starling mechanism to the increase in Q during exercise conditions.
Fatigue‐Induced Change in Corticospinal Drive to Back Muscles in Elite Rowers
Authors: Fulton Rick C. , Strutton Paul H. , McGregor Alison H. , Davey Nick J.
Published: February 2003

This study examined post‐exercise changes in corticospinal excitability in five ‘elite’ rowers and six non‐rowers. Transcranial magnetic stimulation (TMS) was delivered to the motor cortex and bilateral electromyographic (EMG) recordings were made from erector spinae (ES) muscles at L3/L4 spinal level and from the first dorsal interosseous (FDI) muscle of the dominant hand. Each subject completed two exercise protocols on a rowing ergometer: a light exercise protocol at a sub‐maximal output for 10 min and an intense exercise protocol at maximum output for 1 min. A trial of ten magnetic stimuli was delivered before each of the protocols and, on finishing exercise, further trials of ten stimuli were delivered every 2 min for a 16 min period. Amplitudes of motor‐evoked potentials (MEPs) in each of the three test muscles were measured before exercise and during the recovery period after exercise. The non‐rowers showed a brief facilitation of MEPs in ES 2 min after light and intense exercise that was only present in the elite rowers after intense exercise. In the period 4‐16 min after light exercise, the mean (± S.E.M.) MEP amplitude (relative to pre‐exercise levels) was less depressed in the elite rowers (79.4 ± 2.1%) than in the non‐rowers (60.9 ± 2.5%) in the left ES but not significantly so in the right ES. MEP amplitudes in FDI were significantly larger in the elite rowers, averaging 119.0 ± 3.1% pre‐exercise levels, compared with 101.2 ± 5.8% in the non‐rowers. Pre‐exercise MEP latencies were no different in the two groups. After light exercise MEP latencies became longer in the elite rowers (left ES, 16.1 ± 0.5 ms; right ES, 16.1 ± 0.4 ms; dominant FDI, 23.4 ± 0.2 ms) than in the non‐rowers (left ES, 15.0 ± 0.3 ms; right ES, 15.2 ± 0.3 ms; dominant FDI, 21.5 ± 0.2 ms). There were no differences in MEP depression or latency between elite rowers and non‐rowers after intense exercise. We conclude that the smaller degree of MEP depression in the elite rowers after light exercise reflects less central fatigue within corticospinal control pathways than that seen in the non‐rowers. The longer latency of MEPs seen in the elite rowers may reflect recruitment of more slower‐conducting fatigue‐resistant motor units compared with the non‐rowers. These differences may be because the energy requirements for the non‐rowers during light exercise are closer to their maximum capacity, leading to more fatigue. This notion is supported by the lack of any difference between groups following intense exercise when both groups were working at their own maximum.
Regulation and Co‐Ordination of Nuclear Gene Expression During Mitochondrial Biogenesis
Authors: Goffart S. , Wiesner R. J.
Published: February 2003

Biogenesis of mitochondria is happening constantly due to the physiological and developmental situation of a cell. As mitochondrial biogenesis is a complex process producing about 20 % of cellular protein, the expression of the 1000 genes involved is expected to be coordinated and regulated tightly. The variety of physiological stimuli and differentiation states lead to the idea of a complex network connecting many different regulatory pathways. By analysing nuclear encoded mitochondrial genes some of the factors involved in the regulation and coordination of mitochondrial gene expression were identified. These factors include general transcription factors such as Sp1 or YY1, as well as transcription factors specific for mitochondrial genes like the nuclear respiratory factors NRF1 and 2. An important control function linked to the physiological situation of a cell is triggered by hormones such as steroid and thyroid hormones. Even cell type‐specific regulatory proteins like the myogenin transcription factor family have a strong influence on some mitochondrial genes in the specific cellular background. The regulatory function of most of these proteins can be modulated and enhanced by the coactivators PGC‐1α and β and PRC. Although regulatory pathways have been characterized in more detail in recent years, no regulation mechanism has been shown to work on all analysed mitochondrial genes, and the general concept of mitochondrial regulation still remains unclear.
Overproduction of Polypeptides Corresponding to the Amino Terminus of the F-Box Proteins Cdc4p and Met30p Inhibits Ubiquitin Ligase Activities of Their SCF Complexes
Authors: Dixon Cheryl , Brunson Lee Ellen , Roy Mary Margaret , Smothers Dechelle , Sehorn Michael G. , Mathias Neal
Published: February 2003

