Hyperbolastic growth models: theory and application

Background  

Mathematical models describing growth kinetics are very important for predicting many biological phenomena such as tumor volume, speed of disease progression, and determination of an optimal radiation and/or chemotherapy schedule. Growth models such as logistic, Gompertz, Richards, and Weibull have been extensively studied and applied to a wide range of medical and biological studies. We introduce a class of three and four parameter models called "hyperbolastic models" for accurately predicting and analyzing self-limited growth behavior that occurs e.g. in tumors. To illustrate the application and utility of these models and to gain a more complete understanding of them, we apply them to two sets of data considered in previously published literature.     

Glioblastoma stem cells

Glioblastomas are highly malignant primary brain tumors with one of the worst survival rates among all human cancers. With a more profound understanding of the cellular and molecular mechanisms of tumor initiation and acquired resistance to conventional radio- and chemotherapy, novel therapeutic targets might be discovered to optimize therapeutic approaches. In this regard, the identification of a small cellular subpopulation, called glioblastoma stem cell or stem-like cells or glioma-initiating cells or brain tumor propagating cells, has gained attention. In this article, we briefly summarize the current state of knowledge about this tumor cell population and discuss future directions for basic and clinical research.     

Ureteral motility in sheep

Ureteral motility was studied in twenty-five sodium pentobarbital-anaesthetized sheep. Mean frequency of the peristaltic waves was 15 per min and the range was 11-19. Frequency was the same throughout the length of the ureter. Mean contraction pressure (cm H2O) was 40 in the upper ureter, 35 in the middle ureter and 31 in the lower ureter. Mean concentration time was 1 sec and range was 0.6-1.5. Mean relaxation time was 1.1 sec and range was 0.7-1.5. Diuresis induced by rapid intravenous administration of physiologic sodium chloride solution abolished the peristaltic activity.     

Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists

A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents. Conformational analysis and superimposition of energy minima conformers of the designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. Electroshock and pentylenetetrazole-induced lethal convulsion tests showed that the introduction of an amino group in position 2 of 1,3,4-oxadiazole ring and a fluoro substituent at para position of benzylthio moiety had the best anticonvulsant activity. It seems this effect is mediated through benzodiazepine receptors mechanism.     

Hydrolysis of organic phosphates by corn and soybean roots

Because of the importance of organic phosphates as sources of P for plants, this work was performed to study the hydrolysis of nine organic phosphates by sterile, intact corn (Zea mays L.) and soybean (Glycine max L.) roots. Results showed that the rates of hydrolysis ofp-nitrophenyl phosphate (PNP) in buffered solutions by roots of three varieties of corn and three varieties of soybean ranged from 13 to 22 μmol PO₄−P g⁻¹ root h⁻¹ and from 2.1 to 2.2 μmol PO₄−P 0.1 g⁻¹ root h⁻¹, respectively. The average rate of hydrolysis of PNP in nonbuffered solutions was 2- to 3-fold lower for corn roots and 6- to 10-fold lower for soybean roots as compared with those obtained with buffered solutions. The orthophosphate released from hydrolysis of organic P compounds in buffered solutions during a 48-h incubation of corn roots showed that the maximum rate of hydrolysis of PNP was 4 to 6 times greater than the commonly used substrates: α- and β-glycerophosphates, phenolphthalein diphosphate, and glucose-6-phosphate. The rates of hydrolysis of glucose-6-phosphate and glucose-1-phosphate were similar and about 6- to 12-fold lower than that of PNP. Phosphoethanolamine and phosphocholine were hydrolyzed slightly, ando-carboxyphenyl phosphate was not hydrolyzed. The rates of hydrolysis of organic P compounds in nonbuffered solutions by corn and soybean roots were 1 to 3 and 1 to 10 times lower than those in buffered solutions, respectively. The trends in rates of hydrolysis by soybean roots of buffered organic P substrates were similar to those observed with corn roots, with the exception of glucose-1-phosphate and phosphoethanolamine.     

Importance of sulphur in crop production

Sulphur in agricultural soils occurs in organic and inorganic forms, with organic S accounting for > 95% of the total S. Analysis of a wide range of soils shows that from 25 to 75% of the organic S in soils is HI-reducible, from 7 to 30% is C-bonded, and from 11 to 22% is unidentified S. Nitrogen is associated with S in soil organic matter in a ratio of about 8 : 1, although the extreme ratios may vary from 5: 1 to 13: 1. Laboratory studies showed that humus S is depleted faster than humus N. Mineralization of S in crop residues varied with type of crop residue and soil studied The amounts of S fertilizers (gypsum, elemental S, and sulfuric acid) used in the United States in 1981 and 1982 were 1.9 × 10⁶ and 1.5 × 10⁶ tons, respectively. Of the total amount used in 1982, 3, 5, 20, and 71% were used in the West North Central, Mountain, South Atlantic, and Pacific regions, respecitively. A survey of S deposition at about 100 sites in the United States and many other sites in Canada in 1980 showed that annual addition by precipitation in North America ranged from 0.5 to slightly above 10 kg/ha. The usual ranges of values in concentrations and spatial rates of N, P, and S in precipitation is well within the ranges of these elements in natural waters. Atmospheric sources are important components in meeting crops S requirements and should be considered in benefit-cost analyses relating to S emissions.Contribution from a symposium on the role of sulfur in ecosystem processes held August 10, 1983, at the annual meeting of the A.I.B.S., Grand Forks, ND; Myron Mitchell, convenor.     

A Robust Test for Multi-Sample Location Problems with Unequal Group Variances and Nonnormality

A robust test (to be referred to as M^* test) is proposed for testing equality of several group means without assuming normality and equality of variances. This test statistic is obtained by combining Tiku's MML robust procedure with the James statistic. Monte Carlo simulation studies indicate that the M^* test is more powerful than the Welch test, the James test, and the tests based on Huber's M-estimators over a wide range of nonnormal universes. It is also more powerful than the Brown and Forsythe test under most of nonnormal distributions and has substantially the same power as the Brown and Forsythe test under normal distribution. Comparing with Tan-Tabatabai test, M^* is almost as powerful as Tan-Tabatabai test.     

Probing the interaction of new and biologically active Pd(II) complex with DNA/BSA via joint experimental and computational studies along with thermodynamic,NLO, FMO and NBO analysis

BioMetals - Treatment with transition metal complexes is an efficient method to fight with cancer. Therefore, a new transition metal complex formulated as [Pd(1, 3-pn)(acac)]Cl (pn and acac stand...     

Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine

Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies. The aim of the current study was to investigate the effects of modification of generation 5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface amine grafting. Ethidium bromide exclusion assay results proved the ability of modified carriers to condense DNA. Transfection assay showed higher DNA delivery potential for 30% and 50% grafting with decanoate moieties compared to native G5 PPI and Superfect^TM. 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) and apoptosis experiments showed lower toxicity for modified carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was not significantly different from G5 PPI. Size and zeta potential measurements revealed that polyplex size was less than 200 nm and electrical charges were in the range 14–25 mV. The hydrophobic modifications improved transfection activity and toxicity of G5 PPI without negatively affecting hemocompatibility. These modified carriers are therefore promising candidates for further in vivo investigations.KEY WORDS: gene delivery, hydrophobic modification, nonviral vector, polypropyleneimine, transfection