Synthesis and characterization of random and block copolypeptides derived from gamma-methylglutamate and leucine N-carboxyanhydrides.

The synthesis of random and block copolypolyeptides derived from gamma-methylglutamate and leucine N-carboxyanhydrides using Al-Schiff's base complexes and allylamine as initiators is here reported. The copolymer structures were confirmed by (1)H and (13)C NMR. The calculation of the statistical average block lengths reveals the presence of longer methylglutamate units in the copolymer.

Rewiring the exit from mitosis.

The mitotic cell cycle can be described as an alternation between two states. During mitosis, MPF (mitosis promoting factor) is high and keeps inactive its numerous molecular antagonists. In interphase, MPF is inactivated, and the antagonists prevail.

Breath ethanol and acetone as indicators of serum glucose levels: an initial report.

Background: Many volatile organic compounds are present in exhaled breath and may represent by-products of endogenous biological processes. Ethanol is produced via alcoholic fermentation of glucose by gut bacteria and yeast, while acetone derives from oxidations of free fatty acids, influenced by glucose metabolism. We hypothesized that the integrated analysis of breath ethanol and acetone would provide a good approximation of the blood glucose profile during a glucose load.

Steady states and oscillations in the p53/Mdm2 network.

p53 is activated in response to events compromising the genetic integrity of a cell. Recent data show that p53 activity does not increase steadily with genetic damage but rather fluctuates in an oscillatory fashion. Theoretical studies suggest that oscillations can arise from a combination of positive and negative feedbacks or from a long negative feedback loop alone.

Chiroptical switching polyguanidine synthesized by helix-sense-selective polymerization using [(R)-3,3'-dibromo-2,2'-binaphthoxy](di-tert-butoxy)titanium(IV) catalyst.

A series of chiral binaphthyl titanium alkoxide complexes were synthesized. Among them, chiral titanium complex [(R)-3,3'-dibromo-2,2'-binaphthoxy](di-tert-butoxy)titanium(IV) (R-3) exists as a crystallographic C2 dimer in the solid state but a monomer in solution at room temperature. Application of R-3 in the helix-sense-selective polymerization of achiral carbodiimide, N-(1-anthryl)-N'-octadecylcarbodiimide (1), yielded a well-defined regioregular, stereoregular poly[N-(1-anthryl)-N'-octadecylguanidine] (poly-1b) with a relatively narrow polymer dispersity index of 2.

[New possibilities in insulin therapy].

In the last few years huge progress in the development of new drugs for diabetes is present. In insulin therapy there have also been novelties with the arrival of new insulins (insulin analogues) specially designed to have better pharmacokinetic and pharmacodynamic properties. New possibilities for insulin delivery are in development, which could spare the patients from painful injections.

The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity.

gamma-Secretase is an intramembrane cleaving protease involved in Alzheimer's disease. gamma-Secretase occurs as a high molecular weight complex composed of presenilin (PS1/2), nicastrin (NCT), anterior pharynx-defective phenotype 1 and PS enhancer 2. Little is known about the cellular mechanisms of gamma-secretase assembly.

Size control in growing yeast and mammalian cells.

Background: In a recent publication it was claimed that cultured mammalian cells, in contrast to yeasts, maintain a constant size distribution in the population without a size checkpoint. This inference may be challengeable.

Results: (1) It is argued that "weak" size control implies the existence of a checkpoint, and unfortunately the technique used by Conlon and Raff might obscure such a weak mechanism.

A model for restriction point control of the mammalian cell cycle.

Inhibition of protein synthesis by cycloheximide blocks subsequent division of a mammalian cell, but only if the cell is exposed to the drug before the "restriction point" (i.e. within the first several hours after birth).

Integrative analysis of cell cycle control in budding yeast.

The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling the complexities of molecular regulatory networks. The budding yeast cell cycle is a challenging test case for this approach, because the control system is known in exquisite detail and its function is constrained by the phenotypic properties of >100 genetically engineered strains.

Modelling the fission yeast cell cycle.

The molecular networks regulating basic physiological processes in a cell can be converted into mathematical equations (eg differential equations) and solved by a computer. The division cycle of eukaryotic cells is an important example of such a control system, and fission yeast is an excellent test organism for the computational modelling approach. The mathematical model is tested by simulating wild-type cells and many known cell cycle mutants.

Helix-sense selective polymerization of carbodiimides: building permanently optically active polymers from achiral monomers.

The helix-sense selective polymerization of achiral monomers by homochiral catalysts was investigated. Polymerization of chiral carbodiimides (N-(R)-2,6-(dimethylheptyl)-N'-phenylcarbodiimide) by achiral catalysts yields polymers that undergo mutorotation at elevated temperatures, thus illustrating that these chains are formed under kinetic rather than thermodynamic control. Building on this observation, the polymerization of achiral carbodiimides by (S-BINOL)Ti(OiPr)2, I, was studied.

Stable helical polyguanidines: poly[N-(1-anthryl)-N'-[(R)- and/or (S)-3,7-dimethyloctyl]guanidines].

