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Characterization of the transit and transition times for a pathway unit of Michaelis-Menten mechanism.

The transit time and a characteristic time constant for the transition time are formulated for a pathway unit of Michaelis-Menten mechanism in metabolic chains with mass-action-type dependence. The pathway unit in a chain is assigned to each metabolite and two consecutive Michaelis-Menten-type reactions associated with it. All the relevant functions such as control coefficients, elasticities and transit time for the pathway unit are expressed in terms of the flux J and other system parameters. The transition time is characterized by a time constant for a first-order system expressed as the derivative of the total concentration of the internal metabolite with respect to the flux J.

Computer Simulation↗

Phase transitions and criticality in small systems: vapor-liquid transition in nanoscale spherical cavities.

Phase transformations in fluids confined to nanoscale pores, which demonstrate characteristic signatures of first-order phase transitions, have been extensively documented in experiments and molecular simulations. They are characterized by a pronounced hysteresis, which disappears above a certain temperature. A rigorous interpretation of these observations represents a fundamental problem from the point of view of statistical mechanics. Nanoscale systems are essentially small, finite volume systems, in which the concept of the thermodynamic limit is no longer valid, and the statistical ensembles are not equivalent. Here, we present a rigorous approach to the description and molecular simulations of phase transitions and criticality in small confined systems, as illustrated by the example of vapor-liquid transition (capillary condensation) in spherical cavities. The method is based on the analysis of the canonical ensemble isotherms, which can be generated by the gauge cell Monte Carlo simulation method. The method allows one to define the critical temperature of phase transition, conditions of phase equilibrium, limits of stability of metastable states, and nucleation barriers, which determine hysteretic phase transformations.

Journal Article↗

Phase transitions of a polymer threading a membrane coupled to coil-globule transitions.

We theoretically study phase transitions of a polymer threading through a pore imbedded in a membrane. We focus on the coupling between a partition of the polymer segments through the membrane and a coil-globule transition of the single polymer chain. Based on the Flory model for collapse transitions of a polymer chain, we calculate the fraction of polymer segments and the expansion factor of a polymer coil on each side of the membrane. We predict a first-order phase transition of a polymer threading a membrane; polymer segments in one side are discontinuously translocated into the other side, depending on solvent conditions and molecular weight of the polymer. We also discuss the equilibrium conformation of the polymer chain on each side of the membrane.

Journal Article↗

Medium-induced radiationless transitions and effect of solvent on radiationless transitions.

The purpose of this paper has been to investigate the effect of solvent on radiationless transitions. Two types of the solvent effect have been studied: one is the so-called medium-induced radiationless transition, i.e., the radiationless transition induced by the interaction between the solute and solvent, and the other is the effect of solvent on the radiationless transition through the change in energy gap induced by the solute-solvent interaction.

Journal Article↗

Scaling and transition structure dependence on the fluid viscosity ratio in the selective withdrawal transition.

In the selective withdrawal experiment, fluid is withdrawn through a tube with its tip suspended above a two-fluid interface. At sufficiently high flow rates, the interface undergoes a transition so that the lower fluid is entrained with the upper one, forming a spout. Previous experiments address the scalings and similarity profiles characterizing steady states of the system near the transition for one combination of fluids. In the present study, we show that these scalings and similarity profiles extend to systems with different viscosity ratios. Surprisingly, we find no dependence of the scalings and similarity profiles on the lower fluid viscosity. We use the results of a low-Reynolds-number flow dimensional analysis to show that for different fluid combinations the curves denoting the transition straw height as a function of flow rate can be collapsed. Finally, these results are used to argue that in the low-Reynolds-number regime, the capillary length sets the scale for the final curvature of the interface before the transition.

Journal Article↗

Estimating transition probabilities from aggregate samples plus partial transition data.

Longitudinal studies often collect only aggregate data, which allows only inefficient transition probability estimates. Barring enormous aggregate samples, improving the efficiency of transition probability estimates seems to be impossible without additional partial-transition data. This paper discusses several sampling plans that collect data of both types, as well as a methodology that combines them into efficient estimates of transition probabilities. The method handles both fixed and time-dependent categorical covariates and requires no assumptions (e.g., time homogeneity, Markov) about the population evolution.

Acquired Immunodeficiency Syndrome↗

Multiple-transition cell cycle models that exhibit transition probability kinetics.

