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The imposition of a minimum total soluble solids (TSS) value as a quality standard for orange-flesh netted melon fruit (Cucumis melo L. reticulatus group) requires either a batch sampling procedure (i.e. the estimation of the mean and standard deviation of a population), or the individual assessment of fruit [e.g. using a non-destructive procedure such as near infrared (NIR) spectroscopy]. Several potential limitations to the NIR assessment of fruit, including the variation in TSS within fruit and the effect of fruit storage conditions on the robustness of calibration models, were considered in this study. Outer mesocarp TSS was 3 TSS units higher at the stylar end of the fruit compared with the stem end, and the TSS of inner mesocarp was higher than outer tissue and more uniform across spatial positions. The linear relationship between the outer 10mm and the subsequent middle 10mm of tissue varied with fruit maturity [e.g. 42 days before harvest (DBH), r2 = 0.8; 13 DBH, r2 = 0.4; 0 DBH, r2 = 0.7], and with cultivars (at fruit maturity, Eastern Star 2001 r2 = 0.88; Malibu 2001 r2 = 0.59). This relationship notably affected NIR calibration performance (e.g. based on inner mesocarp TSS; Rc2 = 0.80, root mean standard error of cross-validation (RMSECV) = 0.65, and Rc2 = 0.41, RMSECV = 0.88 for mature Eastern Star and Malibu fruit, respectively). Cold storage of fruit (0?14 days at 5C) did not affect NIR model performance. Model performance was equivalent when based on either that part of the fruit in contact with the ground or equatorial positions; however, it was improved when based on the stylar end of the fruit.

To study the validity of transdermal assessment of alcohol concentration measured by a lightweight, noninvasive device.

Sugar “imaging” of fruit has previously been reported using NIR filters and relatively expensive (high signal-to-noise) charge-coupled device (CCD) instrumentation. In a bid to use lower cost CCD instrumentation (criterion of less than AU $5,000 total component costs), the signal-to-noise constraint on calibration model performance was investigated by artificially degrading spectra from a 15-bit AtoD system. A low cost 8-bit CCD camera was then used in conjunction with a filter wheel in a transmittance configuration employing three 50 W halogen lamps. Multiple linear regregression calibrations were developed based on absorbance data of five wavelengths (830, 850, 870, 905 and 930 nm) relevant to sugar and water. Calibration models for the sucrose concentration of solutions on a cellulose matrix were poor (R2= 0.4) when based on individual pixel data, but acceptable (R2= 0.98, RMSECV= 1.1) (n= 20, mean = 13.9% total soluble sugars (TSS), SD= 6.04) when based on an average of a 23 × 23 pixel block (i.e. 529 pixels). For a calibration based on melon tissue TSS, using spectral data averaged over groups of 529 pixels, results were poorer than expected (R2= 0.4, RMSEP= 1.74 (n= 163, mean = 9.45, SD= 2.07% TSS). Predicted TSS output for all pixel blocks from an image was used to generate a false colour image. We conclude that this application requires a higher level of signal-to-noise (for example, 10-bit, > 60 dB CCD).

Various source?sink perturbations were employed to alter partitioning to orange flesh melon (Cucumis melo L. reticulatus group) and thus to influence fruit biomass and soluble sugar content (indexed as total soluble solids of fruit juice, % TSS), with attention given to the timing of treatment application. A strong relationship existed between harvest index and fruit mass (r2 = 0.88) in control plants, whereas the correlation with fruit TSS was poor (r2 = 0.11). Augmentation of assimilate supply to fruit early in fruit development (before approx. 21 days before harvest, DBH) resulted in more fruit set and increased fruit biomass, whereas augmentation after 21 DBH resulted in increased fruit TSS. Thus, fruit biomass was increased (1644 cf. 1442 g FW per fruit for control, P = 0.02), but not TSS, on plants in which fruit set was delayed (source biomass increased, harvest index decreased from 59% for control to 38%). Treatment of plants with a cytokinin-based vegetative growth inhibitor at 14 DBH produced fruit with higher TSS (11.3 cf. 10.7% for control). Thinning fruit to leave 1 fruit per plant 1 week before harvest increased the proportion of fruit in a population that exceeded a quality control standard of 10% TSS from 20 to 80%. Variations in plant response with timing of treatment application are interpreted in terms of fruit development (cell division, cell expansion, and sugar accumulation phases). Although a detriment to yield (15 cf. 31 t/ha for control), the fruit thinning treatment was recommended for commercial use and a simple model was developed to calculate the required farm-gate price of fruit to make thinning economically viable.

