After decades of decline, the incidence of tuberculosis in the United States began to increase in 1986, resulting in 52,000 excess cases by 1992 1 . New York City accounted for 14 percent of all cases of tuberculosis in the United States in 1992; the number of cases reported in the city has increased by over 150 percent since 1979 2 . This increase has been especially dramatic among minorities and in specific areas. The increase in tuberculosis has been attributed to coinfection with the human immunodeficiency virus (HIV), 3 , 4 deterioration of the public health infrastructure, 5 social disruption including homelessness and drug . . .
A general linear solvation energy equation has been used to analyze published partition coefficients in the systems water‐octanol (613 solutes), water‐hexadecane (370 solutes), water‐alkane (200 solutes), and water‐cyclohexane (170 solutes). The descriptors used in the equation are R2, an excess molar refraction; π2H, the solute dipolarity/polarizability; πα2H and π2H, the effective solute hydrogen‐bond acidity and basicity; and VX, the characteristic volume of McGowan. It is shown that the water‐octanol partition coefficient is dominated by solute hydrogen‐bond basicity, which favors water, and by solute size, which favors octanol, but solute excess molar refraction and dipolarity/polarizability are also significant. For the water‐alkane partition coefficients, the same factors are at work, together with solute hydrogen‐bond acidity as a major influence that favors water. An analysis of 288 Δlog P values shows that solute hydrogen‐bond acidity is the major factor but that solute hydrogen‐bond basicity and, to a lesser extent, solute dipolarity/polarizability and size are also significant factors that influence the Δlog P parameter.
The IncP alpha promiscuous plasmid (R18, R68, RK2, RP1 and RP4) comprises 60,099 bp of nucleotide sequence, encoding at least 74 genes. About 40 kb of the genome, designated the IncP core and including all essential replication and transfer functions, can be aligned with equivalent sequences in the IncP beta plasmid R751. The compiled IncP alpha sequence revealed several previously unidentified reading frames that are potential genes. IncP alpha plasmids carry genetic information very efficiently: the coding sequences of the genes are closely packed but rarely overlap, and occupy almost 86% of the genome's nucleotide sequence. All of the 74 genes should be expressed, although there is as yet experimental evidence for expression of only 60 of them. Six examples of tandem-in-frame initiation sites specifying two gene products each are known. Two overlapping gene arrangements occupy different reading frames of the same region. Intergenic regions include most of the 25 promoters; transcripts are usually polycistronic. Translation of most of the open reading frames seems to be initiated independently, each from its own ribosomal binding and initiation site, although, a few cases of coupled translation have been reported. The most frequently used initiation codon is AUG but translation for a few open reading frames begins at GUG or UUG. The most common stop-codon is UGA followed by UAA and then UAG. Regulatory circuits are complex and largely dependent on two components of the central control operon. KorA and KorB are transcriptional repressors controlling at least seven operons. KorA and KorB act synergistically in several cases by recognizing and binding to conserved nucleotide sequences. Twelve KorB binding sites were found around the IncP alpha sequence and these are conserved in R751 (IncP beta) with respect to both sequence and location. Replication of IncP alpha plasmids requires oriV and the plasmid-encoded initiator protein TrfA in combination with the host-encoded replication machinery. Conjugative plasmid transfer depends on two separate regions occupying about half of the genome. The primary segregational stability system designated Par/Mrs consists of a putative site-specific recombinase, a possible partitioning apparatus and a post-segregational lethality mechanism, all encoded in two divergent operons. Proteins related to the products of F sop and P1 par partitioning genes are separately encoded in the central control operon.
In many areas of molecular biology there is a need to rapidly extract and analyze genetic information; however, current technologies for DNA sequence analysis are slow and labor intensive. We report here how modern photolithographic techniques can be used to facilitate sequence analysis by generating miniaturized arrays of densely packed oligonucleotide probes. These probe arrays, or DNA chips, can then be applied to parallel DNA hybridization analysis, directly yielding sequence information. In a preliminary experiment, a 1.28 x 1.28 cm array of 256 different octanucleotides was produced in 16 chemical reactioncycles, requiring 4 hr to complete. The hybridization pattern of fluorescently labeled oligonucleotide targets was then detected by epifluorescence microscopy. The fluorescence signals from complementary probes were 5-35 times stronger than those with single or double base-pair hybridization mismatches, demonstrating specificity in the identification of complementary sequences. This method should prove to be a powerful tool for rapid investigations in human genetics and diagnostics, pathogen detection, and DNA molecular recognition.