Ubiquitin ligases direct the transfer of ubiquitin onto substrate proteins and thus target the substrate for proteasome-dependent degradation. SCF complexes are a family of ubiquitin ligases composed of a common core of components and a variable component called an F-box protein that defines substrate specificity. Distinct SCF complexes, defined by a particular F-box protein, target different substrate proteins for degradation. Although a few have been identified to be involved in important biological pathways, such as the cell division cycle and coordinating cellular responses to changes in environmental conditions, the role of the overwhelming majority of F-box proteins is not clear. Creating inhibitors that will block the in vivo activities of specific SCF ubiquitin ligases may provide identification of substrates of these uncharacterized F-box proteins. Using
Saccharomyces cerevisiae
as a model system, we demonstrate that overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p results in specific inhibition of their SCF complexes. Analyses of mutant amino-terminal alleles demonstrate that the interaction of these polypeptides with their full-length counterparts is an important step in the inhibitory process. These results suggest a common means to inhibit specific SCF complexes in vivo.
The Inadvertent Conception and Late Birth of the Free-Will Problem
Authors: Bobzien Susanne
Published: February 2003

In this paper I argue that the "discovery" of the problem of causal determinism and freedom of decision in Greek philosophy is the result of a mix-up of Aristotelian and Stoic thought in later antiquity; more precisely, a (mis-)interpretation of Aristotle's philosophy of deliberate choice and action in the light of Stoic theory of determinism and moral responsibility. The (con-)fusion originates with the beginnings of Aristotle scholarship, at the latest in the early 2nd century A.D. It undergoes several developments, absorbing Epictetan, Middle-Platonist, and Peripatetic ideas; and it leads eventually to a concept of freedom of decision and an exposition of the "free-will problem" in Alexander of Aphrodisias' On Fate and in the Mantissa ascribed to him.
MsGC-β3 forms active homodimers and inactive heterodimers with NO-sensitive soluble guanylyl cyclase subunits
Authors: Morton David B. , Anderson Esther J.
Published: February 2003

Soluble guanylyl cyclases are typically obligate heterodimers, composed of a single alpha and a single beta subunit. MsGC-β3, identified in the tobacco hornworm Manduca sexta, was the first example of a soluble guanylyl cyclase that exhibited enzyme activity without the need for coexpression with additional subunits. Subsequent studies have revealed that the mammalian β2 subunit also shares this property. Using a combination of gel filtration chromatography, coprecipitation and site-directed mutagenesis we show that, as predicted, MsGC-β3 forms active homodimers. We also demonstrate that MsGC-β3 is capable of forming heterodimers with the nitric oxide (NO)-sensitive guanylyl cyclase subunits MsGC-α1 and MsGC-β1. These heterodimers, however, show no enzyme activity and, like mammalian β2 subunits, act in a dominant negative manner when combined with the NO-sensitive subunits to disrupt their activation by NO. In addition,we show that the unique C-terminal domain of MsGC-β3 is not necessary for enzyme activity and might act as an auto-inhibitory domain.
Nondestructive FTIR monitoring of leaf senescence and elicitin‐induced changes in plant leaves
Authors: Ivanova Diana G. , Singh Bal Ram
Published: February 2003

The applicability of the FTIR attenuated total reflectance technique for in situ monitoring of plant physiological processes such as leaf senescence and aging has been examined. Difference spectra obtained by subtracting the spectrum of the young plant leaf from that of the older one revealed positive bands at 1650–1500 cm−1, indicating a higher relative concentration of phenolics in the older leaves of both black cherry and sweet pepper bush leaves. Prolonged physiological stress of tobacco leaves exhibited a progressive time‐dependent increase of the absorbance at around 3475 cm−1, corresponding to hydroxyl functional groups. Absorption changes were also observed between 1650 and 1500 cm−1, which are likely to correspond to phenolics. The characteristic changes of the FTIR absorbance spectra resulting from physiological and induced aging were detected also as a response to treatment with a recombinant α‐elicitin, cinnamomin. This allowed the first quantification of the biological activity of a recombinant elicitin using a spectroscopic method. We suggest that FTIR spectroscopy provides important information about physiological events occurring in plant tissue in vivo, and it could be useful for the in situ characterization of the plant responsiveness to fungal toxins such as elicitins. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 79–85, 2003
1H‐NMR and 13C‐NMR lipid profiles of human renal tissues
Authors: Tugnoli V. , Bottura G. , Fini G. , Reggiani A. , Tinti A. , Trinchero A. , Tosi M. R.
Published: February 2003

