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[The moss Physcomitrella patens, a new model system for functional genomics].

The potential of moss as a model system to study plant biological process is associated with their relatively simple developmental pattern and the dominance of the haploid gametophyte in the life cycle. The moss Physcomitrella patens exhibits a very high rate of homologous recombination in its nuclear DNA, making gene targeting approaches in this plant as convenient as in yeast or in ES cells of mice. Sharing many biological features with higher plants and having many other advantages, the moss Physcomitrella patens will be an attractive model system for plant biology and functional genome analysis.

Bryopsida↗

Interaction of low frequency electric fields with the nervous system: the retina as a model system.

The retina provides an example of effects, the visually perceived 'phosphenes', being generated in nervous tissue by external electric or magnetic fields of low frequency and intensity. What is known about the cellular mechanisms by which the phosphenes are generated is reviewed, whether they provide useful information for setting limits on the magnitude of induced electric fields to which nervous tissue can be safely exposed is assessed, and some difficulties in translating these values of internal fields into safe values of external electric or magnetic fields are considered.

Animals↗

Thermometric enzyme linked immunosorbent assay in continuous flow system: optimization and evaluation using human serum albumin as a model system.

Thermometric enzyme-linked immunosorbent assay (TELISA) is described. After the procedure of optimization, human serum albumin was assayed using anti-human serum albumin bound to Sepharose CL 4-B in the enzyme thermistor unit and catalase as label on the free antigen. The model system was used for assays down to 10(-13)M and the preparation of immobilized antibodies was used repeatedly up to 100 times. Comparative studies of the TELISA technique with bromocresol green, immunoturbidimetric and rocket immunoelectrophoretic methods were carried out and showed that TELISA could be used as an alternative method.

Catalase↗

Love and anger in romantic relationships: a discrete systems model.

In a study of 124 dating couples, we tested a discrete systems model of the functions of two emotion systems in romantic relationships: love and anger/upset. This model posits that the operation of these systems reflects adaptations shaped by natural selection to solve different adaptive problems. Accordingly, we hypothesized that the love and anger/upset emotion systems would be largely independent in the classes of information they track in romantic relationships, in the psychological mechanisms that process that information, and in the resultant behavior generated. Consistent with the discrete systems model, and in contrast to a competing "crossover" model, differences across relationships in feelings of love covaried with differences in strategic facilitation but not in strategic interference by partners. Similarly, differences in feelings of anger/upset during conflict covaried with differences in strategic interference but not strategic facilitation. In turn, feelings of love predicted commitment-promoting behavior but not partner-directed aggression, whereas levels of anger/upset predicted aggression but not commitment. As also predicted by our model, the love and anger/upset emotion systems converged to predict relationship satisfaction.

Adaptation, Psychological↗

Beyond screening for domestic violence: a systems model approach in a managed care setting.

BACKGROUND: Implementation of screening guidelines for domestic violence has been challenging. The multifaceted "systems model" may provide an effective means to improve domestic violence screening, identification, and intervention in the healthcare setting. METHODS: We developed: (1) a systems model approach using tools for effective referral, evaluation, and reporting of domestic violence; (2) materials for distribution to female patients; (3) training for social service and mental health clinicians to provide domestic violence evaluation; and (4) strong links to the community. SETTING: A nonprofit, managed care facility in Richmond, California. PARTICIPANTS: Staff and members of the managed care plan. MAIN OUTCOME MEASURES: (1) Increased screening for domestic violence by clinicians; (2) increased awareness of the healthcare facility as a resource for domestic violence assistance; and (3) increased member satisfaction with the health plan's efforts to address domestic violence. RESULTS: The number of clinician referrals and patient self-referrals to an on-site domestic violence evaluator increased more than twofold. A pre-intervention and post-intervention phone survey of members seen for routine checkup showed an increase in member recall of being asked about domestic violence. After intervention, statistically significant increases were seen in members' perception that the health plan was concerned about the health effects of domestic violence (p<0.0001) and about members' satisfaction with the health plan's efforts to address this issue (p<0.0001). CONCLUSIONS: A systems model approach improved domestic violence services in a managed care health setting within 1 year and affected clinicians' behavior as well as health plan members' experience. This successful implementation makes it possible to address critical research questions about the impact of a healthcare intervention for victims of domestic violence in a managed healthcare setting.