Using chiral catalysts of (R)- and/or (S)-BINOL-Ti, the asymmetrical polymerization of achiral monomer, N-(1-anthryl)-N'-n-octadecylcarbodiimide, yielded soluble nonregioregular polyguanidines of Poly-R1 and Poly-S1. A racemization process occurred when the toluene solution of Poly-R1 was annealed at elevated temperatures (70-80 degrees C). Kinetic studies reveal this to be a slow process with an activation energy of ca.

Computerized evaluation of mammographic lesions: what diagnostic role does the shape of the individual microcalcifications play compared with the geometry of the cluster?

Objective: The objective of this study was to compare the diagnostic role of features reflecting the geometry of clusters with features reflecting the shape of the individual microcalcification in a mammographic computer-aided diagnosis system.

Materials And Methods: Three hundred twenty-four cases of clustered microcalcifications with biopsy-proven results were digitized at 42-microm resolution and analyzed on a computerized system. The shape factor and number of neighbors were computed for each microcalcification, and the eccentricity of the cluster was computed as well.

Computer-aided classification of BI-RADS category 3 breast lesions.

Purpose: To evaluate a system for computer-aided classification (CAC) of lesions assigned to Breast Imaging Reporting and Data System (BI-RADS) category 3 at conventional mammographic interpretation.

Materials And Methods: A CAC system was used to analyze 106 cases of lesions (42 malignant) that at blinded retrospective interpretation were assigned to BI-RADS category 3 by at least two of four radiologists. The CAC system automatically extracted from the digitized mammograms quantitative features that characterized the lesions.

Mathematical model of the morphogenesis checkpoint in budding yeast.

The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast.

Modelling the controls of the eukaryotic cell cycle.

The eukaryotic cell-division cycle is regulated by three modules that control G(1)/S, G(2)/M and meta/anaphase transitions. By using mathematical modelling, we show the dynamic characteristics of these individual modules and we also assemble them together into a comprehensive model of the eukaryotic cell-division cycle. With this comprehensive model, we also discuss the mechanisms by which different checkpoint pathways stabilize different cell-cycle states and inhibit the transitions that drive cell-cycle progression.

Heart failure management in the elderly postoperative patient.

As the population ages, the elderly will account for a significant portion of surgical cases. These patients have age-related cardiovascular changes and can suffer from multiple chronic disease conditions. Congestive heart failure is a chronic condition that afflicts nearly five million Americans.

Mathematical model of the cell division cycle of fission yeast.

Much is known about the genes and proteins controlling the cell cycle of fission yeast. Can these molecular components be spun together into a consistent mechanism that accounts for the observed behavior of growth and division in fission yeast cells? To answer this question, we propose a mechanism for the control system, convert it into a set of 14 differential and algebraic equations, study these equations by numerical simulation and bifurcation theory, and compare our results to the physiology of wild-type and mutant cells. In wild-type cells, progress through the cell cycle (G1-->S-->G2-->M) is related to cyclic progression around a hysteresis loop, driven by cell growth and chromosome alignment on the metaphase plate.

Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell.

The physiological responses of cells to external and internal stimuli are governed by genes and proteins interacting in complex networks whose dynamical properties are impossible to understand by intuitive reasoning alone. Recent advances by theoretical biologists have demonstrated that molecular regulatory networks can be accurately modeled in mathematical terms. These models shed light on the design principles of biological control systems and make predictions that have been verified experimentally.

Stratification of mammographic computerized analysis by BI-RADS categories.

The Breast Imaging Reporting and Data System (BI-RADS) was implemented to standardize characterization of mammographic findings. The purpose of the present study was to evaluate in which BI-RADS categories the changes recommended by computerized mammographic analysis are most beneficial. Archival cases including, 170 masses (101 malignant, 69 benign) and 63 clusters of microcalcifications (MCs; 36 malignant, 27 benign), were evaluated retrospectively, using the BI-RADS categories, by several radiologists, blinded to the pathology results.

Erythropoietin-induced hypertensive urgency in a patient with chronic renal insufficiency: case report and review of the literature.

Hypertension is a potentially dangerous side effect of erythropoietin treatment; however, extreme elevations in blood pressure are rare. A 75-year-old woman with chronic renal insufficiency was treated with subcutaneous erythropoietin. Three weeks before she started receiving erythropoietin, her hematocrit was 27.

Detriments of tPA for acute stroke in routine clinical practice.

Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication's appropriate use.

The dynamics of cell cycle regulation.

Major events of the cell cycle--DNA synthesis, mitosis and cell division-are regulated by a complex network of protein interactions that control the activities of cyclin-dependent kinases. The network can be modeled by a set of nonlinear differential equations and its behavior predicted by numerical simulation. Computer simulations are necessary for detailed quantitative comparisons between theory and experiment, but they give little insight into the qualitative dynamics of the control system and how molecular interactions determine the fundamental physiological properties of cell replication.