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Results for “Model explainability”

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At least 379 records · Page 21Linked to original sources

PubMed2006

Self-assembly of (perfluoroalkyl)alkanes on a substrate surface from solutions in supercritical carbon dioxide.

Toroidal self-assembled structures of perfluorododecylnonadecane and perfluorotetradecyloctadecane have been deposited on mica and highly oriented pyrolytic graphite surfaces by exposure of the substrates to solutions of the (pefluoroalkyl)alkanes in supercritical carbon dioxide. Scanning force microscopy (SFM) images have displayed a high degree of regularity of these self-assembled nanoobjects regarding size, shape, and packing in a monolayer. Analysis of SFM images allowed us to estimate that each toroidal domain has an outer diameter of about 50 nm and consists of several thousands of molecules. We propose a simple model explaining the clustering of the molecules to objects with a finite size. The model based on the close-packing principles predicts formation of toroids, whose size is determined by the molecular geometry. Here, we consider the amphiphilic nature of the (perfluoroalkyl)alkane molecules in combination with incommensurable packing parameters of the alkyl- and the perfluoralkyl-segments to be a key factor for such a self-assembly.

Alkanes↗

PubMed2001

Social psychological models of choice behavior and drivers' left turns.

ABSTRACT. The authors reanalyzed data from a simulated left-turn experiment (P. A. Hancock, J. K. Caird, S. Shekhar, & M. Vercruyssen, 1991) to test the adequacy of the nonlinear Gray-Tallman satisfaction balance model of choice behavior (L. N. Gray & I. Tallman, 1984) in predicting left turns. Participants (Hancock et al., 1991) were 40 experienced U.S. drivers who were exposed to simulated oncoming traffic; the size of the vehicle (motorcycle, compact vehicle, full-sized vehicle, delivery truck), its speed (10-70 mph, or 16-112 kmph), and the intervehicle time gap (3-9 s) varied. Hancock et al. (1991) measured (a) the likelihood of a left turn and (b) the occurrence of a collision. The probability of a left turn was greater for larger intervehicle time gaps and for oncoming smaller vehicles traveling at higher speeds. The Gray-Tallman (1984) model explained 69% of the variation in turning versus 57% for a linear regression model. In making decisions people tend to treat the values and costs affecting choices in a multiplicative, rather than linear, fashion. The Gray-Tallman model also has the potential for incorporating, both theoretically and mathematically, an unlimited range of potential values and costs that may influence left turn decisions.

Adult↗

PubMed1999

A two-phase charge-density real-space-pairing model of high-Tc superconductivity.

It is usually assumed that high-T(c) superconductors have a periodic band structure and a periodic charge density, although amorphous low-T(c) superconductors are known. In this paper, it is suggested that the CuO(2) conduction planes of cuprate superconductors consist of regions of two different charge densities which do not normally repeat periodically. It is suggested that the pairing of holes occurs in real space in cuprate superconductors. It is proposed that the hole-pairing mechanism is magnetic exchange coupling and the pairing force is strong, the pairing energy being greater than kT at room temperature. The bound hole pair is essentially a bipolaron. A real-space model is very tentatively suggested in which the CuO(2) planes of YBa(2)Cu(3)O(7) contain nanodomains of a 3 x 3 hole lattice surrounded by interfaces one unit cell wide in which the holes are paired. In the superconducting state in this model, the existing hole pairs condense and move coherently and collectively around the insulating nanodomains, like trams running around blocks of houses, with one hole on each tramline. The hole pairs move in an elegant manner with hole pairs hopping from oxygen to oxygen via adjacent copper sites. The model explains the superconducting current being in the ab plane and it also explains the very short coherence lengths. Because the pairing force is strong, the model suggests that room-temperature superconductivity might be possible in carefully designed new oxide materials.

Journal Article↗

PubMed2026

Evaluation of population-specific polygenic risk scores for blood lipids: insights from Taiwanese cohorts and multiancestry meta-analysis.