The response features of amperometric ionophore‐based chemical sensors were evaluated in regular ion‐selective membranes, poly(vinyl chloride) plasticized with o‐nitrophenyl octyl ether, with a H+‐selective chromoionophore as model ionophore. Direct imaging experiments upon discrete applied voltage pulses revealed that the diffusion coefficients in such membranes are very similar to that found in membranes under zero current conditions, at about 10−8cm2s−1. In the potential range that defines the limiting current, it was found by these imaging experiments that the ionophore is saturated at the membrane surface, as expected. The observed concentration profiles could be well described with established diffusion theory. At more extreme potentials, the observed diffusion profiles were different, and could be explained by the extraction of additional, uncomplexed hydrogen ions into the membrane phase. The results were correlated to the amperometric response behavior of the same electrodes. At the limiting current, Cottrell fits were performed, and similar diffusion coefficients were found as in the imaging experiments. The pH‐dependent normal pulse voltammetric responses were analyzed in terms of their half wave potential, and found to show a Nernstian pH response, suggesting that they function in close analogy to their potentiometric counterparts. The breakdown of Nernstian pH response at low pH is explained by extraction of electrolyte into the membrane under these conditions, which renders the interface non‐polarizable and leads to loss of voltammetric features. The results adequately support the previously published response mechanism of such ionophore‐based amperometric sensors, including the origin of the limiting current, the capability of such membranes to be responsive to ion activities, the requirement of applying baseline potentials between pulses, and the reason for the altered selectivity at extreme potentials.

Monitoring biochemical processes relevant to the function, survival, and longevity of tissue-engineered pancreatic constructs is important for the development of an optimum construct design as well as patient care management after implantation. In this report we demonstrate the ability of nuclear magnetic resonance (NMR) techniques to monitor aspects of intracellular metabolism, overall morphology, and distribution of a microencapsulation based bioartificial pancreas in vitroand in vivo.

The biosynthesis of the diterpenoid antineoplastic drug Taxol in Taxus species involves the cyclization of the ubiquitous isoprenoid intermediate geranylgeranyl diphosphate to taxa-4(5),11(12)-diene followed by cytochrome P450-mediated hydroxylation (with allylic rearrangement) of this olefin precursor to taxa-4(20),11(12)-dien-5α-ol, and further oxygenation and acylation reactions. Based on the abundances of naturally occurring taxoids, the subsequent order of oxygenation of the taxane core is considered to occur at C10, then C2 and C9, followed by C13, and finally C7 and C1. Circumstantial evidence suggests that the acetylation of taxadien-5α-ol may constitute the third specific step of Taxol biosynthesis. To determine whether taxadienol or the corresponding acetate ester serves as the direct precursor of subsequent oxygenation reactions, microsomal preparations isolated from induced Taxus cells and optimized for cytochrome P450 catalysis were incubated with each potential substrate. Both taxadienol and taxadienyl acetate were oxygenated to the level of a diol and to higher polyols at comparable rates by cytochrome P450 enzymes of the microsomal preparation. Preparative-scale incubation allowed the isolation of sufficient quantities of the diol derived from taxadienol to permit the NMR-based structural elucidation of this metabolite as taxa-4(20),11(12)-dien-5α,13α-diol, which may represent an alternate route of taxoid metabolism in induced cells. GC-MS-based structural definition of the diol monoacetate derived in microsomes from taxadienyl acetate confirmed this metabolite as taxa-4(20),11(12)-dien-5α-acetoxy-10β-ol, thereby indicating that acetylation at C5 of taxadienol precedes the cytochrome P450-mediated insertion of the C10-β-hydroxyl group of Taxol.

We wished to assess the clinical safety and pharmacokinetics of ascending doses of a synthetic oligodeoxynucleotide (LR-3280) administered after coronary angioplasty. Antisense oligodeoxynucleotides designed to hybridize with target messenger ribonucleic acid (mRNA) in a complementary fashion to inhibit the expression of corresponding protein also have the ability to bind to extracellular growth factors. LR-3280 has been shown to reduce c-myc expression, inhibit growth and collagen biosynthesis in human vascular cells, and reduce neointimal formation in animal models of vascular injury. After successful percutaneous transluminal coronary angioplasty (PTCA), 78 patients were randomized to receive either standard care (n = 26) or standard care and escalating doses of LR-3280 (n = 52) (doses from 1 to 24 mg), administered into target vessel through a guiding catheter. Overall safety was evaluated by clinical adverse events, laboratory tests, and electrocardiograms. Patency was evaluated by quantitative coronary angiography. There were no clinically significant differences between treated and control patients. No adverse effects of LR-3280 on the patency of dilated coronary arteries were observed. Pharmacokinetic data revealed that peak plasma concentrations of LR-3280 occurred at 1 minute over the studied dose range and rapidly decreased after ~ 1 hour, with little LR-3280 detected in the urine between 0-6 hours and 12-24 hours. The intracoronary administration of LR-3280 is well tolerated at doses up to 24 mg and produces no adverse effects in dilated coronary arteries. These results provide the basis for the evaluation of local delivery of this phosphorothioate oligodeoxynucleotide for the prevention of human vasculoproliferative disease.

