Existence and uniqueness of solutions in general multisolute renal flow problems

This paper considers systems of differential equations that describe flows in renal networks. The flow geometry is of the type that occurs in modelling the renal medulla. The unknowns in the system include the flow rate, the hydrostatic pressure, and the concentrations of the various solutes. Existence and uniqueness of solutions of the appropriate boundary value problems are established, in the case of small permeability coefficients and transport rates, or large diffusion coefficients and small resistance to flow constants.Work supported in part by NIH Grants 5-R01-AM28617 and 7-R01-DK38817Work supported in part by NIH Grant 5-R01-AM20373     

Dictyosome-like structures from guinea-pig testes lack galactosyltransferase,a Golgi apparatus marker

Summary More than twenty different enzyme activities of fractions containing dictyosome-like structures (DLS) as a dominant cell component were monitored. Plasma membrane vesicles were a major contaminant of the DLS fractions, which, presumably as a consequence, were enriched somewhat in plasma membrane markers. The lysosomal enzymes arylsulfatase and latent acid phosphatase were present in the DLS fractions as were the Golgi apparatus activities thiamine pyrophosphatase and nucleoside diphosphatase. The presence of the latter two enzymes in DLS, plus NADH-ferricyanide reductase, has been verified from cytochemistry. On the other hand, the Golgi apparatus marker, galactosyltransferase, was not enriched in DLS fractions and appeared to be absent. This latter finding, verified from cytochemistry with isolated DLS fractions and, in situ, from [³H]galactose incorporation by testis tubules with analysis by autoradiography, provides the first clear biochemical characteristic that serves unequivocally to distinguish DLS from conventional Golgi apparatus.Work supported in part by a grant from the National Institutes of Health HD 11508     

On a conjecture concerning population growth in random environment

Discrete stochastic models are constructed and their limit diffusion processes are derived to shed light on a controversial conjecture regarding the effects of environmental variance on the asymptotic behavior of a population subject to logistic growth in random environment.Work supported in part by the National Group for Mathematical Information Sciences (GNIM) of the National Council for Research     

The early growth of cancer

In this paper, we compare two types of stochastic models for the initial growth of cancerous tumors. In one type, the random element enters via the initial time of growth or via the initial size of the growth clone. In the other type, tumors differ from one another essentially via their growth rates. We present a simple test to distinguish between the two types when tumor size distributions are available from several time points. Size distributions are the key elements of such kinetic analysis given the limitation that an individual tumor can be measured only once, at the time of sacrifice of an experimental animal. We discuss these concepts in connection with data from particular experiments on carcinogenic growth in the livers of mice.Presented in part at the 1983 ORSA-TIMS Applied Probability meeting in Lexington, Kentucky. Work supported in part by NIH Grants CA 15664 and CA 25522.Recipient of a fellowship award from NIH Training Grant 5-T32-Es 07015-07.     

A new explanation of the glitch phenomenon

Summary We consider a discrete model for asynchronous circuits and show that, under very mild restrictions, this model excludes the existence of glitch-free arbiters. This result contradicts a long standing conjecture that the nonexistence of glitch-free arbiters is due to the continuous nature of such circuits.Work supported in part by Office of Naval Research Contract N00014-89-J-1913     

Inference algorithms for developmental systems with cell lineages

An algorithmic formulation is presented for the inference procedure concerning lineage models. The problem is to find lineage rules from observed sequences of tree structures under the assumption that no interactions take place in the course of development and that sufficiently frequent observations are available at equal time intervals. The underlying structural pattern is taken to be a OL system, and the goal is to find propagating and deterministic OL schemes with minimal properties satifsying certain biological reliance criteria. Upper bounds have been found for the complexity of the inference algorithms. This work was supported in part by Grant A0243 of the Natural Sciences and Engineering Research Council of Canada.     

Quantification of creative kinase isoenzymes by a radioimmunoassay

Summary It is not known whether loss of enzyme activity from the circulation is due to denaturation, inactivation or removal of intact enzyme molecules. This is in part due to the lack of an assay to measure enzyme protein concentration since available assays measure only enzyme activity. Radioimmunoassays for plasma enzymes and isoenzymes have not been possible because of oxidation in radioactive labelling by conventional methods and the problem of subunit dissociation. In the present study, antibodies specific to the B and M subunits of creatine kinase isoenzymes were obtained by immunization of rabbits with canine BB and MM creatine kinase. Anitgens (MM and BB) were radioactively labelled with ¹²⁵I by acylation, avoiding the problem of oxidation and subunit stabilized by mercaptoethanol (0.020 m) and Trisbuffer (1.6 m). A radioimmunoassay capable of detecting picogram amounts of CK isoenzymes was developed which measures the concentration of enzyme protein rather than activity. The method was shown to provide a sensitive quantitative method for analysis of plasma CK isoenzymes in dogs after myocardial infarction produced by coronary occlusion. This technique may provide a prototype for the development of radioimmunoassays for other plasma isoenzymes and should help to elucidate the nature of the disappearance of isoenzymes from the circulation.Work from the authors' laboratory was supported in part by the National Institutes of Health Grant HL 17646, SCOR in Ischemic Heart Disease     