Lipids from human renal tissues are studied by means of 1H‐ and 13C‐NMR spectroscopy. The total lipid fractions obtained from healthy kidneys, malignant renal cell carcinomas, and benign oncocytomas are characterized and analyzed to elucidate the main differences between the functional and neoplastic tissues. In all cases the lipid components are well identified. The healthy kidney is characterized by high amounts of triglycerides and the presence of cholesterol in its free form. On the contrary, renal cell carcinomas contain high amounts of cholesterol that are almost completely esterified as oleate, suggesting an intracellular localization of the cholesteryl esters synthesis. Cholesteryl esters are considered markers of renal cell carcinomas, thus supporting recent theories that these compounds play a leading role in cell proliferation. Oncocytomas are particularly rich in phosphatidylcholine and, analogous to the healthy kidney, are completely lacking in cholesteryl esters. Healthy kidneys and oncocytomas appear to have other similarities if compared with renal cell carcinomas: a very high fatty acyl/cholesterol ratio, the presence of dolichols, and a higher grade of unsaturation. The 13C data suggest a new method for the direct evaluation of the saturated/unsaturated fatty acyl ratio. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 86–95, 2003
Evidence that direct DNA uptake through cut shoots leads to genetic transformation of Solanum aviculare Forst
Authors: Gahan P. B. , Wyndaele R. , Mantell S. , Boggetti B.
Published: February 2003

The reporter genes GUS, NPTII and BAR, either separately or in combination, have been exploited to determine if DNA which can directly enter plants, circulate within the plant and enter nuclei, can also integrate into the genome in a manner which will permit gene expression. Feeding of either seed‐derived or adventitious cut shoots of Solanum aviculare with the GUS gene followed by rooting of the shoots and growing on, resulted in all tissues of the plant showing GUS activity as detected cytochemically. Southern blot analysis of plants derived from the adventitious shoots confirmed the presence of the reporter gene in roots. Reporter gene expression was observed also in the F1 generation. If GUS and NPTII or GUS, NPTII and BAR were fed together, then in each case it was possible to have both expression and Southern blot confirmation of each of the genes. There was a relatively high rate of transformation of approximately 5% of the fed stems across all experiments conducted during the present study. Copyright © 2002 John Wiley & Sons, Ltd.
On the role of chiral catalysts in the alkenyl zirconocene/zinc addition to aldehydes: A study of ligand loading and asymmetric amplification
Authors: Wipf Peter , Jayasuriya Nilukshi , Ribe Seth
Published: February 2003

Unusual nonlinear asymmetric amplification and chiral ligand loading effects were discovered for the use of catalytic quantities of chiral aminoalcohols in the in situ hydrozirconation—transmetalation—aldehyde addition processes. While the stereochemically most efficient aminothiol ligands demonstrated mechanistically conventional reaction parameters in excellent agreement with Kagan's ML2 system, the asymmetric induction in the presence of a chiral aminoalcohol was found to vary greatly with loading and %ee of the ligand. Aminothiols remain the ligands of choice for the highly enantioselective formation of allylic alcohols and provide experimentally more predictable reaction variables. However, new, optimized conditions lead to a synthetically useful product %ee using the readily available and scalable aminoalcohol 2a. Chirality 15:208–212, 2003. © 2003 Wiley‐Liss, Inc.
Lipase regio‐ and stereoselectivities toward three enantiomeric pairs of didecanoyl‐deoxyamino‐O methyl glycerol: A kinetic study by the monomolecular film technique
Authors: Douchet Isabelle , de Haas Gerard , Verger Robert
Published: February 2003

