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Impact constraints on the environment for chemical evolution and the continuity of life.

The Moon and the Earth were bombarded heavily by planetesimals and asteroids that were capable of interfering with chemical evolution and the origin of life. In this paper, we explore the frequency of giant terrestrial impacts able to stop prebiotic chemistry in the probable regions of chemical evolution. The limited time available between impacts disruptive to prebiotic chemistry at the time of the oldest evidence of life suggests the need for a rapid process for chemical evolution of life. The classical hypothesis for the origin of life through the slow accumulation of prebiotic reactants in the primordial soup in the entire ocean may not be consistent with constraints imposed by the impact history of Earth. On the other hand, rapid chemical evolution in cloud systems and lakes or other shallow evaporating water bodies would have been possible because reactants could have been concentrated and polymerized rapidly in this environment. Thus, life probably could have originated near the surface between frequent surface sterilizing impacts. There may not have been continuity of life depending on sunlight because there is evidence that life, existing as early as 3.8 Gyr ago, may have been destroyed by giant impacts. The first such organisms on Earth were probably not the ancestors of present life.

Earth, Planet↗

Continuous in vitro evolution of bacteriophage RNA polymerase promoters.

Rapid in vitro evolution of bacteriophage T7, T3, and SP6 RNA polymerase promoters was achieved by a method that allows continuous enrichment of DNAs that contain functional promoter elements. This method exploits the ability of a special class of nucleic acid molecules to replicate continuously in the presence of both a reverse transcriptase and a DNA-dependent RNA polymerase. Replication involves the synthesis of both RNA and cDNA intermediates. The cDNA strand contains an embedded promoter sequence, which becomes converted to a functional double-stranded promoter element, leading to the production of RNA transcripts. Synthetic cDNAs, including those that contain randomized promoter sequences, can be used to initiate the amplification cycle. However, only those cDNAs that contain functional promoter sequences are able to produce RNA transcripts. Furthermore, each RNA transcript encodes the RNA polymerase promoter sequence that was responsible for initiation of its own transcription. Thus, the population of amplifying molecules quickly becomes enriched for those templates that encode functional promoters. Optimal promoter sequences for phage T7, T3, and SP6 RNA polymerase were identified after a 2-h amplification reaction, initiated in each case with a pool of synthetic cDNAs encoding greater than 10(10) promoter sequence variants.

Bacteriophage T3↗

Continuous in vitro evolution of a ribozyme that catalyzes three successive nucleotidyl addition reactions.

Variants of the class I ligase ribozyme, which catalyzes joining of the 3' end of a template bound oligonucleotide to its own 5' end, have been made to evolve in a continuous manner by a simple serial transfer procedure that can be carried out indefinitely. This process was expanded to allow the evolution of ribozymes that catalyze three successive nucleotidyl addition reactions, two template-directed mononucleotide additions followed by RNA ligation. During the development of this behavior, a population of ribozymes was maintained against an overall dilution of more than 10(406). The resulting ribozymes were capable of catalyzing the three-step reaction pathway, with nucleotide addition occurring in either a 5'-->3' or a 3'-->5' direction. This purely chemical system provides a functional model of a multi-step reaction pathway that is undergoing Darwinian evolution.

Base Sequence↗

Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: studies on two immortal colon cancer cell lines.

Extensive karyotypic analysis was performed on early and late passages of two continuous human cell lines, SW480 and SW620, that were derived from the same colon cancer patient. We cultivated these two cell lines in vitro for a period of 24 months and periodically examined their chromosome constitution. SW480 cells, from passage 138, were injected subcutaneously into 20 nude mice. The tumors that grew in nude mice were then cultivated in vitro for several passages to compare histopathologic findings and tumor growth patterns with clonal chromosomal profiles. Despite some karyotypic diversity, the two cell lines exhibited common marker chromosomes and followed similar patterns of evolution. During subsequent passages, acquisition of new chromosomal abnormalities gave rise to sidelines with a near-diploid genome that frequently underwent endoreduplication. Genomic instability seemed to play an important role in the emergence, growth, and subsequent elimination of the heterogenous sidelines by selection, clonal expansion, and cell death by senescence. Despite continuous growth, both the cell lines occasionally showed telomeric associations and random dicentric and multicentric formations. These lesions were considered evidence of cell senescence and were related to the disappearance of particular sidelines through evolution. Successful evolutionary steps were characterized by elimination of pre-existing marker chromosomes that were subsequently replaced in the karyotype by their cytologically intact homologous chromosomes possibly after selective endoreduplication. Frequent loss of heterozygosity for the chromosomes taking part in this process is postulated. We suggest that one of the mechanisms by which cancer cells bypass senescence may be related to their potential for continuous clonal diversification.

Animals↗

Neutral evolution in spatially continuous populations.

We introduce a general recursion for the probability of identity in state of two individuals sampled from a population subject to mutation, migration, and random drift in a two-dimensional continuum. The recursion allows for the interactions induced by density-dependent regulation of the population, which are inevitable in a continuous population. We give explicit series expansions for large neighbourhood size and for low mutation rates respectively and investigate the accuracy of the classical Malécot formula for these general models. When neighbourhood size is small, this formula does not give the identity even over large scales. However, for large neighbourhood size, it is an accurate approximation which summarises the local population structure in terms of three quantities: the effective dispersal rate, sigma(e); the effective population density, rho(e); and a local scale, kappa, at which local interactions become significant. The results are illustrated by simulations.

