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Results for “Model explainability”

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PubMed2004

Coulomb explosion of large polyatomic molecules assisted by nonadiabatic charge localization.

The electron-nuclear dynamics of the Coulomb explosion of a large polyatomic molecule, anthracene, is probed using kinetic energy distributions of produced H+ ions. The kinetic energy release of ejected protons exceeds 30 eV for anthracene exposed to 10(14) W cm(-2), 800 nm pulses of 60 fs duration. We propose a strong-field charge localization model, based on nonadiabatic dynamics of charge distribution in a (multiply) ionized molecule; the charge localization lasts many laser periods and is sustained through successive ionizations of the molecular ion. The model explains quantitatively the dependence of the H+ kinetic energy on the laser intensity. Dissociative ionization of a polyatomic molecule enabled by long-lived charge localization is a new type of electron-nuclear dynamics and is essential for understanding the pathways of molecular or ionic fragmentation in strong fields.

Journal Article↗

PubMed2005

Measuring the kernel of time-dependent density functional theory with x-ray absorption spectroscopy of transition metals.

The 2p-3d core-hole interaction in the L2.3 absorption spectra of the transition metals is treated within time-dependent density functional theory. A simple three-level model explains the origin of the strong deviations from the one-particle branching ratio and yields matrix elements of the unknown exchange-correlation kernel directly from experiment.

Journal Article↗

PubMed2006

Propulsion of ripples on glass by ion bombardment.

The propulsion of surface ripples on SiO(2) by an ion beam was investigated by in situ electron microscopy. The observed propagation of the ripples contradicts existing models for ion-beam-induced ripple development. A new model based on the Navier-Stokes relations for viscous flow in a thin layer is introduced. It includes inhomogeneous viscous flow, driven by spatial variations in the deposition of the energy of the ion beam. The model explains the observed reversed propagation. The hitherto unknown propulsion mechanism is important for understanding nanoscale pattern formation by ion bombardment.

Journal Article↗

PubMed1975

The Interaction between Osmotic- and Pressure-induced Water Flow in Plant Roots.

This paper presents a general model for coupled solute and water flow through plant roots based on the thermodynamics of irreversible processes. The model explains in a straight-forward manner such experimentally observed phenomena as changes in root resistance, increased solute flux, and apparent negative resistance, which have been reported for root systems under the influence of a hydrostatic pressure gradient. These apparent anomalies are explained on the basis of the interaction between the osmotic and hydrostatic driving forces and the well known "sweeping away" or dilution effect. We show that with a constant hydraulic conductivity the only features necessary to explain these phenomena are some type of membrane or membranelike structure and a mechanism for actively accumulating solutes.

Journal Article↗

PubMed1996

1-trityl-4-nitroimidazole.

X-ray analysis confirmed the configuration of the title N1-alkylated C4-nitroimidazole inhibitor. The plane of the imidazole ring, sitting on an axis of the trityl propeller, bisects the angle between two phenyl rings, while the nitro group extends over the third. Modeling of the interactions between the cytochrome P450 and the title compound (C22H17N3O2) has been performed on the basis of the crystal structures of 1-trityl-4-nitroimidazole and bacterial cytochrome P450BM-3. The replacements and deletions in the sequence of the latter has been performed to match mammalian cytochrome P450-IIIA1. The modeling explained why inhibitors with a C4-substituted imidazole ring showed lower effectivity than those without substituents, as an additional group of atoms at C4 prevents close interactions of the imidazole ring with the heme Fe atom.

Antifungal Agents↗

PubMed2000

Salient value similarity, social trust, and risk/benefit perception

It was postulated that shared values determine social trust in institutions and persons related to a technology: One has trust in people holding similar salient values. Furthermore, it was hypothesized that social trust has a positive influence on perceived benefits and a negative impact on perceived risks. Results of a survey of University of Zurich students indicated that the proposed causal model explained perception of pesticides, nuclear power, and artificial sweetener very well. When social trust was controlled, the relation between risks and benefits perceived diminished. Results indicate that social trust is a key predictive factor of the perceived risks and benefits of a technology, and provide support for the salient values similarity theory of social trust.

Journal Article↗

PubMed2026

Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.