The Ornstein-Uhlenbeck process as a model for neuronal activity

Mean and variance of the first passage time through a constant boundary for the Ornstein-Uhlenbeck process are determined by a straight-forward differentiation of the Laplace transform of the first passage time probability density function. The results of some numerical computations are discussed to shed some light on the input-output behavior of a formal neuron whose dynamics is modeled by a diffusion process of Ornstein-Uhlenbeck type.Work supported in part by the Group for Mathematical Information Science (GNIM) of the National Council for Research     

Aqueous extraction of gibberellins from pea

Summary Aqueous buffers were used to extract gibberellin-like substances from pea tissue. The method possesses several distinct advantages when compared with extraction methods using organic solvents. Aqueous buffer extracts can be prepared more rapidly and produce extracts which are free of pigments and other alcohol soluble materials.Extraction of pea with aqueous buffer has indicated the presence of two gibbrellin-like substances in addition to those previously described.Work was supported by National Science Foundation Grant No. GB-5863     

Endothelial cell lineages of the heart

During early gastrulation, vertebrate embryos begin to produce endothelial cells (ECs) from the mesoderm. ECs first form primitive vascular plexus de novo and later differentiate into arterial, venous, capillary, and lymphatic ECs. In the heart, the five distinct EC types (endocardial, coronary arterial, venous, capillary, and lymphatic) have distinct phenotypes. For example, coronary ECs establish a typical vessel network throughout the myocardium, whereas endocardial ECs form a large epithelial sheet with no angiogenic sprouting into the myocardium. Neither coronary arteries, veins, and capillaries, nor lymphatic vessels fuse with the endocardium or open to the heart chamber. The developmental stage during which the specific phenotype of each cardiac EC type is determined remains unclear. The mechanisms involved in EC commitment and diversity can however be more precisely defined by tracking the migratory patterns and lineage decisions of the precursors of cardiac ECs. Work carried out by the authors is supported in part by the NIH.     

Studies on the arrangement of nucleoprotein in elongate sperm heads

Sperm from Nucella lapillus and Gallus domesticus were treated with the enzymes pronase and trypsin and 8M urea to break down the nuclei. Preparations were dried by the critical point method and rotary shadowed with platinum/ carbon prior to examination with the electron microscope. The patterns of breakdown in the nuclei seen after experimental treatment show a close correlation with the patterns of nuclear condensation which occurs during spermiogenesis. No evidence was found to indicate boundaries between chromosomes. The arrangement of chromosomes within sperm nuclei and condensation patterns in spermiogenesis are discussed.Work supported in part by NSF University Science Development Award GU-1154.     

Numerical simulation of a stochastic model for cancerous cells submitted to chemotherapy

A stochastic model is proposed to study the problem of inherent resistance by cell populations when chemotherapeutic agents are used to control tumor growth. Stochastic differential equations are introduced and numerically integrated to simulate expected response to the chemotherapeutic strategies as a function of different parameters. Satisfactory demonstration runs of the model indicate that it could represent a useful tool in verifying the results of experimental and clinical chemotherapy courses and planning treatment strategies. Some types of behaviour are illustrated graphically.Work supported by the C.N.R. Grants: 85.02652.01; 86.02116.01     

Calcium and inositol trisphosphate receptors

Work from the authors' laboratory is supported by the Wellcome Trust, and the Medical, and Agricultural and Food Research Councils. CWT is a Lister Institute Research Fellow.     

Investigation of Antimicrobial,Anti-Quorum Sensing,and Cytotoxic Activities of Flavonoids Isolated from Pulicaria armena Boiss. & Kotschy ex Boiss. (Asteraceae)

This is the first report on the separation and biological assessment of all metabolites derived from Pulicaria armena (Asteraceae) which is an endemic species narrowly distributed in the eastern part of Turkey. The phytochemical analysis of P. armena resulted in the identification of one simple phenolic glucoside together with eight flavon and flavonol derivatives whose chemical structures were elucidated by NMR experiments and by the comparison of the spectral data with the relevant literature. The screening of all molecules for their antimicrobial, anti-quorum sensing, and cytotoxic activities revealed the biological potential of some of the isolated compounds. Additionally, quorum sensing inhibitory activity of quercetagetin 5,7,3’ trimethyl ether was supported by molecular docking studies in the active site of LasR which is the primary regulator of this cell-to-cell communication system in bacteria. Lastly, the critical molecular properties indicating drug-likeness of the compounds isolated from P. armena were predicted. As microbial infections can be a serious problem for cancer patients with compromised immune systems, this comprehensive phytochemical research on P. armena with its anti-quorum sensing and cytotoxic compounds can provide a new approach to the treatment.     