Childhood-onset schizophrenia (COS) is defined by the development of first psychotic symptoms by age 12. While recruiting patients with COS refractory to conventional treatments for a trial of atypical antipsychotic drugs, we discovered a unique case who has a familial t(1;7)(p22;q21) reciprocal translocation and onset of psychosis at age 9. The patient also has symptoms of autistic disorder, which are usually transient before the first psychotic episode among 40–50% of the childhood schizophrenics but has persisted in him even after the remission of psychosis. Cosegregating with the translocation, among the carriers in the family available for the study, are other significant psychopathologies, including alcohol/drug abuse, severe impulsivity, and paranoid personality and language delay. This case may provide a model for understanding the genetic basis of schizophrenia or autism. Here we report the progress toward characterization of genomic organization across the translocation breakpoint at 7q21. The polymorphic markers, D7S630/D7S492 and D7S2410/D7S646, immediately flanking the breakpoint, may be useful for further confirming the genetic linkage for schizophrenia or autism in this region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:749–753, 2000. Published 2000 Wiley-Liss, Inc.

This investigation implements specifically designed solvent-suppressed adiabatic pulses whose properties make possible the long-term monitoring of 1H NMR detectable metabolites from alginate/poly-l-lysine/alginate (APA)-encapsulated βTC3 cells. Our encapsulated preparations were maintained in a perfusion bioreactor for periods exceeding 30 days. During this prolonged cultivation period, the cells were exposed to repetitive hypoxic episodes of 4 and 24 h. The ratio of the total choline signal (3.20 ppm) to the reference signal (observed at 0.94 ppm assigned to isoleucine, leucine, and valine) decreased by 8–10% for the 4-h and by 20–32% for the 24-h episodes and returned to its prehypoxic level upon reoxygenation. The decrease in the mean value of total choline to reference signal ratio for three 4-h and two 24-h episodes in two different cultures was highly significant (P< 0.01). The rate of recovery by this ratio was slower than the rates of recovery by oxygen consumption, lactate production, or glucose consumption. A step-up in oxygen level led to a new, higher value for the total choline to reference ratio. From spectra of extracts at 400 MHz, it was determined that 63.6% of the total choline signal is due to intracellular phosphorylcholine. Therefore, it is inferred that the observed changes in total choline signal are linked to an oxygen level dependence of the intracellular phosphorylcholine. Several possible mechanisms in which oxygen may influence phosphorylcholine metabolism are suggested. In addition, the implications of these findings to the development of a noninvasive monitoring method for tissue-engineered constructs composed of encapsulated cells are discussed.

Focuses on the best path for priority conservation zone between Algonquin Provincial Park in Ontario and Aditrondack Park in New York. Corridor between the Adirondack Park and the Thousand Islands Region; Function of the corridor; The Fronetac Link; Habitat requirements of all native species; Evaluation of corridors.

Focuses on the mission of the Maine Wildlands Network to establish a system of core areas and linkages that will protect and restore the long-term ecological integrity of Maine. Making and breaking of landscape; Maine's biodiversity; Threats to Maine's natural legacy; Future for Maine's wild species; Limitations to the proposed Maine Wildlands Network.

Ovarian germ cell cancers are rare malignancies accounting for less than 5% of all ovarian cancers. We present a family in which three closely related women were diagnosed with ovarian germ cell malignancies. This family's cancer history prompted a family history investigation of women treated for ovarian germ cell malignancies in the Gynecologic-Oncology Clinic at the University of Wisconsin. One of the eight patients whose family histories were reviewed had an uncle who had been diagnosed with testicular germ cell cancer. A review found six other previously reported families in which more than one relative had been diagnosed with a malignant ovarian germ cell tumor. Additionally, several cases of families with both males and females diagnosed with germ cell cancers have been documented. The low incidence of ovarian germ cell cancers suggests that multiple occurrences in the same family may not be due to chance. Rather, it is possible that a gene conferring susceptibility to ovarian germ cell cancers, and possibly to germ cell tumors in males as well, is present in at least some of these families. Am. J. Med. Genet. 84:43–46, 1999. © 1999 Wiley-Liss, Inc.