Alleles↗

Kock pouch procedures: continuing experience and evolution in 135 cases.

Between April 1985 and January 1989, 135 consecutive patients underwent construction of a Kock pouch (to the skin in 72 patients, a urethral pouch in 45, an ileorectal pouch in 10 and a hemi-Kock pouch augmentation cystoplasty in 8). The operative mortality (30 days) rate was 4.4%. There were 16 early complications (12.4%) leading to 14 reoperations (11%), with a followup of 6 to 60 months. After Kock pouch to the skin, the late complication rate was 26.1% in the Kock-Skinner technique group and 7.4% in the simplified technique group, and 94.2% of the patients were continent. After a urethral Kock pouch daytime continence was achieved in 93% of the patients within 2 months and nighttime dryness was noted in 65% within 3 months. After an ileorectal Kock pouch all patients were continent day and night, as were those after hemi-Kock pouch augmentation, although 5 of the latter patients required intermittent catheterization.

Adolescent↗

100 cases of Mainz pouch: continuing experience and evolution.

The surgical technique for creation of the Mainz pouch uses 10 to 15 cm. of cecum and ascending colon and 2 ileal loops of the same length for construction of a urinary reservoir. Initial applications of the Mainz pouch were for bladder augmentation after subtotal cystectomy and for continent urinary diversion. Current indications have been extended to complete bladder substitution after radical cystoprostatectomy with anastomosis of the pouch to the membranous urethra. For cosmetic reasons the umbilicus is used as a stomal site for continent urinary diversion, and the technique of intussuscepting the continence nipple has been modified accordingly. A total of 100 patients underwent a Mainz pouch procedure since 1983: 34 for bladder augmentation, 15 for total bladder substitution after cystoprostatectomy and 51 for continent urinary diversion. In the bladder augmentation group 1 patient underwent conversion to a continent stoma, 1 has urge and frequency, and the remaining 32 are completely dry day and night. These patients empty the bladder at normal intervals spontaneously except for 3 who rely on intermittent catheterization. In the bladder substitution group 1 patient has grade 1 stress incontinence and the remainder are completely dry during the day. However, at night 4 patients have leakage and they use a condom urinal. In the urinary diversion group all but 2 patients are completely dry and are on intermittent catheterization. The main problem of the initial series was prolapse of the continence nipple, which has been solved by staple fixation of the nipple to the bowel wall and to the ileocecal valve.

Adolescent↗

Evolution of the continuity equation in the Doppler echocardiographic assessment of the severity of valvular aortic stenosis.

The use of Doppler techniques has greatly enhanced the noninvasive ultrasound technique for evaluation of valvular aortic stenosis. M-mode and two-dimensional echocardiography could not reliably distinguish patients with severe aortic stenosis from those with milder obstructions. The hemodynamic information offered by Doppler complemented echocardiographic imaging and provided an alternative modality for evaluation of patients with aortic stenosis. By application of the modified Bernoulli equation, the pressure gradient across the stenotic aortic valve could be estimated by Doppler echocardiography. Though helpful and widely used, the information provided by the pressure gradient across the valve about the severity of the obstruction was not complete. The assessment of valvular aortic stenosis therefore includes an estimation of the valve area by application of the continuity equation. This review examines the maturation of the continuity equation by Doppler techniques and discusses the implications of the procedure.

Aortic Valve Stenosis↗

The pediatric intern retreat: 20-year evolution of a continuing investment.

For the past 22 years the interns in pediatrics at the University of Washington and Children's Hospital and Regional Medical Center have been relieved of all clinical duties in order to participate in a five-day retreat. The retreat provides an opportunity for the interns to learn more about their classmates, build stronger bonds, and provide mutual support. This retreat has been supported by the hospital, the department of pediatrics, faculty, fellows, and community physicians. The authors describe the history of the Intern Retreat, present its goals, daily activities, and faculty, and discuss how the retreat is funded and supported by the hospital and the medical community.

Humans↗

Organizational change in the Medical Library Association: evolution of the continuing education program.

"Change" is a critical dimension of contemporary experience. Library associations are not exempt, and they change in ways similar to other organizations. According to some authorities, four phases typify the process: diagnosis, design, implementation, and incorporation. Focusing on changes in the Medical Library Association's longstanding program of continuing education, the authors utilize the "phase framework" to chart that association's movement from a management system depending primarily upon volunteers to one in which professional staff figure prominently. The historical review serves a heuristic purpose for individuals and institutions in identifying characteristic features of the change process.

Education, Continuing↗

[The application of evoked potentials to the evolutive control of continuous spike/wave epilepsy during slow wave sleep].

We studied 4 patients (14-21 years old) with continuous spike/wave epilepsy during slow wave sleep with visual evoked potentials (VEP) and somatosensory evoked potentials (SEP). All the patients presented the same focality and received the same medication (primidone plus sodium valproate). No case had another pathology not related with epilepsy which could alter the evoked potential findings. The results obtained in the initial evoked potentials were compared with those achieved after 5 years of treatment. In the initial study interhemispheric asymmetry in the latency of the early component (L.N1) of the SEP was observed with a mean of 10%. Five years later normal SEP were obtained with the asymmetry having disappeared thus leading to the deduction that the physiopathologic improvement found in these patients was due to the treatment of sodium valproate together with primidone.

Adolescent↗