Cell division inevitably shortens telomeric DNA owing to the end-replication problem. Eukaryotic chromosomes possess specialized telomere structures to maintain genomic stability. In most proliferative cells, telomerase adds telomeric repeats during S-phase. In differentiated cells where telomerase is silenced, telomeres shorten progressively, thereby compromising genomic integrity. Consequently, cancer cells universally activate alternative telomere maintenance mechanisms during malignant transformation: ~80% reactivate telomerase, while a portion of the rest rely on BIR (break-induced replication)-mediated homologous recombination-based ALT (alternative lengthening of telomeres). Although these mechanisms are stable once established, the initial determinants influencing a cancer cell's choice remain poorly understood. This review discusses recent molecular insights into how telomeric chromatin properties profoundly impact this choice. After briefly introducing telomere chromatin characteristics and key players in its maintenance and dynamics, we discuss the mechanisms by which cancer cells acquire distinct telomere replication capabilities. In particular, we present an in-depth analysis linking telomere heterochromatin status to ALT. Furthermore, based on recent advances, we propose a coupled feedforward loop model explaining how the ALT state becomes "locked in" once initiated. Finally, we offer novel perspectives on rational, telomere-centric therapeutic interventions for ALT-positive cancers, focusing on strategies designed to disrupt such feedforward loops by manipulating telomeric chromatin structure.

Humans↗

PubMed2002

A cost of restoration of male fertility in a gynodioecious species, Lobelia siphilitica.

Models allowing the coexistence of females and hermaphrodites in gynodioecious populations assume a simple genetic system of sex determination, a seed fitness advantage of females (compensation), and a negative pleiotropic effect of nuclear sex-determining genes on fitness (cost of restoration). In Lobelia siphilitica, sex is determined by both mitochondrial genes causing cytoplasmic male sterility (CMS) and nuclear genes that restore fertility when present with specific CMS haplotypes (nuclear restorers). I tested for a cost of restoration in L. siphilitica by measuring restored hermaphrodites for five fitness components and estimating the number of nuclear restorers by crosses with females carrying CMS1 and CMS2. A cost of restoration appears as a significant negative coefficient (B) in the regression model explaining fitness. I found that hermaphrodites carrying more nuclear restorer genes for CMS2 (or restorer genes of greater effect) have lower pollen viability (B = -1.08, P = 0.001). This pollen viability cost of restoration in L. siphilitica supports the theoretical prediction that negative pleiotropic effects of restorers will exist in populations of gynodioecious species containing females. The existence of such a cost supports the view that gynodioecy can be a stable breeding system in nature.

Fertility↗

PubMed1983

Serum HDL cholesterol in a high coronary risk population in eastern Finland.

The serum high density lipoprotein (HDL) and total cholesterol levels and their determinants were explored in a random population sample from eastern Finland, an area with an exceptionally high mortality and morbidity from coronary heart disease (CHD). A total of 1792 persons aged 14-65 years were studied. Serum HDL cholesterol was determined in one series by using an enzymatic method after precipitation by dextran-magnesium chloride. The mean serum HDL cholesterol was 1.41 mmol/l in men and 1.62 mmol/l in women. Although a multivariate linear regression model explained 21% (for men) and 28% (for women) of the variation in serum total cholesterol, the same variables were able to account for only 9 and 4%, respectively, of the variation in serum HDL cholesterol. Among men, obesity and the daily consumption of tobacco products were inversely associated and the weekly consumption of beer and age were directly associated with serum HDL cholesterol and the serum HDL cholesterol/total cholesterol ratio.

Adolescent↗

PubMed1991

Tobacco advertising restrictions, price, income and tobacco consumption in OECD countries, 1960-1986.

Factors affecting tobacco consumption per adult in 22 countries of the OECD between 1960 and 1986, were studied using pooled cross-section time-series analysis. The resulting log-linear model was estimated using Generalized Least Squares. The severity of tobacco advertising restrictions in each country and year was scored from published legislation and information from health agencies. Tobacco advertising restrictions have since 1973 increasingly been associated with lower tobacco consumption. Lower consumption levels were also associated with higher real tobacco prices, and with increased female labour force participation. Higher levels of consumption were associated with higher per capita real income and with a larger fraction of tobacco consumed as manufactured cigarettes. The model explains 99.5% of the variance in the average annual level of tobacco consumption across these countries. Ten-fold differences in purchasing power for tobacco products were found across the countries and years studied. In all countries tobacco products became more affordable between 1960 and 1986. In 1986 either a 36% inflation-indexed increase in real tobacco prices, or legislation to end tobacco promotion in those countries without a total ban, would have lowered average consumption by 6.8% and both together, by 13.5%. Across the OECD, if in 1986 all governments had raised tobacco product prices relative to income to Irish levels, and had banned all tobacco promotion, tobacco products consumption per adult would have fallen by 40% in that year.

Advertising↗

PubMed2007

A comparative multi-level analysis of contextual drinking in American and Canadian adults.