BACKGROUND: Blood lipids are heritable risk factors for cardiovascular disease (CVD), a leading cause of mortality worldwide. However, the genetic architecture of lipid traits and the performance of polygenic risk scores (PRSs) remain underexplored in East Asian (EAS) populations, including Taiwanese Han individuals. METHODS: We conducted genome-wide association studies and PRS analyses for five lipid traits: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the ratio of low-density lipoprotein cholesterol to total cholesterol. Lipid profile data were obtained from the China Medical University Hospital cohort. PRSs were evaluated on the basis of their correlations with measured lipid levels. To evaluate trans-ancestry PRS transferability, localized models were systematically compared against models derived from discovery-stage GWAS meta-analyses incorporating five ancestry groups from the Global Lipids Genetics Consortium. The performance of the PRS models in predicting lipid-related diseases was evaluated through receiver operating characteristic curve analyses. RESULTS: The population-specific PRS models explained 11%-40% of the variance in lipid levels within the target cohort. Models leveraging global multiancestry GWAS meta-analysis weights revealed limited predictive performance (r 2 = 0.04-0.19), whereas analyses incorporating EAS-specific data yielded higher correlations (r 2 = 0.13-0.30), although these correlations did not exceed those derived from the hospital-based cohort alone. When combined with age and sex, the PRS models demonstrated strong predictive performance for coronary artery disease, atherosclerosis, and ischemic stroke, with area under the curve values of 0.910, 0.926, and 0.854, respectively. CONCLUSION: Population-specific PRS models derived from a Taiwanese population outperformed meta-analysis-derived frameworks in predicting lipid levels and demonstrated substantial potential for predicting CVD risk, indicating the importance of ancestry-matched genetic studies in precision medicine.

LDL-C/TC ratio↗

PubMed2000

A molecular model of agonist and nonpeptide antagonist binding to the human V(1) vascular vasopressin receptor.

The affinity of the nonpeptide antagonist OPC-21268 is greater for the rat V(1) arginine vasopressin (AVP) receptor (V(1)R) than for the human V(1)R. Site-specific mutagenesis was carried out to identify the residues that determine interspecies selectivity for nonpeptide antagonist binding. The introduction of rat amino acids in position 224, 310, 324, or 337 of the human V(1)R sequence dramatically altered OPC-21268 affinity for the receptor, whereas binding of AVP, the peptide V(1)R antagonist d(CH(2))(5)Tyr(Me)AVP, and the nonpeptide V(1)R antagonist SR49059 was not altered by these mutations. Computer modeling explained the mutagenesis results. Docking of OPC-21268 onto a homology-built model of the V(1)R receptor yielded a model for the bound ligand in which the hydrophobic part is deeply embedded in the transmembrane region, whereas the polar part is located on the surface of the extracellular side. The increased affinity of the G337A mutant is due to two additional van der Waals contacts of the alanine methyl group with carbon atoms on the antagonist. The I310V mutant reduces the hydrophobicity in the vicinity of the polar oxygen atom of the antagonist. The I224V mutant relieves overcrowding in a hydrophobic binding pocket involving the aromatic residues Trp(175), Phe(179), Phe(307), and Trp(304). Finally, the E324D mutant enables the formation of a hydrogen bond of the carboxylate side chain with the amide side chain of Gln(311), which in turn forms a hydrogen bond with the N57 nitrogen atom of OPC-21268. Thus, a few residues, distinct from those involved in agonist binding, control interspecies selectivity toward OPC-21268 nonpeptide antagonist binding.

Amino Acid Sequence↗

PubMed1994

Pharmacokinetics of apomorphine in Parkinson's disease: plasma and cerebrospinal fluid levels in relation to motor responses.