Distribution of enteroglucagon- and polypeptide YY-immunoreactive cells in the gastrointestinal tract of the white-belly opossum (Didelphis albiventris)

Summary Several segments of the gastrointestinal tract of the white-belly opossum Didelphis albiventris were investigated immunocytochemically for the occurrence of polypeptide YY (PYY) and enteroglucagon (GLU). PYY- and GLU-immunoreactive cells were observed in the lower part of the ileum, cecum and colon. These cells were seen to emit cytoplasmic basal processes to the neighbouring cells with a number of them reaching the glandular lumen via apical cytoplasmic process. GLU-immunoreactive cells were also present in the oxyntic mucosae and in the pancreatic duct. Staining of consecutive sections for the two polypeptides, respectively, reaveled the coexistence of immunoreactivity for PYY and GLU in the same cell type.Work supported by grants from FINEP and CNPq (Brazil)     

Polycentric chromosomes induced by X-rays in giant cells of Chinese hamster in vitro

The induction of polycentric chromosomes by X-rays supports a previous interpretation that at least some giant cells are polyploid cells that result from the repetition of endomitosis.Work supported by U.S. Atomic Energy Commission.     

Spatial competition among porifera: Solution by epizoism

Summary Sponges settling on solid substrates which are separated by sediment bottoms compete for the limited space. Some species have solved this problem by occurring as epizoans, thus avoiding the risk of being expelled from the habitat. The supporting species on the other hand, are specialized in that they possess skeletogenous ectosomal structures and aquiferous processes to maintain their integrity and to escape starvation or suffocation. Although specimens are sometimes intimately interwoven no chimaerid mixing of tissues was observed.This work was supported in part by Smithsonian Research Foundation Grant Sg 068104. I thank Dr. H. Forstner (Innsbruck) for his assistance in the field. Miss M. Dwyer prepared the drawings.     

The fine structure of barley aleurone cells

Summary The ultrastructural morphology of both dry and water-imbibed barley aleurone cells is described. The aleurone cell is characterized by the presence of numerous aleurone grains and spherosomes. In addition, it contains organelles typical of other plant cells including structures similar to microbodies, and rough endoplasmic reticulum characterized by the presence of numerous polyribosomes. It is inferred that the morphological specialization of aleurone cells is related to their biochemical specialization.Work supported by National Science Foundation grant GB5863. The skillful technical assistance of Mrs. Janet Price is gratefully acknowledged.     

Sequence Representation and Prediction of Protein Secondary Structure for Structural Motifs in Twilight Zone Proteins

Characterizing and classifying regularities in protein structure is an important element in uncovering the mechanisms that regulate protein structure, function and evolution. Recent research concentrates on analysis of structural motifs that can be used to describe larger, fold-sized structures based on homologous primary sequences. At the same time, accuracy of secondary protein structure prediction based on multiple sequence alignment drops significantly when low homology (twilight zone) sequences are considered. To this end, this paper addresses a problem of providing an alternative sequences representation that would improve ability to distinguish secondary structures for the twilight zone sequences without using alignment. We consider a novel classification problem, in which, structural motifs, referred to as structural fragments (SFs) are defined as uniform strand, helix and coil fragments. Classification of SFs allows to design novel sequence representations, and to investigate which other factors and prediction algorithms may result in the improved discrimination. Comprehensive experimental results show that statistically significant improvement in classification accuracy can be achieved by: (1) improving sequence representations, and (2) removing possible noise on the terminal residues in the SFs. Combining these two approaches reduces the error rate on average by 15% when compared to classification using standard representation and noisy information on the terminal residues, bringing the classification accuracy to over 70%. Finally, we show that certain prediction algorithms, such as neural networks and boosted decision trees, are superior to other algorithms.This research was supported in part by the Natural Sciences and Engineering Research Council of Canada (NSERC).     

Improved technique for the reversion of Histoplasma capsulatum in tissue culture

Summary Reversion ofHistoplasma capsulatum mycelia to the parasitic yeast phase was accomplished in stationary cultured HeLa cells. Fresh guinea pig serum in either Hely or Medium 199 gave excellent conversion. Horse, human, calf, and chicken serum permitted conversion, but to a lesser extent as measured by subsequent growth on blood agar. No apparent differences were found with respect to conversion between 2, 4, and 8-week old mycelial inoculum.Work reported in this paper was supported in part by Grant 2 T1 AI 123 of the National Institutes of Health, U.S. Public Health Service.