Adolescent↗

Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings.

Mixtures of amino acids, creatine, and glucose simulating the composition of six different kinds of meats (beef, chicken breast, chicken thigh, turkey breast, pork, and fish) were dry-heated to simulate the formation of heterocyclic amines in meats. The presence of 16 heterocyclic amines was investigated in the model systems and in the six meats and their corresponding meat drippings to determine the importance of meat composition to heterocyclic amine formation. Nine mutagenic amines (IQ, MeIQ, 8-MeIQx, 4,8-DiMeIQx, PhIP, IQx, IFP, DMIP, and TMIP) were found to be present at concentrations >0.1 ng/g in some of the model systems and in some of the meats or pan residues. Heterocyclic amine concentrations clearly are affected by precursor composition in this model system, and the same nine heterocyclic amines formed in the meat and in the model system show that this is a well-controlled surrogate for the reaction conditions that occur in meats during cooking.

Amines↗

Temperature measurements during phacoemulsification and erbium:YAG laser phacoablation in model systems.

PURPOSE: To compare the potential for thermal injury to ocular structure resulting from phacoemulsification ultrasound energy and erbium:YAG (Er:YAG) laser output. SETTING: Morse Laser Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. METHODS: Ultrasonic phacoemulsification energy and ER:YAG laser output (10 J/cm2, 10 Hz, 0.3 watts) sufficient for lens removal were applied to model systems and human cadaver eyes. Temperatures were measured with ultrafine thermocouples interfaced to a microcomputer data acquisition system. RESULTS: Although greater than 95% of energy from laser output is converted to thermal energy, temperature rise in model systems and cadaver eyes was 10 to 15 times greater after pulsed application of ultrasound energy than after Er:YAG laser application. At 100% power, approximately 4 watts of ultrasound power is converted to heat. Temperature rise following both laser and ultrasound applications decreased with irrigation in cadaver eyes and increasing volume in a model system. With continuous irrigation (20 cc/min), the temperature rise at 2 minutes measured at the corneal endothelial surface, within the corneal stroma, and in the anterior chamber angle of cadaver eyes was approximately 0.5 degrees Celsius (degrees C) after laser application and 7.0 degrees C after ultrasound application. Without irrigation, temperatures rose 2.5 degrees C after laser application and 35.0 degrees C after ultrasound application. CONCLUSION: At operating parameters sufficient for lens removal, the Er:YAG laser imparted less thermal energy to whole eyes and model systems than ultrasonic phacoemulsification.

Anterior Chamber↗

Computation of the passive electrical parameters of neurons using a system model.

Time-domain analysis of voltage responses to current pulse stimulation has been used to estimate the electrotonic parameters of neurons using the signal model. Errors are likely to accumulate from various steps of the analysis due to noise and electrode artifacts. A system model, which has inherent noise immunity and filtering properties, is presented here. This model employs frequency-domain analysis of the input impedance of a neuronal model (an RC cable). The resistances and capacitances of the system model are estimated from the cell-input impedance using an optimization strategy. Using the expression for the input impedance, any specified number of equalizing time constants can be computed exactly. The accessibility to these equalizing time constants 1) provides greater insight into the charge equalization along the length and circumference of the cable, and 2) improves the estimation of all other passive parameters including the electrotonic length. Thus, the system model approach allows information to be extracted more directly and accurately than the signal model approach.

Animals↗

Statistical considerations related to the use of caries model systems for the determination of clinical effectiveness of therapeutic agents.

Caries model systems bear great promise for the eventual determination of clinical benefits of therapeutic agents without the time and expense involved in the conduct of a full-fledged clinical trial. However, before such models can routinely be applied for such purposes, there are several issues which must first be resolved, including the consideration of a number of statistical matters. These include the assessment of the validity and reliability of the models to be so used. A procedure presented by Proskin, Chilton, and Kingman provides a quantitative means by which a conclusion concerning clinical effectiveness can be derived on the basis of data obtained through the use of a model system given that certain fairly general underlying conditions prevail. The present paper provides some discussion and recommendations of the author related to statistical matters concerning the use of models, and discusses the derivation and logic of the Proskin, Chilton, and Kingman procedure.