AIM: To investigate the effects of demographic factors and drinking location on contextual drinking in a comparison of US and Canadian adults. DESIGN: Multi-level techniques were used to model the two-level hierarchical structure of drinking contexts (level 1) nested within individuals (level 2). PARTICIPANTS: Two random samples of current drinkers aged 18 years or older were drawn from Canada's Alcohol and Other Drugs Survey (CADS, 1994) and the 1995 National Alcohol Survey (NAS 9). The US sample included 2304 respondents (level 2) who reported a total of 5956 drinking contexts (level 1); in Canada, 5394 respondents reported 13 235 drinking contexts. MEASUREMENTS: Participants reported usual alcohol intake in up to four drinking locations. Demographic data included age, gender, education level, income and marital status. FINDINGS: Significant variation in usual alcohol intake was observed between drinking locations in both the US and Canada. The full multi-level models explained 25% of the variance at the contextual level and 25% and 22% at the individual level in the US and Canada. Contextual drinking was determined by a complex relationship between demographic characteristics and drinking locations. Some interactions between locations and demographic variables were observed for both the US and Canada, whereas others were observed only in the US sample. CONCLUSIONS: There is a need, from a population health perspective, for a multi-level approach in epidemiology and prevention that considers drinking setting as a relevant level for analysis and intervention.

Adult↗

PubMed2005

Clinical correlates of steady-state oxyhaemoglobin desaturation in children who have sickle cell disease.

Individuals with sickle cell disease (SCD) may have oxyhaemoglobin desaturation during the steady-state, the causes of which are incompletely known. We studied a cohort of 585 children who have sickle cell anaemia (SS), sickle beta0-thalassaemia (Sbeta0), sickle-haemoglobin C disease (SC), or sickle beta+-thalassaemia (Sbeta+) to determine the relationships between steady-state oxyhaemoglobin saturation (SpO2) and SCD genotype, age, gender, steady-state haemoglobin (Hb) and reticulocyte count, and rate of acute chest syndrome (ACS). The SS/Sbeta0 group (n = 390) had lower mean SpO2 than the SC/Sbeta+ group (n = 195) (96.3% vs. 98.7%, P < 0.001). Among SS/Sbeta0 subjects, a decrease in steady-state SpO2 correlated with a decrease in Hb, an increase in reticulocytes, older age and male gender. These correlations were not found in the SC/Sbeta+ group. Prior ACS did not correlate with steady-state SpO2. A multivariate model explained 45% of the variability in SpO2, but only 5% of the variation in SpO2 was explained by Hb. We conclude that steady-state desaturation is common in individuals with SCD, but it appears to be unrelated to prior episodes of ACS and largely unexplained by chronic anaemia.

Adolescent↗

PubMed2004

The smell map: commonality of odour perception confirmed.

We have examined the repeatability of a perceptual space, or smell map, initially developed in a sample of 20 people. A total of 110 normosmic people performed similarity ratings for pairs of the 11 commonly encountered odours used in the previous study. Multidimensional scaling was again used to analyse the relationships between odours. Some individual plots and an archetype, generated using the data from all participants, produced results similar to the previous study, confirming the ability to obtain reproducible results using a different tester and different participants. Exploration of the source space, that is, the spatial distribution of the individual plots relative to each other, suggests that the current model explains about 50% of the variation between subjects for the two-dimensional solution and 57% for the three-dimensional solution.

Adolescent↗

PubMed1990

Mechanism of polysialic acid chain elongation in Escherichia coli K1.

Understanding the mechanisms of polysialic acid synthesis in Escherichia coli K1 requires a molecular description of the polymerase complex. Since the number of potential models explaining polysialic acid assembly would be constrained if only one sialyltransferase were required for this process, the phenotypes of a sialyltransferase null mutation generated by transposon mutagenesis were investigated. The chromosomal insertion mutation was mapped by Southern hybridization analysis and by complementation with plasmid subclones, demonstrating that sialyltransferase is encoded by neuS, a gene implicated previously as coding for the polymerase (Vimr et al., 1989). As expected, if only one gene encoded sialyltransferase, the null mutant had undetectable polymerase activity when assayed with endogenous or exogenous acceptors, and accumulated sugar nucleotide precursors intracellularly. Nested deletion analysis of neuS ruled out polarity effects of transposon insertion mutation and provided more precise mapping of the sialyltransferase structural gene. Maxicell analysis of the nested deletion set implicated a 34,000 molecular weight polypeptide as the neuS gene product. These results, together with biochemical characterization of sialyltransferase reaction products in the wild type, indicated that CMP-sialic acid is the probable sialosyl donor for polysialic acid elongation and that chain growth is by sequential addition of monomeric units.

Blotting, Southern↗

PubMed1995

Deletion analysis of gene minE which encodes the topological specificity factor of cell division in Escherichia coli.

