Synthesis of novel deoxynucleoside S-methylphosphonic acids using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new equivalent of mercaptomethylphosphonate

The synthesis of the novel nucleotide analogues 5'-deoxynucleoside-5'-S-methylphosphonates, starting from 5'-deoxy-5'-haloribonucleosides, 5'-O-tosylribonucleosides, and 2'-O-triflylnucleosides, is described. The phosphonothiolation of these compounds was achieved using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new, odourless, and efficient equivalent of mercaptomethylphosphonate. The thiolate anion of mercaptomethylphosphonate was generated in situ from the isothiouronium salt in both protic and aprotic solvents using two equivalents of sodium iso-propoxide. The prepared nucleoside 5'-S-methylphosphonates were deprotected, and the free phosphonic acids were transformed into diphosphoryl derivatives (the NTP analogues). Both mononucleotides and NTP analogues were studied as substrates/inhibitors of several enzymes that are involved in the nucleoside/nucleotide metabolism.     

Determination of pK(a) values of N-heterocyclic bases by fluorescence spectrophotometry

Fluorimetry is a relatively fast and accurate means of determining the dissociation constants of sparingly soluble heterocyclic bases. Complications can arise, however, from the dependence of fluorescence on excited-state as well as ground-state acid-base chemistry. Several approaches to circumventing or compensating for this difficulty are discussed. To demonstrate the utility of the methods, the pK(a), values of the conjugate acids of two bases are evaluated by the methods described.     

A simple method for the determination of uranium and thorium by delayed neutron counting

A simple method for the determination of uranium and thorium by delayed neutron counting is described. One portion of the sample is irradiated in a reactor and the delayed neutrons are counted. Another portion of the sample is mixed with B₄ C powder absorbing the thermal neutrons, and irradiated in the same position. From those data, both uranium and thorium can be calculated when a quantitative calibration has been made beforehand. The detection limits for the pure elements are 0.07 ppm for uranium and 2 ppm for thorium with the minimum analyzing time being 2 min. The accuracy of the method is investigated by comparing results obtained by the method described here with results obtained by epithermal activation analysis.     

THE weighted histogram analysis method for free-energy calculations on biomolecules. I. The method

The Weighted Histogram Analysis Method (WHAM), an extension of Ferrenberg and Swendsen's Multiple Histogram Technique, has been applied for the first time on complex biomolecular Hamiltonians. The method is presented here as an extension of the Umbrella Sampling method for free-energy and Potential of Mean Force calculations. This algorithm possesses the following advantages over methods that are currently employed: (1) It provides a built-in estimate of sampling errors thereby yielding objective estimates of the optimal location and length of additional simulations needed to achieve a desired level of precision; (2) it yields the “best” value of free energies by taking into account all the simulations so as to minimize the statistical errors; (3) in addition to optimizing the links between simulations, it also allows multiple overlaps of probability distributions for obtaining better estimates of the free-energy differences. By recasting the Ferrenberg–Swendsen Multiple Histogram equations in a form suitable for molecular mechanics type Hamiltonians, we have demonstrated the feasibility and robustness of this method by applying it to a test problem of the generation of the Potential of Mean Force profile of the pseudorotation phase angle of the sugar ring in deoxyadenosine. © 1992 by John Wiley & Sons, Inc.     

Multiplexing and double band filtering with common-multimodecavities

A novel multiplexing and double band filtering (DBF) method is established. DBF refers to two-port equipment which serves two transmit frequency channels simultaneously. The methods build on frequency-independent resonance modes, excited within a common multimode cavity (CMC), which are assigned to different channel filters. The design principles are presented for cylindrical CMCs by way of example. It is shown that combining CMCs with advanced coupling methods produces a multitude of new design variants. Initial experimental results are presented for a diplexer and DBF equipment that are both realized with only two double-dual TE₁₁₂/TM₁₁₀ CMCs and a novel iris-providing four intercavity couplings-to perform two four-pole elliptic function filter responses     

Inline TM/sub 110/-mode filters with high-design flexibility by utilizing bypass couplings of nonresonating TE/sub 10/01/ modes

This paper presents a new class of pseudoelliptic function filters that are based on compact inline TM/sub 110/-mode cavity configurations. No structural folding is required. The bypass couplings are implemented through the nonresonating TE/sub 10/01/ modes so that arbitrarily positioned transmission zeros can be implemented. Design guidelines to generate a given transmission zero on the desired side of the passband and how to control it are presented. To demonstrate its flexibility, the approach is illustrated at examples of four-pole inline filters providing Chebyshev, elliptic-function-type, and asymmetric characteristics. Performance comparisons with different numerical codes validate the designs. A fourth-order pseudoelliptic filter with four transmission zeros is then designed, constructed, and measured. Excellent agreement between simulated and experimental results verifies the approach.     

A universal building block for advanced modular design of microwave filters

A universal building block for modular design of microwave filters is introduced. The second order block contains two resonators which are not coupled to each other. By adjusting the strengths and signs of its coupling coefficients, the block can be used to design bandpass, bandstop and linear-phase filters. For bandpass filters, Chebychev as well as symmetric and asymmetric pseudo-elliptic responses with one or two finite transmission zeros can be designed. For linear-phase filters, two finite transmission zeros can placed practically anywhere in the complex plane as long as the realizability condition is met. Bandstop filters with no finite reflection zeros as well as symmetric and asymmetric pseudo-elliptic responses with one or two finite reflection zeros can be achieved by the same building block. The block is so flexible it can even generate bandstop responses with complex finite reflection zeros for group delay control. Higher order filters are designed modularly by cascading the appropriate number of building blocks. Coupling matrices of a number of cases are presented to demonstrate the flexibility and the universality of the building block.