A kinetic study was carried out on the regio‐ and stereoselectivities of 12 lipases of animal and microbial origin. For this purpose, monomolecular films consisting of three pairs of enantiomers (didecanoyl‐deoxyamino‐O methyl glycerol, DDG) containing a single hydrolyzable decanoyl ester bond and two lipase‐resistant groups were spread at the air–water interface. Each of the lipases tested displayed a particular type of behavior, on the basis of which they were classified in two groups, depending on their ability to hydrolyze the sn‐2 position. From the qualitative point of view, the sn‐2 preference measured on triacylglycerides and DDG were in good agreement. The inductive chemical effect might explain why a greater level of hydrolytic activity was observed with the diglycerides than with DDG. With most of the lipases tested, it was observed that the enantiomeric pair having two distal acyl chains was more clearly differentiated stereochemically than the two homologous pairs with two adjacent acyl chains. This finding is consistent with the hypothesis that during the chiral recognition process two of the three attachment points may be the external (distal) hydrophobic chains, which is in line with the hypothesis of a tuning fork conformation of a triglyceride in the lipase active site. Chirality 15:220–226, 2003. © 2003 Wiley‐Liss, Inc.
Water‐borne, in situ crosslinked biomaterials from phase‐segregated precursors
Authors: Vernon Brent , Tirelli Nicola , Bächi Thomas , Haldimann David , Hubbell Jeffrey A.
Published: February 2003

A novel process for the preparation of water‐borne biomaterials for hard tissue repair from injectable precursors is described, where the precursors form crosslinked materials in situ under physiological conditions. The precursors react by means of a Michael‐type addition reaction that makes use of addition donors such as pentaerythritol tetrakis 3′‐mercaptopropionate (QT) and addition acceptors such as poly(ethylene glycol) diacrylate 570 MW (PEGDA), pentaerythritol triacrylate (TA), and poly(propylene glycol) diacrylate 900 MW (PPODA). These crosslinked materials (at 75 wt% solid), prepared from water dispersions or reverse emulsions, showed ultimate strengths in compression of 1.8 ± 0.2 and 6.7 ± 0.5 MPa and ultimate deformations of 35 ± 2± and 37 ± 2%, respectively. Scanning electron microscopy (SEM) shows that the morphology of the precursors templated the morphology of the final materials. The current study indicates that it is possible to obtain injectable high‐modulus materials that have appropriate mechanical properties and gelation kinetics for tissue augmentation and stabilization applications such as mechanical stabilization of the intervertebral disc annulus. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 447–456, 2003
Bond strength, compositional, and structural properties of hydroxyapatite coating on Ti, ZrO2‐coated Ti, and TPS‐coated Ti substrate
Authors: Yang Yunzhi , Ong Joo L.
Published: February 2003

The effect of titanium plasma‐sprayed (TPS) and zirconia (ZrO2)‐coated titanium (Ti) substrates on the adhesive, compositional, and structural properties of plasma‐sprayed hydroxyapatite (HA) coatings were evaluated. X‐ray diffraction, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, surface roughness, and adhesive strength were used to characterize the coatings. Apatite‐type and α‐tricalcium phosphate phases were observed for all HA coatings. A structural change due to the absence of a 960 cm−1 peak during FTIR analysis was observed for all HA coatings. The coating surfaces appeared rough and melted, with surface roughness correlating to the size of the starting powder. No significant difference in the Ca/P ratio of HA on Ti and TPS‐coated Ti substrates was observed. However, the Ca/P ratio of HA on ZrO2‐coated Ti substrate was significantly increased. Interfaces between all coatings and substrates were observed to be dense and tightly bound, except for HA coatings on TPS‐coated Ti substrate interface. However, an intermediate TPS or ZrO2 layer between the HA and Ti substrate resulted in a lower adhesive strength as compared to HA on Ti substrate. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 509–516, 2003
Reserving resilient capacity for a single commodity with upper‐bound constraints
Authors: Brightwell G. , Oriolo G. , Shepherd F. B.
Published: February 2003

Continuing research begun in a previous study [SIAM J Discr Math 14 (2001), 524–539], we investigate problems of reserving capacity in the arcs of a network, subject to the constraint that, on the failure of any one arc, there is enough reserved capacity on the remaining arcs to support a flow of value T from a source s to a destination t. We also impose upper bounds on the amount of capacity we may reserve on the arcs: This alters the nature of the problem. In the case where each arc has the same upper bound, we investigate the strategy of finding the minimum‐cost reservation that is itself an acyclic (s, t) flow: We show that such a reservation is easy to find, always has a simple form, and has a cost at most twice that of the optimal solution. In the case where each arc has its own upper bound, we explain why no such results can hold, but we do give an efficient algorithm for the case where we are asked for a reservation on a fixed set of arc‐disjoint paths. We consider the case where we are free to reserve on each arc as much capacity as we want but only in bundles of fixed size. © 2003 Wiley Periodicals, Inc.
Robustness properties of multivariate EWMA control charts
Authors: Testik Murat C. , Runger George C. , Borror Connie M.
Published: February 2003