Mortality and survival of white-tailed deer Odocoileus virginianusfawns (N = 29) were studied from birth to one year of age during 1991–95 on Mount Desert Island (MDI), Maine, where deer hunting is prohibited, coyotes Canis latranshave become recently established, and protected U.S. National Park lands are interspersed with private property. The rate of predator-caused mortality was 0.52, with coyote predation (N = 8) accounting for at least 47% of mortalities from all causes (N = 17). Mortality rate from drowning was 0.24 (N = 3), and from vehicles 0.14 (N = 3). For fawns radio-collared as neonates, 10 of 14 mortalities occurred during the first two months of life. Annual rate of fawn survival was 0.26. Survival rate from six months to one year was 0.65 and four mortalities (two predation, two drowning) were observed during this interval. A subgroup of fawns (N = 11) captured near a residential area and along the periphery of a coyote territory had a higher rate of survival to one year of age (S = 0.67) than did fawns from all other areas (N = 18, S = 0.00). Recruitment to one year of age was lower than that observed in other deer populations in the northeastern United States. Low recruitment associated with coyote predation and mortality sources associated with humans appears to be limiting white-tailed deer populations in some segments of this insular landscape.

A method has been developed and applied to sodium methylphosphonate for determining the values of JHX from the temperature dependence of the anisotropic motion of the solute. The method reduces the uncertainty of DHX due to solvent effects on JHX. As in methyl fluoride discrepancies are observed between structural parameters calculated from different sets of observed dipolar couplings. Unlike the case of methyl fluoride, correction of the dipolar couplings for vibrations improves consistency of these values. Large correction terms found in the present molecule result from contributions of low frequency vibrations whose excited states are appreciably populated at room temperature. The structural parameters and anisotropic motion determined in a lyotropic mesophase are discussed.

The "mesolayer" theory of turbulence is applied to the problem of rotating boundary layers. The first sections concern smooth surfaces and develop the concept of a mesolayer which, in accordance with earlier work on other fluid systems by the author and collaborators, has a thickness of order (hH)½ where h is the inner length and H is the outer length. In the present problem, h is v/uτ where v is the kinematic viscosity and uτ/f is the friction velocity and H is the Ekman-layer thickness uτ/f. The new results seem to agree with laboratory experiments with rotating fluids.The final section concerns rough surfaces. An experiment in a non-rotating system suggests that a mesolayer in a rotating system should have a thickness of the same form (h0H)½, where the inner length h0 is now the height of the roughness elements.

Investigations are made of turbulence in a stably stratified fluid induced by a source of energy at the bottom. The problem is relevant to mixed layers in the upper oceans and lower atmosphere. When the source of turbulence begins, a growing mixed layer of thickness D appears in the lower portion of the fluid separated from the non-turbulent fluid above by an interfacial layer of thickness h. The lower mixed layer has a very weak buoyancy and the large buoyancy difference across the interface is Δb. The theoretical results depend on a Richardson. number Rˆi = DΔb/u21 or DΔb/w2* where the turbulent velocities in the mixed layer are of order u1 or w* in the cases of mechanical and thermal agitation, respectively.The theory contains a number of results for the case of the oscillating grid: (1) ue/u1 ∼Rˆi-7/4, where ue = dD/dt is the entrainment velocity. This -74 entrainment law compares with a -32 law suggested by several experimenters; (2) Turbulence in the interfacial layer is intermittent with intermittency factor I3 ∼ Rˆi-¾. The turbulent patches have a dimension δ3 ∼DRˆi-¾; (3) The rms vertical velocity in the mixed layer near the interface is w2 ∼u1Rˆi-¼; (4) The buoyancy flux near the interface q2 may be expressed as q2∼w32/D; (5) h ∼ D, as observed in several experiments.In the case of penetrative convection, the entrainment is given by ue/w*=K1Rˆi-1 +K2Rˆi-7/4 where the first term is due to heating alone and the second term arises from the eroding effect of the turbulence and has the same form as in mechanical agitation. The expressions for I3, δ3, w2 and h are the same as above.