Cell cycle models that allow multiple random transitions and asymmetric cell division may exhibit a property that has been used to support the transition probability model of the cell cycle: that the absolute value of the difference between sibling cell inter-mitotic times varies from one sibling pair to another and is described by an exponential statistical distribution. Three models that show this property are described, each of which postulates the existence of objects that are partitioned between daughter cells during cell division and whose number influences the duration of the subsequent cell cycle, e.g., surface receptors for growth factors or transcriptional complexes that are carried by sister chromatids. In the first model, sibling cells receive identical numbers of the objects, which are used to perform multiple random transitions that constitute part of the cell cycle. The second model is like the first, except that the partitioning of objects between the newly-formed sibling cells is random. The third model is also like the first, except that all of the objects are passed to one of the sibling cells. These results show that the general mechanisms that are responsible for the dispersion of inter-mitotic times, the correlation between sibling generation times and the apparently exponentially distributed difference between sibling generation times, could be a combination of unequal cell division, multiple random cell cycle transitions and heterogeneity of mitotic cells.

Cell Cycle↗

Transitional object and children with chronic disease. Comparative study of the forms of transitional object among children with diabetes mellitus or rheumatic disease.

The prevalence of the transitional object among children with rheumatic disease and diabetes mellitus is examined in this comparative study with highly matched groups. There is no evidence which could indicate the lack of transitional objects among these children. In the rheumatic group the transitional object was more common than in the other groups and the children used it later than others. The soothing function of transitional object is discussed.

Adaptation, Psychological↗

Community transition teams as the foundation for transition services for youth with learning disabilities.

This article synthesizes descriptions of and recommendations for community transition teams found in research articles, model project reports, and state department documents. The levels, composition, and functions of transition teams are described. Community-level transition teams are shown to be critical support vehicles for helping communities improve their transition programs for youth and adults with learning or other disabilities. Highlights of the changes generated by community teams illustrate their potential impact; the experiences of team members illustrate the challenges to which future efforts need to respond.

Education, Special↗

Randomised controlled trial of early detection and cognitive therapy for preventing transition to psychosis in high-risk individuals. Study design and interim analysis of transition rate and psychological risk factors.

BACKGROUND: There is interest in the possibility of indicated prevention of psychosis. There is a strong case for using psychological approaches to prevent transition to psychosis in high-risk patients. AIMS: To identify individuals at high risk of transition to psychosis, and psychological characteristics relevant to the development of psychosis in this group. METHOD: The design of a randomised controlled trial of cognitive therapy for the prevention of psychosis in people at high risk (meeting operational criteria of brief or attenuated psychotic symptoms, or first-degree family history with functional decline) is outlined. The first patients recruited are compared with non-patient samples on cognitive and personality factors; an interim analysis of transition rate is reported. RESULTS: Cases (n = 31) were recruited mainly from primary care. Of the 23 high-risk patients monitored for 6-12 months, 5 (22%) made the transition to psychosis. The high-risk group scored significantly higher than non-patients on measures of schizotypy, metacognitive beliefs and dysfunctional self-schemas (sociotropy). CONCLUSIONS: The findings validate the methods of identifying individuals at high risk of experiencing a psychotic episode. Compared with non-patient controls, the cases showed dysfunctional metacognitive beliefs and self-schemas.

Adult↗

Lost in transition: challenges and opportunities for improving the quality of transitional care.

Transitional care has been defined as a set of actions designed to ensure the coordination and continuity of health care as patients transfer between different locations or different levels of care in the same location. Transitional care, which primarily concerns the relatively brief time interval that begins with preparing a patient to leave one setting and concludes when the patient is received in the next setting, poses challenges that distinguish it from other types of care. Many transitions are unplanned, result from unanticipated medical problems, occur in "real time" during nights and on weekends, involve clinicians who may not have an ongoing relationship with the patient, and happen so quickly that formal and informal support mechanisms cannot respond in a timely manner. This article describes the challenges involved in and potential solutions for improving the quality of transitional care.

Continuity of Patient Care↗

Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans.