In this paper, the robustness of the multivariate exponentially weighted moving average (MEWMA) control chart to non‐normal data is examined. Two non‐normal distributions of interest are the multivariate $t$ distribution and the multivariate gamma distribution. Recommendations for constructing MEWMA control charts when the normality assumption may be violated are provided. Copyright © 2002 John Wiley & Sons, Ltd.
Microscopic mechanism for C60 superconductivity
Authors: March Norman H. , Squire R. H.
Published: February 2003

After a brief discussion of the four classes of superconducting materials, attention is focused on the fullerides. More critically, motivated by the work of Herzberg and Longuet‐Higgins (HLH), especially in the context of the Berry phase, and the topological superconducting model of Wiegmann we propose a microscopic model of C60 superconductivity. One key is the relationship of the HLH phase sign change of the wave function circling a degeneracy. The sign change is related to a topological quantity, a Chern number, which is a requirement specified for a topological superconductor, following Weigmann. Thus, it seems vibrational modes are topologically and coherently coupled to the electronic wave function. We establish a microscopic basis for topological superconductivity using Weigmann's generalization of Fröhlich's 1‐D model to two dimensions. This necessarily invokes the nonlinear sigma model and the addition of topological terms. We then reinterpret the work of Auerbach et al. and O'Brien by suggesting that vibrational analysis of C60 with Jahn–Teller distortions that produce a collective mode(s) that could be described by a soliton or, equivalently, a skyrmion model. The soliton (skyrmion) statistics are such that both fermions and bosons result depending on the number of electrons, n. Superconductivity is predicted for n = 3, and possibly 5 electrons, and n = 2 and 4 should be insulators. The strong coupling theory developed seems appropriate for describing a molecular superconductor. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Multidimensional analysis system for quantitative chemistry problems: Symbol, macro, micro, and process aspects
Authors: Dori Yehudit J. , Hameiri Mira
Published: February 2003

There is a consensus regarding the fact that students encounter difficulties in understanding scientific concepts, such as the particulate nature of matter, the mole, and the interpretation of chemical symbols. Researchers and practitioners have been looking for teaching methods to improve students' understanding of quantitative chemistry and their ability to solve related problems. This study describes the Multidimensional Analysis System (MAS), an approach to constructing, classifying, and analyzing quantitative chemistry problems. MAS enables classification based on complexity and transformation levels of a quantitative problem. We define three transformation levels: symbol ↔ macro, symbol ↔ micro, and symbol ↔ process. Applying this framework to teaching and research, we investigated the relationships between MAS‐classified chemistry problems and student achievement in solving these problems. The research population, 241 high school chemistry students, studied problem solving according to MAS for 9 weeks; the control group studied the same topic for the same duration in the traditional way. Student achievement was sorted by mathematics level and gender. We found that the success rate of the entire student population in solving these problems decreased as the problem difficulty increased. Experimental group students scored significantly higher than their control group peers. The improvement in student achievement was significantly dependent on the pretest score and the mathematics level, and independent of gender. Students who studied mathematics in the basic level benefited significantly more from MAS‐based teaching than their peers, whose mathematics level was advanced. Based on the research findings, we recommend applying the multidimensional analysis approach while teaching quantitative problems in chemistry. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 40: 278–302, 2003
The Great War, the Russian Civil War, and the Invention of Big Science
Authors: Kojevnikov Alexei
Published: February 2003

Argument

The revolutionary transformation in Russian science toward the Soviet model of research started even before the revolution of 1917. It was triggered by the crisis of World War I, in response to which Russian academics proposed radical changes in the goals and infrastructure of the country’s scientific effort. Their drafts envisioned the recognition of science as a profession separate from teaching, the creation of research institutes, and the turn toward practical, applied research linked to the military and industrial needs of the nation. The political revolution and especially the Bolshevik government that shared or appropriated many of the same views on science, helped these reforms materialize during the subsequent Civil War. By 1921, the foundation of a novel system of research and development became established, which in its most essential characteristics was similar to the U.S. later phenomenon known as “big science.”
Transfer of metformin into human milk
Authors: Gardiner Sharon J. , Kirkpatrick Carl M.J. , Begg Evan J. , Zhang Mei , Moore M.Peter , Saville Dorothy J.
Published: February 2003

Objectives

Our objectives were to determine the milk‐to‐plasma ratio of metformin in lactating mothers and to estimate infant exposure.

