Synthesis of 2,3-dihydro-1,4-dithiinyl nucleosides via Pummerer-type glycosidation

A straightforward procedure for the preparation of nucleoside analogue 1 and its regioisomer 2 containing a dihydro-1,4-dithiin as sugar moiety has been accomplished in four steps by our readily available heterocyclic system 5. Nucleobase insertion was carried out by direct addition of N⁴-acetylcytosine to sulfoxide derivatives via Pummerer-type glycosidation reaction.     

Characterization of a microfluidic dispensing system for localised stimulation of cellular networks

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.     

Strategies for protein folding and design

Fundamental challenges in molecular biology can be addressed by using simple models on a lattice, where statistical mechanics and combinatoric techniques can be employed. The basic premise is that it is sensible to test any proposed method on the simplest of models in order to assess their validity before launching a full-scale attack on realistic problems. In this paper we follow this strategy and we present different efficient schemes to perform protein design and to extract effective amino acid interaction potentials.This work was supported in part by INFM, INFN sez. di Trieste, NASA and NATO.     

X-ray crystal structure of bis(4-nitropyrazol-1-yl)methane,and some empirical rules concerning the bond angles in pyrazoles

The crystal structure of bis(4-nitropyrazol-1-yl)methane has been determined by X-ray diffraction. The nitro groups form angles of 16.45(6) and 11.83(7)°, respectively, with the pyrazole ring to which they are attached. The internal and external angles of the pyrazole rings follow a set of empirical rules: (1) N(1)-N(2)-C(3) is smaller than N(2)-N(1)-C(5); (2) N(2)-C(3)-C(4) is larger than N(1)-N(2)-C(3) and at least one chosen between C(3)-C(4)-C(5) and C(4)-C(5)-N(1); (3) C3-C4-C5 is not the largest internal angle; (4) R1-N1-N2 is smaller than R1-N1-C5; (5) N2-C3-R3 is smaller than R3-C3-C4, or R5-C5-N1 is smaller than C4-C5-R5; (6) C3-C4-R4 and R4-C4-C5 are nearly the same. Provided that the angle considered is not part of another ring, the first five rules are valid for all the pyrazoles investigated up to now, while violation of the last rule is good evidence for steric hindrance or marked asymmetry of the 3- and 5-substituents.     

Cover Picture: Angew. Chem. Int. Ed. 6/2002

The cover picture shows the electric eel, Electrophorus electricus, a source for commercially available acetylcholinesterase. In an experiment described by K. B. Sharpless and M. G. Finn and co‐workers on pp. 1053–1057, a femtomolar inhibitor was assembled by the enzyme from a collection of building blocks containing azide and alkyne functional groups, shown floating in solution. The templated 1,3‐dipolar cycloaddition reaction, producing the inhibitor, is represented by the flare of light at the center of the image.     

Portfolio selection with probabilistic utility

Inspired by statistical physics, we present a probabilistic approach to portfolio selection. Instead of seeking the global extremum of some chosen utility function, we reinterpret the latter as a probability distribution of ‘optimal’ portfolios, and select the portfolio that is given by the mean value with respect to that distribution. Compared to the standard maximization of expected utility, this approach has several attractive features. First, it significantly reduces the excessive sensitivity to external parameters that often plague optimization procedures. Second, it mitigates the commonly observed concentration on too few assets; and third, it provides a natural and consistent way to account for the incompleteness of information and the aversion to uncertainty. Supportive empirical evidence is derived by using artificial data to simulate finite-sample behavior and out-of-sample performance.     

Disposable Electrospun Electrodes Based on Conducting Nanofibers

A new approach for the fabrication of disposable electrochemical surfaces is presented. Conducting fibers have been produced by a two‐step process. Firstly, a fine web mat composed of nylon‐6 and ferric chloride fibers (with diameters of about 200 nm) were electrospun on a flat collector. Afterwards, the electrospun mat was exposed to pyrrole vapor under controlled dry atmosphere until each nylon thread was fully coated with a conducting polypyrrole layer. The conducting fiber mat was finally integrated within an electrochemical cell and used as a disposable sensor device. The suitability of the sensor was tested using phosphate and carbonate organic anions. The large scale fabrication of conducting tissue, in the form of a fine web of spun nanofibers, is relatively fast and inexpensive, and it paves the way to the build up of new disposable electrodes.