Kesterson Reservoir, Merced County, CA, a disposal facility for agricultural drain water, became the object of intense scientific investigation following discovery in 1983 that Se‐laden agricultural drain water was having serious effects on the reproductive success of waterfowl. A remedial measure involving permanent flooding with low‐Se water, aimed at taking advantage of low Se solubility under reducing conditions, was proposed as a means of limiting Se movement into groundwater and biota. A field experiment was undertaken to evaluate the feasibility of the proposed remedial measure, its impact on the quality of shallow groundwater and for quantifying Se immobilization and transport through a newly flooded pond bottom soil. Extensive soil water and groundwater sampling demonstrated that although initial soluble Se concentrations in the top 1.22 m (4 ft) of soil typically ranged from approximately 1000 to 3000 µg L−1, Se concentrations declined dramatically after flooding and elevated concentrations below 1.22 m were observed at only one of five sampling sites. Analysis of the temporal and spatial changes in the distribution of dissolved Se and Cl−indicated that 66 to 108% of the initial soluble Se present in the top 1.22 m was immobilized shortly after flooding. These estimates were consistent with the low Se concentrations observed in shallow monitoring wells. The extent to which Se immobilization occurred correlated inversely with average pore water velocity. Data presented suggest that reducing conditions in the newly flooded soils lead to the microbially mediated transformation of selenate to less soluble or mobile forms.

Ruellia tuberosais a wide‐ranging tropical, perennial herb that has been designated the type species for the large genus Ruellia.To clarify interspecific relationships, the R. tuberosaspecies complex, including R. nudiflora, R. malacosperma, and R. lorentziana, and R. tuberosa, has been proposed as the redefined and restricted genus Ruellia.All other Ruelliaspecies would be transferred to segregate genera. Biosystematic investigations that included artificial hybridization experiments, herbarium comparisons, chromatographic analyses, and cytological studies demonstrated that R. tuberosais genetically related to a number of North American temperate taxa and to certain other tropical species. The narrow definition of Ruelliacannot be supported from the biosystematic evidence at hand. Morphological comparisons suggest that R. tuberosamay be a primitive component in a broadened generic concept.

Let $ k$ an odd prime. The set of Steinitz classes of tamely ramified cyclic extensions $ K/k$ is calculated and shown to be a subgroup of the ideal class group of .

Objective: To assess the pharmacodynamics and pharmacokinetics of single oral doses of a new vasodilator-cardiotonic agent, 349U85 hydrochloride [6-piperidino-2(lH)-quinolinone hydrochloride], in healthy male subjects.Methods: This randomized, parallel, double-blind, placebo-controlled, dose escalation trial was conducted at a university-based clinical research center among 27 healthy male subjects. Data measurements used in the study included cardiac index, supine and standing blood pressure, 24-hour ambulatory electrocardiography, and 12-lead electrocardiography.Results: Doses from 2 mg to 250 mg were well tolerated. Cardiac index, supine heart rate, and orthostatic hypotension, indicators of inotropic, chronotropic, and vasodilator effects, respectively, correlated to plasma concentrations of 349U85 and of its metabolite, 661U88. Results suggest that 349U85 may be more responsible for inotropic effects, whereas 661U88 may be more responsible for vasodilatory and chronotropic effects. These results are consistent with the preclinical pharmacologic profile for these two compounds. Headache, orthostatic dizziness, and hypotension tended to occur more frequently at higher doses and were temporally related to drug administration. Pharmacokinetic analyses indicate nonlinearity of 349U85 and 661U88, suggestive of saturation of metabolism and large interindividual variability in maximum plasma drug concentration and area under the plasma concentration—time curve. The source of the variability is not known. The time to maximum distribution was approximately 0.7 hours for both 349U85 and 661U88; the terminal elimination half-life was 1 hour for 349U85 and 3 hours for 661U88. Holter monitoring revealed asymptomatic increases in ventricular and supraventricular ectopic activity in some volunteers; ectopy appeared to be related to the dose of 349U85 and generally occurred at higher doses.Clinical Pharmacology and Therapeutics (1994) 55, 55–63; doi:10.1038/clpt.1994.10

A method is developed to estimate the statistics of the maximum sea states at a given location under hurricane conditions. The method is based on the statistics of hurricane parameters on record in the area near the location of interest. The cumulative probability distributions for hurricane parameters (central pressure deficit, radius of maximum winds, forward velocity, and track location with respect to the selected site) are combined through a Monte Carlo simulation to generate a large number of synthetic hurricanes. Then, using a parameterized wind‐wave model, the maximum sea states are calculated at the selected location for each simulated event. The obtained values are grouped and ranked, and the cumulative probability distribution of sea state is defined. This is then related to the probability of hurricane occurrences to define the probability that the sea state will not exceed a given value within a given time interval or, equivalently, to estimate the average return interval for a given extreme condition.

