Rate Change Point Research Articles

Inference for a Hazard Rate Change Point

Inference for a Hazard Rate Change Point

Changes in the activity of alcohol dehydrogenase during the cell cycle of the fission yeast Schizosaccharomyces pombe

ABSTRACT The activity of alcohol dehydrogenase (ADHase) was followed in synchronous cultures of Schizosaccharomyces pombe. In selection synchronised cultures of wild-type cells, it followed a linear pattern in which there was a constant rate of increase of activity followed by a doubling of this rate at the end of the cycle. The same pattern was also found in selection synchronised cells of wee mutants except that the point of rate change was shifted to 0.27 of the cycle. A similar linear pattern was also found in the shortened cell cycles produced by induction synchrony (block and release of the mutant cdc2.33) but the rate change point was at about 0.75 of the cycle. In the mutant cdcl3.117, there was a marked fall in the rate of activity increase at 35°C but not at 37°C. In all these situations, the ADHase activity closely paralleled in pattern and in timing the rate of production of CO2 established in earlier papers. This suggests a coordinate control of the flux through glycolysis and the activity of the last enzyme in the glycolytic pathway in yeast However, an interesting difference indicating a loss of the coordinate control occurred in ‘synchronous’ cultures of cdc2.33 in which small cells had been selected but in which the DNA-division cycle had been blocked by a shift-up to the restrictive temperature. Rate changes both in CO2 production and in ADHase activity continued in these blocked synchronous cultures but the timing was different. With ADHase activity the timing was 15 % greater than that in a normal cell cycle whereas with CO2 production it was 15% less. We suggest that these and other periodic events are subject to independent oscillatory controls in these blocked cultures with timings that differ from each other and from the normal cycle but in the normal cycle the oscillators are all entrained by one or more events of the DNA-division cycle.

Inference for a hazard rate change point

SUMMARY We discuss inference based on the likelihood ratio process for a hazard rate change point. A random change of time scale transforms the empirical process into a Poisson process which enables us to derive large deviation approximations to the significance level of the likelihood ratio test. We derive approximate confidence regions for the change point and joint confidence regions for the change point and size of change. The effect of censorship is also discussed. The methods are illustrated using Stanford heart transplant data, for which the 70 days following the transplant are found to be most critical.

Impact of Changes in Genetic Improvement Programs and Annual Cycles on Holstein Service Sire Merit

Monthly averages of Holstein service sire PD from January 1960 through December 1985 were examined to determine if a relationship existed with changes in evaluation methodology. Monthly average of service sire PD for registered cows from January 1971 through December 1985 suggested three linear periods of increase. Regression of PD on sequential month were significantly different for periods defined by hypothesized points of rate change (January to February 1975 and February to March 1984). Rate change points determined from data corresponded reasonably well to times of methodology changes, which can be attributed to new evaluations and accompanying educational programs. Changes in service sire PD by calendar month also were studied. After adjustment for general trend, PD for service sires of registered cows were slightly lower in December and January and about 20kg lower in June and July than for the highest months. The unexpected bimodal oscillation was nearly the same as for percentage of services that were AI. Apparently, less AI is used in the 2 mo preceding availability of semiannual sire evaluations and in summer months. For a typical 100-cow herd, a dairy producer annually would sacrifice $121 in gross sales, because AI usage was less than in the highest month, February, and $1381 because AI was not used exclusively. Corresponding amounts for the nation would be $12.3million and $140.9million.

Pseudo-exponential growth in length of the fission yeast, Schizosaccharomyces pombe.

The growth patterns of individual cells of the fission yeast (Schizosaccharomyces pombe wild-type cells, strain 972 h-; cells exposed to hydroxyurea; and cdc mutants, 11-123, 2-33) were investigated by time-lapse photomicrography. Wild-type cells showed one, two, or three linear-growth segments followed by a constant-length stage. Cells with two segments were most frequent. Hydroxyurea cells that divided as oversized cells (about three times the birth length) had three linear-growth segments in a cycle. Mutant cdc11-123 cells did not divide but had a constant-length stage separating the cycles; both the first and second cycles consisted of two linear-growth segments, and cells were oversized at the second constant-length stage (about 3.5 times the birth length). Elongating cdc2-33 cells that did not divide and were oversized (about five times the birth length) while under observation, showed four linear-growth segments. Cells of all strains showed 30 to 40% increase in growth rate at the rate-change point and maintained approximate exponential (pseudo-exponential) growth. We conclude that the normal growth pattern of individual fission-yeast cells is the pseudo-exponential pattern.

Growth in cell length in the fission yeast Schizosaccharomyces pombe.

The cylindrical cells of Schizosaccharomyces pombe grow in length by extension at the ends and not the middle. At the beginning of the cell cycle, growth is restricted to the 'old end', which existed in the previous cycle. Later on, the 'new end', formed from the septum, starts to grow at a point in the cycle that we have called NETO ('new end take-off'). Fluorescence microscopy on cells stained with Calcofluor has been used to study NETO in size mutants, in blocked cdc mutants and with different growth temperatures and media. In wild-type cells (strain 972) NETO happens at 0.34 of the cycle with a cell length of 9.5 microns. With size mutants that are smaller at division, NETO takes place at the same size (9.0-9.5 microns) but this is not achieved until later in the cycle. Another control operates in larger size mutants since NETO occurs at the same stage of the cycle (about 0.32) as in wild type but at a larger cell size. This control is probably a requirement to have completed an event in early G2, since most cdc mutant cells blocked before this point in the cycle do not show NETO whereas most of those blocked in late G2 do show it. We conclude that NETO only happens if: (1) the cell length is greater than a critical value of 9.0-9.5 microns; and (2) the cell has traversed the first 0.3-0.35 of the cycle and passed early G2. NETO is delayed in poor media, in which cell size is also reduced. Temperature has little effect on NETO under steady-state conditions, but there is a transient delay for some hours after a temperature shift. NETO is later in another wild-type strain, 132. Time-lapse photomicrography was used to follow the rates of length growth in single cells. Wild-type cells showed two linear segments during the first 75% of the cycle. There was a rate-change point (RCP), coincident with NETO, where the rate of total length extension increased by 35%. This increase was not due simply to the start of new-end growth, since old-end growth slowed down in some cells at the RCP. cdc 11.123 is a mutant in which septation and division is blocked at 35 degrees C but nuclear division continues.(ABSTRACT TRUNCATED AT 400 WORDS)