Transformation of aminoacyl tRNAs for the in vitro selection of "drug-like" molecules

Evolutionary approaches are regularly used to isolate single molecules with desired activities from large populations of nucleic acids (approximately 10(15)). Several methods have also been developed to generate libraries of mRNA-encoded peptides and proteins for the in vitro selection of functional polypeptides. In principal, such mRNA encoding systems could be used with libraries of nonbiological polymers if the ribosome can be directed to polymerize tRNAs carrying unnatural amino acids. The fundamental problem is that current chemical aminoacylation systems cannot easily produce sufficient amounts of the numerous misacylated tRNAs required to synthesize a complex library of encoded polymers. Here, we show that bulk-aminoacylated tRNA can be transformed into N-monomethylated aminoacyl tRNA and translated. Because poly-N-methyl peptide backbones are refractory to proteases and are membrane permeable, our method provides an uncomplicated means of evolving novel drug candidates.     

An unexpected symmetry of the coulomb potential in the debye-smoluchowski equation

Generalised diffusion processes are discussed using the theory of stochastic processes and several elementary results are proved for the survival probability of a pair of particles with an arbitrary potential. The reaction probability conditioned on reaction ultimately occurring is considered and its backward equation is determined. In the case of the Coulomb potential the probability is shown analytically to be identical in both the attractive and repulsive cases for a given absolute value of r_c. The utility of this result in numerical solutions of the Debye—Smoluchowski equation is discussed.     

GC–MS analysis of phenolic compounds in fuels after conversion to trifluoroacetate esters

The GC–MS characteristics of trifluoroacetate esters of phenolic compounds are discussed. Linear temperature programmed retention indices and total ion current MS response factors of over 120 phenolic esters are reported. The main GC advantages from analysis of trifluoroacetate esters as compared to plain phenols are enhanced volatility and improved resolution. For example, the elution temperature of a given phenol is typically 50 °C greater than that of the corresponding trifluoroacetate ester. Also, while retention of compounds with two trifluoroacetate groups is only moderately greater than mono esters, underivatized dihydroxy compounds are very difficult to elute from any GC column. Complete resolution of isomeric C₀-, C₁- and C₂-alkylphenol esters is readily achieved on conventional fused silica GC columns; resolution of the corresponding underivatized compounds requires specialized GC columns with low temperature limits. In general, mass spectra of trifluoroacetate esters are more characteristic of a given structure than those of the corresponding phenols and may be more rigorously interpreted towards structural elucidation. A table in the report summarizes some of the more important spectral features used in compound identification. Example applications in analysis of coal-, shale- and petroleum-derived materials are presented. Selected ion monitoring is used to determine individual phenolic components in whole distillates; reconstructed ion chromatograms are used to illustrate distributions of selected species as a function of fuel storage and thermal stress.     

The number of components in profile analysis tasks.

The central issue of this paper is how detection of a change in spectral shape depends on the number of components m that define the spectrum. First, a channel theory is reviewed and the predictions relating the detectability of such a change as a function of the number of components are derived. Second, the existing literature is reviewed. Most of it concerns the detection of an increment in a single tone of an m-component, equal-amplitude complex. The data are close (+/- 2 dB) to the predictions of the theory, which suggests that there is a relatively small change in threshold as the number of components increases. The consistency of the data is also discussed and hypotheses for discrepancies are presented. Finally, the results of an experiment measuring the detectability of a special spectral shape change is explored. In this case, all the changes are equal in size but some are opposite in sign, so that the summed change is zero. The results using this "balanced" spectral change are also consistent with the predictions of the theory and show that for this special kind of spectral change thresholds improve by nearly 7 dB as m increases from 4 to 24 components.     

Ultraviolet properties of maximal supergravity

We argue that recent results in string perturbation theory indicate that the four-graviton amplitude of four-dimensional N=8 supergravity might be ultraviolet finite up to eight loops. We similarly argue that the h-loop M-graviton amplitude might be finite for h<7+M/2.     

Spin-exchange-induced circularly polarized molecular fluorescence

We have measured the circular polarization of light emitted from both atomic H and molecular H2 after bombarding H2 with longitudinally polarized electrons. For both atomic and molecular fluorescence near threshold we observe a circular polarization as great as 10% of the electron polarization. This represents the first direct observation of spin transfer in electron-molecule collisions.     

A Direct theory of viscous fluid flow in channels

This paper deals with an Eulerian formulation of the theory of directed fluid sheets appropriate for incompressible, linear viscous fluid flow in channels with arbitrary shapes for their major boundaries which may be moving or fixed. Special cases of the theory are applied to a number of two-dimensional fluid flow problems and these solutions are in general discussed for unsteady flow. Specific applications include fluid flow in a channel whose boundaries are symmetric with respect to a middle plane in the channel, subjected to time-dependent pressure gradient at one end; and to lubrication problems in a general shaped channel when one of the channel walls is a fixed plane while the other is moving with a constant velocity. Flow of a viscous fluid with a free surface over a fixed boundary is also discussed.Dedicated to J. L. Ericksen on the occasion of his Sixtieth Birthday     

The Simulation of Some Simple Control Policies for a Signalized Intersection

The authors present the results of some simulation studies concerned with the computer control of signalized intersections. The simplest model considered is that of two competing random streams. The transient response and delay/flow characteristics of some simple control procedures are investigated. These are based on the Dunne-Potts policy in which the traffic light is switched when the queue of the road with right of way has been dispersed.The model is then developed to consider four competing streams and the control policies are modified accordingly. Similar results to the two-stream case are presented. In the final section turning vehicles are considered by including eight competing streams in the intersection model.     

Where is the shot noise of a quantum point contact?

Reznikov et al. [Phys. Rev. Lett. 75, 3340 (1995)]] have presented definitive observations of nonequilibrium noise in a quantum point contact. Especially puzzling is the "anomalous" peak structure of the excess noise measured at constant current; to date it remains unexplained. We show that their experiment directly reveals the deep link between conservation principles in the electron gas and its low-dimensional, mesoscopic behavior. The keys to that connection are gauge invariance and the compressibility sum rule. These are central not only to the experiment of Reznikov et al., but to the very nature of all mesoscopic transport.