A simple method is developed for calculating a data base of maximum sea states at a given location in deep water under hurricane conditions. The long‐term statistics of maximum sea states under hurricane conditions can then be estimated from this data base. The method is. based on (1) A parameterized time‐ and space‐dependent wind‐wave model that allows the evaluation of the sea state at a given, fixed location as a function of hurricane parameters (forward velocity, radius of maximum wind, central pressure deficit) and the location of the site relative to the storm track; and (2) the historical record of hurricane parameters for storms that have passed within 100 nautical mi of the selected site. The method differs from the past formulations of equivalent simplicity in two ways: (1) The inclusion of storm‐track distribution as a parameter affecting the sea‐state statistics; and (2) the choice of the wind‐wave model used in hindcasting the historical storms. The method is applied to a site in the Gulf of Mexico.

An experimental study was carried out to investigate the effect of rotation on turbulent mixing in a stratified fluid when the turbulence in the mixed layer is generated by an oscillating grid. Two types of experiments were carried out: one of them is concerned with the deepening of the upper mixed layer in a stable, two-fluid system, and the other deals with the interaction between a stabilizing buoyancy flux and turbulence.In the first type of experiments, it was found that rotation suppresses entrainment at larger Rossby numbers. As the Rossby number becomes smaller (Ro 0.1), the entrainment rate increases with rotation - the onset of this phenomenon, however, was found to coincide with the appearance of coherent vortices within the mixed layer. The radiation of energy from the mixed layer to the lower non-turbulent layer was found to occur and the magnitude of the energy flux was found to be increased with the rotational frequency. It was also observed that vortices are generated, rather abruptly, in the lower layer as the mixed layer deepens.In the second set of experiments a quasi-steady mixed layer was found to develop of which the thickness varies with rotation in a fashion that is consistent with the result of the first experiment. Also the rotation was found to delay the formation of a pycnocline.

Abstract: Erythrityl tetranitrate, a long‐acting organic nitrate, was compared with isosorbide dinitrate in a double‐blind, placebo‐controlled complete crossover study in 15 healthy male volunteers. A digital plethysmogram and ear densitogram were used to assess the physiologic response to these two sublingual nitrates, with the intensity and duration of drug effect calculated by differences in diastolic amplitude intensity before and after drug administration. Both 5 mg sublingual erythrityl tetranitrate and 5 mg isosorbide dinitrate produced significant increases in diastolic amplitude intensity for up to 3 hours. The erythrityl tetranitrate peak effect was less than that of the isosorbide dinitrate, but the incidence of headaches was also less. The ear densitogram was found to be an effective means of assessing the diastolic amplitude intensity changes.

Drug interactions can profoundly alter the absorption of digoxin in tablet form. This study evaluated whether digoxin solution in capsules, a new dosage form with 90% to 100% bioavailability, would reduce such alterations, specifically those caused by cholestyramine and propantheline bromide. The investigation used a six‐treatment, steady‐state, balanced, incomplete block design with 18 healthy adults studied for four continuous two‐week treatment periods. Treatments were either two 0.25 mg digoxin tablets or two 0.20 mg digoxin capsules administered alone, with propantheline, 15 mg qid, or with cholestyramine, 8 g qd. Bioavailability was determined from steady‐state, 24‐hour area under the serum concentration‐time curve (AUC, ng × h/mL) and from 0‐ and 24‐hour trough serum digoxin concentrations (ng/mL). The AUCs for tablets alone, with cholestyramine, and with propantheline were 32.8 ± 13.3 (± SD), 22.4 ± 12.1, and 40.6 ± 13.9, respectively, while corresponding values for capsules were 31.7 ± 9.3, 24.7 ± 7.9, and 35.9 ± 12.8. The trough concentrations for tablets alone, with cholestyramine, and with propantheline were 0.88 ± 0.47, 0.61 ± 0.38, and 1.09 ± 0.35, respectively; trough concentrations for capsules were 0.77 ± 0.28, 0.74 ± 0.28, and 0.96 ± 0.48, respectively. The only significant differences in AUC were seen when comparing tablets alone versus tablets with cholestyramine (P < .0005) and tablets with propantheline (P < .01). A significant finding was also observed when comparing trough concentrations for tablets alone versus tablets with cholestyramine (P < .005). The results confirm (1) bioequivalence of 0.20 mg capsules versus 0.25 mg tablets, (2) significant alterations in tablet bioavailability due to cholestyramine and propantheline, and (3) reduction of these alterations by the capsule dosage form. These findings suggest that digoxin capsules may offer clinical advantages over digoxin tablets in achieving predictable, consistent serum digoxin concentrations in patients receiving cholestyramine, propantheline, and similar drugs.