Colonic transit scintigraphy was developed to quantitatively evaluate colonic transit. Using this technique the progression of a radiolabeled marker from cecal instillation to defecation was studied in 7 normal male volunteers. An 8-ml bolus containing 50 mu Ci of indium 111-diethylene triamine pentaacetic acid was instilled into the cecum via a 2-mm tube, which was passed orally, and serial scintigrams were obtained over 48 h. By 48 h, 70.7% +/- 9.1% (mean +/- SEM) of the instilled activity had been defecated. The cecum and ascending colon emptied rapidly, with a half-emptying time of 87.6 +/- 27.0 min. Geometric center analysis showed an initial logarithmic progression of activity in the proximal colon and a linear progression distally. This study suggests that the transverse colon, not the cecum and ascending colon, may be the primary site for fecal storage. Colonic transit scintigraphy is a safe, physiologic, and quantitative method for evaluating the colonic transit of fecal material and may provide a useful tool for evaluating normal and abnormal large intestinal physiology.

Adult↗

Effects of adenine tracts on the B-Z transition. Fine tuning of DNA conformational transition processes.

The effects exerted by short runs of adenines (A-tracts), alternating (AT)n segments, and single-stranded DNA upon the right- to left-handed DNA transition, as well as upon the energetic and structural parameters of the B/Z junctions, were investigated by using synthetic segments in which these motifs are coupled to a potentially Z-forming core. UV, CD, and 31P NMR studies of the salt-induced B to Z transition occurring in the various segments indicate that the transition is composed of two phases: a slow rate-determining induction of an initial structural deformation followed by a cooperative propagation of this "nucleus" in the form of a left-handed Z-DNA. The first phase is found to be crucially affected by the nature of the sequences coupled to the potentially Z-forming core. Thus, a higher rigidity of the flanking segments, such as that characterizing adenine tracts, is associated with higher energy values required for the induction of the initial conformational deformation, as well as with more defined structural parameters of the ultimate B/Z junctions. The second phase is affected mainly by the composition and sequence of the Z-forming segment. The observations that DNA conformational changes can be finely tuned and modulated by parameters pertaining to both the segment which undergoes the transition and the flanking sequences support the notion that DNA secondary motifs, such as the Z form and A-tracts, might be involved in the regulation of cellular processes.

Adenine↗

The transition to extrauterine life and disorders of transition.

With shorter postnatal hospital stays, concern has arisen that many infants may be discharged prior to completion of the transition to extrauterine life, a time of dynamic physiologic change when many neonatal problems may present. This article reviews the physiology of the neonatal transition together with common transitional disorders. Most disorders of transition present at typical postnatal time periods, permitting their timely anticipation and treatment. Moreover, many are associated with factors that may further aid the clinician in defining those infants at highest risk.

Humans↗

Glass transition-related changes in molecular mobility below glass transition temperature of freeze-dried formulations, as measured by dielectric spectroscopy and solid state nuclear magnetic resonance.

The purpose of this study was to explore why changes in the molecular mobility associated with glass transition, the timescale of which is on the order of 100 s, can be detected by measuring the nuclear magnetic resonance relaxation times that reflect molecular motions on the order of 10 kHz and 1 MHz. The molecular motions in freeze-dried dextran 40k, dextran 1k, isomaltotriose (IMT), and alpha-glucose comprising a common unit but with different glass transition temperatures, were investigated by dielectric spectroscopy (DES) in the frequency range of 0.01 Hz to 100 kHz and in the temperature range of -20 degrees to 200 degrees C, in order to compare with the molecular motions reflected in nuclear magnetic resonance relaxation times. The alpha-relaxation process for freeze-dried alpha-glucose was visualized by DES, whereas those for freeze-dried dextran 40k, dextran 1k, and IMT were too slow to be visualized by DES. The latter freeze-dried cakes exhibited quasi-dc polarization because of proton-hopping-like motion rather than alpha-relaxation process. The correlation time (tau(c)) for the backbone carbon of dextran 40k and IMT, calculated from the measured value of spin-lattice relaxation time in the rotating frame, was found to be close to the relaxation time of proton-hopping-like motion determined by DES (tau(DES)) at temperatures around glass transition temperature. The timescales of molecular motions reflected in the tau(c) and tau(DES) were significantly smaller than that of motions leading to molecular rearrangement (molecular rearrangement motions), which correspond to alpha-relaxation. However, the shapes of temperature dependence for the tau(c) and tau(DES) were similar to that of the calorimetrically determined relaxation time of molecular rearrangement motions. Results suggest that the molecular motions reflected in the tau(c) and tau(DES) are linked to molecular rearrangement motions, such that enhancement of molecular rearrangement motions enhances the molecular motions reflected in the tau(c) and tau(DES). Thus, the tau(DES) and tau(c) can reflect changes in molecular mobility leading to unwanted changes in amorphous formulations, and are thought to be a useful measure for evaluating the stability of formulations.