Cariostatic Agents↗

The ethylene/metal(0) and ethylene/metal(I) redox system: model ab initio calculations.

Ab initio calculations (coupled cluster with single and double excitations; CCSD) have been used to investigate the model redox systems ethylene:M(0) (M = Li, Na, K, Rb, Cs) and ethylene:M(I) (M = Be, Mg, Ca, Sr, Ba, Zn, Cd, Hg). Within C2v symmetry, the ground (2A1) states correspond to the charge distribution given in the title. The lowest (2B2) excited states correspond, somewhat counter intuitively, to the ethylene*-/=M(II)ion pair. These trends can be rationalized on the basis of simple electrostatic and configuration-mixing arguments that lead to two simple equations for predicting the electron-transfer energies for oxidation or reduction of the ethylene. The electron-transfer energies to the 2B2 ion pairs are dominated by the electrostatic ion-pairing energies.

Boron↗

Models and modeling systems in Alzheimer disease drug discovery.

The rapid pace of neurobiology research has increased the prospects of developing drugs to prevent neurodegenerative disorders. Although the goal of delaying the onset of brain disorders may be within the grasp of modern medicine, there are several critical barriers to progress. Among these is the lack of appropriate models and modeling systems for specific neurodegenerative diseases. Traditionally, in drug discovery, testing, and development, a combination of models is used. These include in vitro, in vivo, transgenic, and other animal models. However, each of these models has limitations. In this article, the author advocates the use of "in silico" modeling systems, which could complement currently available models and enable investigators to simulate alternative strategies to modulate neural function in a dynamic interactive mode. Advances in computer technology, including increasing speed and memory, and ready access to parallel processing systems have made it easier for investigators to develop databases for computer abstractions of neural function and dysfunction and to begin to develop prototypes for use in complex systems modeling environments. Multimodeling systems have been widely used in other areas of science to study emergent behavior of complex systems, such as the impact of atmospheric changes on weather, flight patterns of birds in a flock, and the behavior of traders in a commodities market. Adoption of such approaches should increase understanding of the complexities of signal transduction pathways in neural networks and accelerate the drug discovery process.

Alzheimer Disease↗

Dealkylation of N-nitrosodibenzylamine by metalloporphyrin/oxidant model systems for cytochrome P450.

N-Nitrosodialkylamines are alkylating carcinogens which are metabolically activated to alpha-hydroxy nitrosamines through oxidative dealkylation by cytochrome P450. In this study, the dealkylation step in the activation of N-nitrosodibenzylamine (NDBz) was investigated with metalloporphyrin/oxidant model systems under non-aqueous conditions, as biomimetic chemical models of cytochrome P450. In the model systems, NDBz was dealkylated and benzaldehyde was released. The catalytic activity required a porphyrin ring with a central metal that can interact with an oxidant. The oxidative activity of the model varied with the oxidant used in the order of tert-butyl hydroperoxide > cumene hydroperoxide > iodosobenzene, and also with the central metal of porphyrin used in the order of tetraphenylporphyrinatoiron(III) chloride > its manganese derivative. It was confirmed that N-nitrosodialkylamine undergoes oxidation to alpha-hydroxy nitrosamine in chemical model systems which are free of protein. These biomimetic models should be useful in elucidating the mechanisms of the metabolism of N-nitrosodialkylamines.

Benzaldehydes↗

Molecular recognition: comparative study of a tunable host-guest system by using a fluorescent model system and collision-induced dissociation mass spectrometry on dendrimers.