The bioavailability of oral, sublingual, and chewable tablets of erythrityl tetranitrate (ETN) was evaluated in 15 normal men. In a randomized, complete crossover investigation with nitroglycerin and placebo controls, drug-induced changes in the diastolic amplitude response intensity were measured with a digital plethysmogram. Values for area under the response intensity curve (AUC), maximum response intensity (Imax), and time lapse from dosing to peak response (tmax) were obtained by computer processing and converted to intensity values and AUC segments for specific time intervals. Sublingual nitroglycerin induced a response (p < 0.05) from placebo within the first hour. Although somewhat slower in reaching peak intensity, all forms of ETN induced significant responses over placebo (p < 0.05) for 2 hr, with oral (swallowed) ETN different for 6 hr. Our results indicate that all the ETN dosage forms were bioavailable, with the longest duration of effect by the oral form.Clinical Pharmacology and Therapeutics (1981) 29, 35–39; doi:10.1038/clpt.1981.6

Ten normal subjects were given 0.4 mg digoxin intravenously by bolus injection over 3 to 5 min and by constant-rate infusion for 1 hr. Urinary excretion of digoxin over the next 6 days, as measured by radioimmunoassay, was similar after both the rates of intravenous injection. In one subject, who excreted substantial amounts of digoxin reduction products, no difference was apparent in the amount of reduced metabolites excreted. These results are not in agreement with previous reports of an effect of intravenous infusion rate on urinary digoxin excretion.

Petroleum asphaltenes are defined as material insoluble in pentane or heptane and the nature of the molecular species that constitute asphaltenes has been a well researched subject over the past three decades. These investigations have led to a general consensus of the majority of researchers that asphaltenes contain condensed aromatic systems carrying alkyl, cycloalkyl, and heteroatom substituents. A variety of molecular models has been developed which have been used to explain the behavior of asphaltenes in feedstocks during recovery and processing operationsHowever, an alternate concept introduced the idea that asphaltenes can be defined as a complex mixture of organic compounds of varying molecular weight and polarity. This allows asphaltenes to be described more fully in terms of their behavior during processes and properties in products, such as asphaltThus, the concept can be used to explain, even predict, the incompatibility of asphaltenes with the other petroleum constituents as well as the deposition of asphaltic material on reservoir rock and the occurrence of sediments during refinery operations.

Ruelliais a large, pantropical group of herbs and shrubs that has undergone a long series of changes in classification. Soon after Linnaeus's original description the genus was divided into numerous segregate genera by Nees von Esenbeck and by others. Later Bentham sunk 18 Neesian genera in his expanded concept of Ruellia, and this circumscription has come to be the accepted definition for the plants. Recently Bremekamp revived a number of old segregate groups and described several new ones. He believes Ruellia sensu latois an unwieldy and unnatural assemblage of taxa. Experimental hybridizations have established the existence of species‐complexes (ecospecies) and species‐groups (comparia) in Ruellia. The latter are genetically isolated from other species‐groups, and taxonomically they correspond to certain segregate genera. There is evidence that North American taxa are closely related to tropical species. Since numerous species can be artificially hybridized, application of the ecotype concept may provide a practical means of identifying natural species‐groups. Present evidence suggests that Ruellia, as generally understood, is not a natural, phyletic, unit.

This paper presents adaptive control algorithms which have been designed for use on two applications, namely dissolved oxygen control in activated sludge waste water treatment and control of pH in acidic waste water. Global convergence of the algorithms is established. Simulation studies show that the adaptive control laws can give superior controller performance compared with other conventional control algorithms.

Understanding the biochemical events associated with glucose-stimulated insulin secretion by pancreatic β cells is of importance in gaining insight into both the pathophysiology of diabetes and the development of tissue-engineered bioartificial pancreatic substitutes. We have investigated the effects of glucose concentration on the bioenergetic status and on the metabolic and secretory functions exhibited by mouse insulinoma βTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate (APA) beads. Cells entrapped in APA beads constitute a possible implantable bioartificial pancreas for the long-term treatment of insulin-dependent diabetes mellitus. Our results show that, in entrapped βTC3 cells, the oxygen consumption rate and the intracellular nucleotide triphosphate levels are unaffected by a step change in glucose concentration from 16 mM to 0 mM for 4.5 h and then back to 16 mM. The intracellular Pi level and the ammonia production rate were doubled, while insulin secretion was decreased 10-fold, upon switching from 16 mM to 0 mM glucose. The implications of these findings in the context of pancreatic β cell biochemistry and the mechanism of the ‘Fuel Hypothesis’ are discussed.