Dextrans↗

Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium.

OBJECTIVES: Multifocality of transitional cell carcinoma (TCC) has been attributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been shown to evolve as a consequence of genetic defects and chromosomal instability. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship to the development of multifocal TCC. METHODS: Included in the study were 47 patients, 16 women and 31 men, with a mean age of 70.04 years (range 37 to 83). Of 47 patients, 45 had TCC of the urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluorescence in situ hybridization, numerical aberrations of chromosomes 7, 9, and 17 were detected in imprint specimens of histologically verified tumor and "normal" urothelium and were compared with static ploidy and p53 and Ki67 expression. RESULTS: Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (including monosomy), and chromosome 17 in 87.2% of the 47 analyzed tumor and normal imprints. Differences between tumor and normal epithelium were observed in aberrational frequencies (number of cells showing chromosomal aberrations calculated on 200 cells counted, given in percentages). DNA content was aneuploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal specimens, according to lower aberration frequencies in these patients. p53 detection was positive in 82.9% of the tumor specimens and 76.6% of the normal specimens. Ki67 was positive in 87.2% of the tumor imprints and in 72.3% of the normal specimens. CONCLUSIONS: These data suggest a general genetic instability as a reason for multifocality in the entire transitional epithelium.

Adult↗

Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates small bowel transit.

UNLABELLED: The lactulose breath test (LBT) and gastroenterocolonic scintigraphy (GECS) can both be used to measure orocecal transit time (OCTT). The aims of this study were (1) to measure OCTT by LBT and GECS and (2) to determine whether lactulose alters orocecal transit. METHODS: Eight normal subjects underwent simultaneous breath hydrogen testing, GECS, and duodenal manometry while receiving either 10 g lactulose or placebo with a radiolabeled solid/liquid test meal during two studies. There was a good correlation between OCTT by LBT and GECS when performed simultaneously (r = 0.95; P < 0.001). OCTT by GECS with lactulose was significantly faster (P = 0.004) than by GECS without lactulose, despite no change in gastric emptying of liquids and slowing of gastric emptying of solids (P = 0.02). The postprandial duodenal motility index was greater with lactulose than with placebo (P = 0.031). This study demonstrates that LBT and GECS (without lactulose) are not equivalent measures of OCTT. The standard LBT accelerates OCTT and slows gastric emptying. Therefore, lactulose has a direct accelerating effect on small intestinal transit.

Adult↗

Transitional cell carcinomas of the urinary bladder that may be underdiagnosed. A report of four invasive cases exemplifying the homology between neoplastic and non-neoplastic transitional cell lesions.

Four unusual invasive transitional carcinomas of the urinary bladder arose in patients aged 70 to 85 years. One or more specimens from each case were misinterpreted as benign. The features that led to diagnostic confusion included nests and trabeculae composed of cells with relatively bland cytologic features and small tubules, medium-sized glands, or cysts that suggested nephrogenic adenoma, cystitis glandularis, or cystitis cystica. In three cases, elongated slit-like lumens or clefts that frequently branched were also present, and several tumors had nests with pointed projections from which neoplastic cells invaded into the adjacent stroma in an often inconspicuous manner. In addition to their unusual patterns and frequent deceptive cytologic features, the tumors were noteworthy because they often had cells with abundant eosinophilic cytoplasm. A variety of architectural features, specifically a disorderly distribution of the epithelial elements, their frequent packed arrangement, and their variation in size and shape, all spoke for a neoplastic interpretation in the current cases. Additionally, in most of these cases, small clusters of cells or individual cells of more conventional invasive carcinoma facilitated the interpretation. The results of the study of these four cases expand the spectrum of recently described peculiar features of transitional cell carcinoma of the urinary bladder. Several of the findings in these tumors exemplify the parallels that exist between nonneoplastic epithelial abnormalities and transitional cell carcinoma of the bladder.

Aged↗