Methods

Two studies were performed. In study 1, 3 nursing mothers taking metformin were studied throughout a dosing interval at steady state. Blood samples were obtained from 2 suckling infants. In study 2, 5 healthy lactating women who volunteered to express milk after weaning were given metformin, 500 mg, at weaning and were studied for up to 72 hours. In both studies, areas under the plasma and milk concentration‐time curves were estimated, and the milk‐to‐plasma concentration ratio based on area under the concentration‐time curve analysis was derived. The infant dose was calculated by standard methods.

Results

In study 1 the milk‐to‐plasma concentration ratios based on area under the concentration‐time curve analysis were 0.37, 0.50, and 0.71. The estimated “doses” of metformin that would be ingested by the breast‐fed infants were 0.18%, 0.20%, and 0.21% of the maternal doses, adjusted for weight. In the breast‐fed infants, no metformin was detected (n = 2) or adverse effects noted (n = 3). In study 2, the milk‐to‐plasma concentration ratio based on area under the concentration‐time curve analysis was unable to be calculated for 3 subjects because of the unexpected persistence of metformin in milk beyond the study period. For the 2 subjects studied for 72 hours, the milk‐to‐plasma concentration ratios based on area under the concentration‐time curve analysis were 0.27 and 0.47 and the infant doses were 0.11% and 0.25%. The concentration‐time profile for metformin in milk in all subjects was unexpectedly flat.

Conclusions

Metformin appears to be “safe” during lactation because of low infant exposure. The unusual concentration‐time profile for metformin in milk suggests that the transfer of metformin into milk is not solely dependent on passive diffusion.

Clinical Pharmacology & Therapeutics (2003) 73, 71–77; doi: 10.1067/mcp.2003.9
The Effects of Dietary Creatine Supplements on the Contractile Properties of Rat Soleus and Extensor Digitorum Longus Muscles
Authors: McGuire M. , Bradford A. , MacDermott M.
Published: February 2003

Daily creatine supplements (0.258 g kg−1) were administered to adult male Wistar rats (n= 7) in the drinking water. Age matched rats (n= 6) acted as controls. After 5‐6 days, contractile properties were examined in soleus and extensor digitorum longus (EDL) muscle strips in vitro at 30 °C. In soleus muscles, creatine supplements decreased the half‐relaxation time of the isometric twitch from 53.6 ± 4.3 ms in control muscles to 48.4 ± 5.5 ms but had no effect on twitch or tetanic tension or on twitch contraction time. In EDL muscles twitch tension, tetanic tension, twitch contraction and half‐relaxation times were all unaffected by creatine supplements. Creatine supplements increased the fatigue resistance of the soleus muscles but had no effect on that of the EDL muscles. After a 5 min low‐frequency fatigue test, tension (expressed as a percentage of initial tension) was 56 ± 3% in control soleus muscles, whereas that in the creatine‐supplemented muscles was 78 ± 6% (P < 0.01). In the EDL muscles, the corresponding values were 40 ± 2% and 41 ± 9%, respectively. The force potentiation which occurred in the EDL muscles during the initial 20‐30 s of the fatigue test was 170 ± 10% of initial tension in the control muscles 24 s after the initial stimulus train but was reduced (P < 0.01) to 130 ± 20% in the creatine‐supplemented muscles. In conclusion, soleus muscle endurance was increased by creatine supplements. EDL endurance was unaffected but force potentiation during repetitive stimulation was decreased.
Receptor‐Coupled Contractility of Uterine Smooth Muscle: From Membrane to Myofilaments
Authors: Lee Y.‐H. , Hwang M.‐K. , Morgan K. G. , Taggart Michael J.
Published: February 2003

A comprehensive understanding of the mechanisms by which agonists control uterine contraction is essential for the successful clinical management of parturition and for the timely treatment of situations involving inappropriate uterine performance. In this review we discuss some of the key stimulatory mechanisms linking receptor occupation at the myometrial plasma membrane with alteration of myofilament activation. We focus on evidence that receptor‐induced membranous recruitment of the small G‐protein rhoA, and its downstream effector rho‐associated kinase (ROK) is crucial to agonist‐induced Ca2+‐sensitisation of uterine contraction and that co‐ordination of this signal transduction pathway may be mediated by the actions of caveolins, proteins integral to specialised membranous regions termed caveolae.
Myosin Light Chain Kinase and the Onset of Labour in Humans
Authors: Moore Frances , Bernal Andrés López
Published: February 2003