In this study, we measured the relationship between plasma and cerebrospinal fluid (CSF) apomorphine levels and their clinical effects in two patients with Parkinson's disease (PD). After subcutaneous injection of apomorphine, serial samples of plasma and lumbal CSF were taken and serial scoring of motor responses was done using the Webster Rating Scale. The ratio of the highest level of apomorphine in CSF and plasma was 0.036 for patient A and 0.025 for patient B. The time lag between the highest level of apomorphine in plasma and CSF was 20 min for patient A and 10 min for patient B. Plasma levels of apomorphine correlated weakly with clinical motor responses. However, we could establish a highly strong correlation between apomorphine CSF levels and clinical motor responses: 0.93 and 0.89 for patients A and B, respectively. We conclude that a two-compartment pharmacokinetic model explains the clinical effects of apomorphine better than does a one-compartment model. In a two-compartment model, clinical effect can clearly be correlated to apomorphine levels in the central compartment.

Apomorphine↗

PubMed1996

[Adaptation to the community by young adults after one or more psychiatric hospitalizations].

This longitudinal study aimed at elaborating a model explaining the adaptation to the community of young adults suffering from mental illness. During their sick leave, an interview evaluated their social support, the stress experienced, coping strategies and emotional distress. Six months later, therapists were interrogated as to the recourse of these young adults to psychiatric services, their loyalty to therapeutic and medical treatment as well as how they kept busy during that period. Analyses by structural equations (LISREL) have allowed to develop a model which adequately reproduces relations observed between variables and explains 43% of the total variance. This model also indicates that the level of psychological distress has a direct impact on a psychiatric rehospitalization.

Adolescent↗

PubMed2002

Exploring predictors of eating behaviour among adolescents by gender and socio-economic status.

OBJECTIVE: Guided by theory, this study explored cross-sectional differences in factors influencing adolescent eating behaviour including gender and socio-economic status (SES), and subsequently tested the longitudinal predictive power of the models. DESIGN/SETTING/SUBJECTS: Data were collected by questionnaires in a longitudinal study of adolescents (age 13 years at baseline) and their parents from Hordaland County, Norway. Association of personal and environmental variables (family, friends, school/society) with the consumption of fruit and vegetables (FV) and selected sources of fat and of sugar were assessed at age 15 The final cross-sectional models were subsequently employed in groups stratified by gender/SES and to predict consumption at age 21 RESULTS: The model explained more of the variation in the sugar score (21%) and the FV score (13.5%) than in the fat score (5%). SES was associated with both the sugar and FV scores. The strongest associations with the sugar score and FV were for antisocial behaviour and evaluation of own diet, respectively. The former association was significant in all gender/SES groups, whereas the latter association was only significant in the low SES groups. For all three types of food, the strongest significant predictors in the longitudinal models were frequency of consumption at age 15. CONCLUSION: The model's ability to explain variation in eating behaviours differed by food type, and possibly by gender/SES, but previous eating behaviour was an important predictor for all three foods. Prospective studies should carefully operationalize theoretical constructs when further investigating the influences of and interrelationships between these factors and gender/SES on the development of eating behaviours.

Adolescent↗

PubMed2003

Zwicker tone illusion and noise reduction in the auditory system.

The Zwicker tone is an auditory aftereffect. For instance, after switching off a broadband noise with a spectral gap, one perceives it as a lingering pure tone with the pitch in the gap. It is a unique illusion in that it cannot be explained by known properties of the auditory periphery alone. Here we introduce a neuronal model explaining the Zwicker tone. We show that a neuronal noise-reduction mechanism in conjunction with dominantly unilateral inhibition explains the effect. A pure tone's "hole burning" in noisy surroundings is given as an illustration.

Auditory Pathways↗

PubMedDate not supplied

Understanding the interactions between physician assistants and their supervising physicians in the provision of patient care.

A great deal of discussion and debate has surrounded the issue of autonomy of practice among physician assistants (PAs) and other non-physician clinicians. This study further explores this issue by closely examining the interactions between PAs and their supervising physicians in the provision of patient care. Utilizing a national sample of 1,112 full-time practicing physician assistants, PA-MD interaction patterns are measured and weighted in a scale as a proxy for autonomy of practice. Further, these measures are then used as the dependent variable in a regression analysis to better explain the dynamics between PA personal and practice characteristics and autonomy of practice. Overall, the tested model explained 29% of the variation in PA-MD interaction patterns. Independent variables that were particularly influential in the model were proximity to supervisor, clinical productivity, the percentage of PA patients treated using written clinical guidelines, specialty of practice, and practice setting.

