Synthesis of Heterocyclic Ring Systems Using Organometallic Reagents

We developed novel synthetic routes to heterocyclic ring systems by using transition metal-mediated or -catalyzed reactions. A Lewis acid-promoted addition of the propargyl Grignard reagent 2 to the Schiff base 1 followed by a silvermediated oxidative cyclization of the homopropargylamine 3 provided the aryl-substituted pyrrole 4. Combined with a cherroseleetive hydrogenation of the pyrrole ring, this rnethod has been applied to the total synthesis of the biologically active fused indolizidine alkaloids （ ± ）-harmicine and （ ± ）-crispine A. See Fig. 1.     

The Collaborative Cross, a community resource for the genetic analysis of complex traits

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.     

A relative signalling model for the formation of a topographic neural map

The highly ordered wiring of retinal ganglion cell (RGC) neurons in the eye to their synaptic targets in the superior colliculus of the midbrain has long served as the dominant experimental system for the analysis of topographic neural maps. Here we describe a quantitative model for the development of one arm of this map--the wiring of the nasal-temporal axis of the retina to the caudal-rostral axis of the superior colliculus. The model is based on RGC-RGC competition that is governed by comparisons of EphA receptor signalling intensity, which are made using ratios of, rather than absolute differences in, EphA signalling between RGCs. Molecular genetic experiments, exploiting a combinatorial series of EphA receptor knock-in and knockout mice, confirm the salient predictions of the model, and show that it both describes and predicts topographic mapping.     

Partial quantum information

Information--be it classical or quantum--is measured by the amount of communication needed to convey it. In the classical case, if the receiver has some prior information about the messages being conveyed, less communication is needed. Here we explore the concept of prior quantum information: given an unknown quantum state distributed over two systems, we determine how much quantum communication is needed to transfer the full state to one system. This communication measures the partial information one system needs, conditioned on its prior information. We find that it is given by the conditional entropy--a quantity that was known previously, but lacked an operational meaning. In the classical case, partial information must always be positive, but we find that in the quantum world this physical quantity can be negative. If the partial information is positive, its sender needs to communicate this number of quantum bits to the receiver; if it is negative, then sender and receiver instead gain the corresponding potential for future quantum communication. We introduce a protocol that we term 'quantum state merging' which optimally transfers partial information. We show how it enables a systematic understanding of quantum network theory, and discuss several important applications including distributed compression, noiseless coding with side information, multiple access channels and assisted entanglement distillation.     

Hypotensive activity of histidine-containing analogues of C-terminal hexapeptide of Substance P

Summary Four new hexapeptide analogues of C-terminal Substance P fragment with increased solubility in aqueous solutions are described. The peptides contain histidine in positions 6, 8, 9 and 10, respectively. The effect of the structural changes on the hypotensive activity and antigenic properties of analogues was compared. It was found that substitution of amino acid residues in various positions in the C-terminal hexapeptide of Substance P resulted in different effects on the hypotensive and antigenic properties, respectively. Only the [His⁶] SP_6-11 analogue had an unchanged antigenic structure when compared with the C-terminal region of Substance P, but it showed an almost total loss of hypotensive activity. The [His⁹] SP_6-11 analogue retained 50% of the hypotensive activity of the C-terminal hexapeptide but showed a markedly reduced expression of the antigenic epitope localized in this region of Substance P.     

Cholesterol content and cholesterol esterifying activity of various organs in guinea pigs

Summary In various organs of the guinea pig, the total cholesterol content of an organ was significantly correlated with the percentage of esterified cholesterol present in this organ. Cholesterol esterifying capacity was shown in most organs, with highest activities in the adrenals, the spleen and the liver. The significant correlation found between the cholesteryl ester content of an organ and its acyl cholesterol acyltransferase activity suggests a possible role of this enzyme in determining the level of the total and esterified cholesterol in a tissue.This work was supported by a grant Crédit aux Chercheurs du Fonds National de la Recherche Scientifique of Belgium.Acknowledgments. I am indebted to Prof. C. Harvengt for his stimulating interest and helpful suggestions. I wish to thank Y. van Nieuwenhuyze and J. Costermans for their valuable laboratory assistance and Dr H. Baudon for pathological studies.     

Cauchy’s Infinitesimals,His Sum Theorem,and Foundational Paradigms

Cauchy's sum theorem is a prototype of what is today a basic result on the convergence of a series of functions in undergraduate analysis. We seek to interpret Cauchy’s proof, and discuss the related epistemological questions involved in comparing distinct interpretive paradigms. Cauchy’s proof is often interpreted in the modern framework of a Weierstrassian paradigm. We analyze Cauchy’s proof closely and show that it finds closer proxies in a different modern framework.