Myosin light chain kinase (MLCK) is essential for myometrial contractions induced by calcium‐mobilizing agonists. From the gene of vertebrate smooth muscle/non‐muscle MLCK there are at least four proteins expressed. We have found that both a > 200 and a 137 kDa MLCK are equally expressed in human non‐pregnant (NP) and term pregnant (P) uterine smooth muscle and confirmed that 19 kDa telokin (TK) is only expressed in P myometrium. In addition, we have observed that a MLCK immunogen at ∼ 60 kDa is only expressed in NP myometrium, suggesting that its expression is inhibited during normal pregnancy in a hormonally dependent manner. However, when we compared pregnant myometrium from patients delivered preterm (PT) (< 34 weeks gestation), but not in labour (NIL), with PT patients in labour (IL) we found that PT(IL) samples expressed the ∼ 60 kDa MLCK immunogen and thus displayed a NP phenotype whereas PT(NIL) samples did not express the protein and retained a pregnant phenotype. We hypothesize that the novel ∼ 60 kDa MLCK immunogen contributes to the aberrent contractility associated with preterm labour.
Determinants of Oxygen Uptake Kinetics in Older Humans Following Single‐Limb Endurance Exercise Training
Authors: Bell Christopher , Paterson Donald H. , Kowalchuk John M. , Moy Andrew P. , Thorp David B. , Noble Earl G. , Taylor Albert W. , Cunningham David A.
Published: February 2003

We hypothesised that the observed acceleration in the kinetics of exercise on‐transient oxygen uptake (V̇O2) of five older humans (77 ± 7 years (mean ± S.D.) following 9 weeks of single‐leg endurance exercise training was due to adaptations at the level of the muscle cell. Prior to, and following training, subjects performed constant‐load single‐limb knee extension exercise. Following training V̇O2 kinetics (phase 2, τ) were accelerated in the trained leg (week 0, 92 ± 44 s; week 9, 48 ± 22 s) and unchanged in the untrained leg (week 0, 104 ± 43 s; week 9, 126 ± 35 s). The kinetics of mean blood velocity in the femoral artery were faster than the kinetics of V̇O2, but were unchanged in both the trained (week 0, 19 ± 10 s; week 9, 26 ± 11 s) and untrained leg (week 0, 20 ± 18 s; week 9, 18 ± 10 s). Maximal citrate synthase activity, measured from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained leg (week 0, 6.7 ± 2.0 μmol (g wet wt)−1 min−1; week 9, 11.4 ± 3.6 μmol (g wet wt)−1 min−1) but was unchanged in the untrained leg (week 0, 5.9 ± 0.5 μmol (g wet wt)−1 min−1; week 9, 7.9 ± 1.9 μmol (g wet wt)−1 min−1). These data suggest that the acceleration of V̇O2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was not a result of increased O2 delivery.
Metabolic Changes in Single Human Muscle Fibres During Brief Maximal Exercise
Authors: Karatzaferi C. , de Haan A. , van Mechelen W. , Sargeant A. J.
Published: February 2003

Changes in high‐energy phosphate levels in single human skeletal muscle fibres after 10 s of maximal (all‐out) dynamic exercise were investigated. Muscle biopsies from vastus lateralis of two volunteers were collected at rest and immediately post exercise. Single muscle fibres were dissected from dry muscle and were assigned into one of four groups according to their myosin heavy chain (MyHC) isoform content: that is type I, IIA, IIAx and IIXa (the latter two groups containing either less or more than 50% IIX MyHC). Fragments of characterised fibres were analysed by HPLC for ATP, inosine‐monophosphate (IMP), phosphocreatine (PCr) and creatine levels. After 10 s of exercise, PCr content ([PCr]) declined by approximately 46, 53, 62 and 59% in type I, IIA, IIAx and IIXa fibres, respectively (P < 0.01 from rest). [ATP] declined only in type II fibres, especially in IIAx and IIXa fibres in which [IMP] reached mean values of 16 ± 1 and 18 ± 4 mmol (kg dry mass)−1, respectively. While [PCr] was reduced in all fibre types during the brief maximal dynamic exercise, it was apparent that type II fibres expressing the IIX myosin heavy chain isoform were under a greatest metabolic stress as indicated by the reductions in [ATP].