The paper discusses an idealized experiment relevant to the flow of air over a heated surface. Two regimes are found and expressions are obtained for buoyancy and momentum fluxes q and τ, mean buoyancy and mean velocity gradients ρz and uz, rms velocity fluctuations, rms buoyancy fluctuations σρ, turbulent length and time scales and eddy viscosity and conductivity.The number determining the two regimes is U = ?u/(ν?ρ)1/3, where ?u is the speed of the heated surface (or the velocity at infinity), — ?ρ is the buoyancy at the surface and ν is the molecular coefficient of viscosity. In the low-speed regime, U is small. In the limit, of course, this corresponds to free convection over a stationary heated plate. The results disagree with two earlier theories by Malkus and Priestley. For example, above the thermal boundary layer, ρz decreases as z-3/2 in the present theory compared with z-2 in the Malkus theory and z-4/3 in the similarity theory of Priestley. The z-3/2 behavior is, however, supported by experiments of Croft. In the present theory σρ decreases as z-1/2 above the thermal boundary layer, and this is in better agreement with the measurements of Townsend than the z-1/3 law of similarity theory. In addition, Townsend's measurements of the “dissipation” function for buoyancy fluctuations δ yield δ proportional to z-3/2 in exact agreement with the present theory.In the high-speed regime U is large and the general result of this paper is similar to the theory of Monin and Obukhov in that molecular coefficients do not directly influence the various mean quantities. However, when z is large, the present theory differs from the similarity theory of Priestley. For example, ρz again decreases as z-3/2 (instead of z-4/3) in agreement with recent atmospheric data of Dyer and of Businger, et al. The basic assumption in the “derivation” of the z-4/3 law is that the momentum flux τ may be considered arbitrarily small at large values of zq/τ3/2, whereas in the present theory there is a lower limit to τ if molecular viscosity and conduction ν and ? are to be neglected entirely.The paper concludes with a discussion of a quantity Ud separating the two regimes. Experimental data suggest Ud ? 44. This corresponds to a ?u of perhaps 60 cm/sec in the atmosphere so that the atmosphere is usually in the high-speed regime. In the oceans, velocities corresponding to Ud = 44 are 5-10 cm/sec.

Presents the short story 'Champion.'

Outlines the different but complementary opportunities banks have to reduce teller and platform-staff costs. Key to success in the teller area; Five-step process for more appropriate matching of the supply and demand for tellers; Four-step process in realizing benefits on the platform; Most attractive aspects of branch staffing improvements.

High resolution proton magnetic resonance spectra of pyrazine, pyrimidine, and pyridazine partially oriented in a lyotropic mesophase have been obtained and analyzed. The distance ratios calculated from the direct dipole-dipole couplings are compared with those reported for microwave and X-ray studies in the gaseous and solid state as well as those determined from NMR investigations of the above solutes in thermotropic nematic phases.The average orientation of the diazines in the oriented lyotropic phase is such that the applied magnetic field is parallel to the molecular plane. In contrast, the average orientation of benzene, furan, thiophene, p-dithiin, and tetrafluoro-1,3-dithietane is such that the molecular ring is on the average perpendicular to the applied magnetic field. Sine benzene, furan, thiophene, and the diazines orient with the molecular plane parallel to the magnetic field in thermotropic nematic phases, contributions from different orienting factors appear to be operative in the lyotropic phase.

THE ASSOCIATION of certain endocrine abnormalities, particularly those of estrogen metabolism, with fairly severe liver disease is common and well known. Some of the clinical signs and symptoms of such association are, in the male, gynecomastia, softening of the testes, loss of axillary hair, impotence, and decreased libido, and, in the female, menstrual disturbances, breast changes and symptoms, and acne. Infertility may occur in both sexes.Some patients with these endocrine abnormalities have clinically evident liver disease; some give a history of having had jaundice in the past but show no other evidence of impaired liver function, and others exhibit no apparent cause in the history or findings for their endocrine or estrogen disturbance. We have become more aware in recent years of the existence of impaired liver function in persons who have been and are otherwise in apparently good health. It is well known that hepatitis with appreciable liver

A description is given of the flow of a three-layer system of immiscible fluids over an obstacle immersed in the lowest liquid. A tentative suggestion is offered that some features of the motion may be similar to the flow of air over the Sierra range near Bishop, California. Some arguments are advanced supporting this suggestion.