Host-guest interactions between the periphery of adamantylurea-functionalized dendrimers (host) and ureido acetic acid derivatives (guest) were shown to be specific, strong and spatially well-defined. The binding becomes stronger when using phosphonic or sulfonic acid derivatives. In the present work we have quantified the binding constants for the host-guest interactions between two different host motifs and six different guest molecules. The host molecules, which resemble the periphery of a poly(propylene imine) dendrimer, have been fitted with an anthracene-based fluorescent probe. The two host motifs differ in terms of the length of the spacer between a tertiary amine and two ureido functionalities. The guest molecules all contain an acidic moiety (either a carboxylic acid, a phosphonic acid, or a sulfonic acid) and three of them also contain an ureido moiety capable of forming multiple hydrogen bonds to the hosts. The binding constants for all 12 host-guest complexes have been determined by using fluorescence titrations by monitoring the increase in fluorescence of the host upon protonation by the addition of the guest. The binding constants could be tuned by changing the design of the acidic part of the guest. The formation of hydrogen bonds gives, in all cases, higher association constants, demonstrating that the host is more than a proton sensor. The host with the longer spacer (propyl) shows higher association constants than the host with the shorter spacer (ethyl). The gain in association constants are higher when the urea function is added to the guests for the host with the longer spacer, indicating a better fit. Collision-induced dissociation mass spectrometry (CID-MS) is used to study the stability of the six motifs using the corresponding third generation dendrimer. A similar trend is found when the six different guests are compared.

Journal Article↗

Xenopus egg extracts: a model system to study proprotein convertases.

The Xenopus egg extract translation system has proved an ideal tool with which to study the biosynthesis of the prohormone convertases. It provides a robust coupled translation/translocation system capable of efficient translocation of any protein containing an N-terminal signal sequence into the lumen of its microsomal membranes, with cotranslational cleavage of the signal peptide. Its main advantage over rival in vitro translation systems is that it will also carry out posttranslational modification of proteins, such as N-glycosylation, and, in the case of the proprotein convertases, support autocatalytic proregion removal. The egg extract also contains an endogenous, acidic pH optimum enzyme activity, suggestive of a proprotein convertase, that can undertake limited proteolysis of precursors containing multibasic processing sites.

Animals↗

Theories of family adaptability: toward a synthesis of Olson's Circumplex and the Beavers systems models.

Two typologies of family process, Olson's Circumplex Model and the Beavers Systems Model, are discussed, focusing particularly upon their definitions of family adaptability. It is argued that the two typologies are not simply "separate but equal" (11), but, rather, that there is an ambiguity in the Circumplex Model that disguises a fundamental theoretical overlap between the two. Olson's definition of adaptability is founded upon the concepts of morphogenesis and change; Beavers builds upon the concepts of negentropy and competence. It may be shown, however, that both understandings are necessitated by the theoretical writings of Olson and his colleagues. The nature of this ambiguity in the Circumplex Model is critically explored, and a higher-order model that attempts to synthesize these two theories is proposed.

Adaptation, Psychological↗

Phospholipid/cholesteryl ester microemulsions containing unesterified cholesterol: model systems for low density lipoproteins.

As models for the effects of unesterified cholesterol (UC) on the lipid organization of low density lipoprotein (LDL), microemulsions containing either egg yolk phosphatidylcholine (EYPC) or dimyristoyl phosphatidylcholine (DMPC) as the surface component, cholesteryl oleate (CO) as the core component, and varying amounts of unesterified cholesterol were prepared by sonication. Gel filtration chromatography showed coelution of each of the lipid components, demonstrating the formation of well-defined microemulsion populations. Unesterified cholesterol incorporation into the microemulsions was proportional to the composition of the original mixture at low unesterified cholesterol compositions, but reached saturation at compositions of approximately 15 and 10 mol% unesterified cholesterol for EYPC/CO and DMPC/CO microemulsions, respectively. The Stokes' radius of the microemulsions was constant and similar to native LDL for initial compositions less than 15 mol% unesterified cholesterol, but increased at compositions above 15 mol%. In both EYPC/CO/UC and DMPC/CO/UC microemulsions, no significant changes were observed for the calorimetric or Van't Hoff enthalpy for the thermal transition of the core cholesteryl ester; however, increases in the transition temperature as a function of increasing unesterified cholesterol composition suggests that unesterified cholesterol has a stabilizing effect on the core transition. In DMPC/CO/UC microemulsions, the effect of unesterified cholesterol on the surface-located DMPC could be clearly observed as a broadening of the thermal transition of the acyl chains. These results demonstrate that unesterified cholesterol is located primarily in the surface of these protein-free lipid model systems for LDL.

Biophysical Phenomena↗