Division inhibition caused by the minCD gene products of Escherichia coli is suppressed specifically at mid-cell by MinE protein expressed at physiological levels. Excess MinE allows division to take place also at the poles, leading to a minicell-forming (Min-) phenotype. In order to investigate the basis of this topological specificity, we have analysed the ability of truncated derivatives of MinE to suppress either minCD-dependent division inhibition in a chromosomal delta(minB) background, or the division inhibition exerted by MinCD at the cell poles in a minB+ strain. Our results indicate that these two effects are not mediated by identical interactions of MinE protein. In addition, gel filtration and the yeast two-hybrid system indicated that MinE interacts with itself by means of its central segment. Taken together, our results favour a model in which wild-type MinE dimer molecules direct the division inhibitor molecules to the cell poles, thus preventing polar divisions and allowing non-polar sites to divide. This model explains how excess MinE, or an excess of certain MinE derivatives which prevent the accumulation of the division inhibitor at the poles, can confer a Min- phenotype in a minB+ strain.

Amino Acid Sequence↗

PubMed2005

Cell cycle-regulated degradation of tmRNA is controlled by RNase R and SmpB.

The production and removal of regulatory RNAs must be controlled to ensure proper physiological responses. SsrA RNA (tmRNA), a regulatory RNA conserved in all bacteria, is cell cycle regulated and is important for control of cell cycle progression in Caulobacter crescentus. We report that RNase R, a highly conserved 3' to 5' exoribonuclease, is required for the selective degradation of SsrA RNA in stalked cells. Purified RNase R degrades SsrA RNA in vitro, and is kinetically competent to account for all SsrA RNA turnover. SmpB, a tmRNA-binding protein, protects SsrA RNA from RNase R degradation in vitro, and the levels of SmpB protein during the cell cycle correlate with SsrA RNA stability. These results suggest that SmpB binding controls the timing of SsrA RNA degradation by RNase R. We propose a model for the regulated degradation of SsrA RNA in which RNase R degrades SsrA RNA from a non-tRNA-like 3' end, and SmpB specifically protects SsrA RNA from RNase R. This model explains the regulation of SsrA RNA in other bacteria, and suggests that a highly conserved regulatory mechanism controls SsrA activity.

Caulobacter crescentus↗

PubMed1982

The protein component(s) of the isolated phosphate-transport system of mitochondria.

The ethylmaleimide-sensitive phosphate-transport system of heart mitochondria was isolated and the activity reconstituted in liposomes. The identification of the phosphate-carrier protein was complicated by several factors. 1. The phosphate-carrier fraction, isolated through different procedures in different laboratories, contains 4-5 protein components of very similar apparent molecular weight, as shown by gradient dodecylsulfate gel electrophoresis. 2. The amino acid composition of protein 1, 2 and 3(apparent Mr = 34 500, 34 000 and 33 000, respectively) is quite similar although not identical. 3. Including several protease inhibitors during isolation of the phosphate-carrier fraction does not influence the protein pattern. 4. Labeled N-ethylmaleimide binds only protein 1 and 3, labeled N,N'-dicyclohexylcarbodiimide bonds only to protein 1 and 2. 5. N,N'-Dicyclohexylcarbodiimide had no effect on the reconstituted phosphate-exchange activity after incubation with intact mitochondria or proteoliposomes. 6. In the presence of protecting mersalyl concentrations N-ethylmaleimide inhibits the phosphate transport in intact mitochondria. Under these conditions no label ethylmaleimide was bound to the phosphate-carrier fraction. 7. Comparison of the reconstituted transport activity with the protein pattern of fractions, isolated with or without cardiolipin, shows correlation of transport with the amount of protein 2 but not with that of protein 1, which binds ethylmaleimide. A model of the mitochondrial phosphate carrier is presented which suggests a proteolytic degradation of the phosphate-carrier protein during its isolation. The model explains the contradictory results of this investigation.

Adenosine Diphosphate↗

PubMed1984

Characteristic features of an alpha-galactosidase from mung beans.

Two molecular forms, I and II (high and low molecular mass) of alpha-galactosidase were demonstrated in dry mung beans and a multi-step procedure was developed for isolating the tetrameric enzyme I in good yield. Two affinity chromatographic techniques were employed and an overall 10 000-fold purification was achieved. The enzyme was able to catalyse the hydrolysis of alpha-galactosidic linkages as well as agglutinate rabbit erythrocytes (clot formation). The clot was temporary and dissolved on longer incubation, yielding free galactose. The pH optima for both activities were similar. The enzyme also destroyed human-blood-group-B activity and increased H activity. The effect of pH on Km and Vmcx of the enzyme indicated the importance of carboxyl (pK approximately equal to 4.0) and histidine (pK approximately equal to 6.5) groups for activity. This was confirmed by amino acid modification experiments in the absence and presence of the substrate. The stoichiometry of enzyme inactivation showed the probable presence of 12 carboxyl groups and 9 histidine imidazole groups/molecule enzyme in the active site. The effects of modification of the groups on enzymic and hemagglutinating activities were parallel. A model explaining the display of both the activities by the enzyme, is presented in which hemagglutination is shown to be due to the formation of slightly stable enzyme-substrate complex. It is proposed that a true lectin should not alter the covalent status of the binding sugar.

Amino Acids↗