Humans↗

PubMed2004

Addiction, a condition of compulsive behaviour? Neuroimaging and neuropsychological evidence of inhibitory dysregulation.

AIMS: Addiction has been conceptualized as a shift from controlled experimentation to uncontrolled, compulsive patterns of use. Current neurobiological models of addiction emphasize changes within the brain's reward system, such that drugs of abuse 'hijack' this system and bias behaviour towards further drug use. While this model explains the involuntary nature of craving and the motivational drive to continue drug use, it does not explain fully why some addicted individuals are unable to control their drug use when faced with potentially disastrous consequences. In this review, we argue that such maladaptive and uncontrolled behaviour is underpinned by a failure of the brain's inhibitory control mechanisms. DESIGN: Relevant neuroimaging, neuropsychological and clinical studies are reviewed, along with data from our own research. FINDINGS: The current literature suggests that in addition to the brain's reward system, two frontal cortical regions (anterior cingulate and orbitofrontal cortices), critical in inhibitory control over reward-related behaviour, are dysfunctional in addicted individuals. These same regions have been implicated in other compulsive conditions characterized by deficits in inhibitory control over maladaptive behaviours, such as obsessive-compulsive disorder. CONCLUSIONS: We propose that in chronically addicted individuals, maladaptive behaviours and high relapse rates may be better conceptualized as being 'compulsive' in nature as a result of dysfunction within inhibitory brain circuitry, particularly during symptomatic states. This model may help to explain why some addicts lose control over their drug use, and engage in repetitive self-destructive patterns of drug-seeking and drug-taking that takes place at the expense of other important activities. This model may also have clinical utility, as it allows for the adoption of treatments effective in other disorders of inhibitory dysregulation.

Behavior, Addictive↗

PubMed1998

Plasma sex hormones are significantly associated with plasma leptin concentration in healthy subjects.

OBJECTIVE: In humans a sexual dimorphism of plasma leptin concentration has been demonstrated but its significance remains to be established. Sex hormones may have a role. PATIENTS: Eighty healthy, non-obese subjects (41M/39F) were studied. MEASUREMENTS: In the whole group of subjects plasma sex hormones, leptin and insulin concentrations were determined, body fat content assessed by bioimpedance analysis, body fat distribution evaluated and insulin-mediated glucose uptake measured by euglycemic hyperinsulinemic glucose. RESULTS: After adjustment for age, gender, amount of body fat, waist/hip ratio (WHR) and fasting plasma insulin concentration, fasting plasma leptin was still significantly correlated with plasma DHEAS (r = -0.30, P < 0.006), oestradiol (r = 0.53, P < 0.001) and testosterone (r = -0.43, P < 0.001) in all subjects (n = 80). Independently of age, amount of body fat and WHR, fasting plasma leptin concentration correlated with plasma oestradiol (r = 0.38, P < 0.01) and total testosterone (r = -0.58, P < 0.001) in males (n = 41) and with fasting plasma oestradiol (r = 0.48, P < 0.002) in females (n = 39). To investigate the independent contribution of anthropometric and hormonal variables to fasting plasma leptin concentration, a multivariate stepwise regression analysis with fasting plasma leptin concentration as dependent variable was made. In the entire group (n = 80), the whole model explained 43% of fasting plasma leptin concentration with fasting plasma insulin, total testosterone and oestradiol concentrations significantly and independently associated with plasma leptin concentration. In this model, fasting plasma DHEAS, testosterone and oestradiol explained 25% of the variability in plasma leptin concentration. CONCLUSION: Our study demonstrates that plasma sex hormone concentrations are associated with plasma leptin concentration.

Analysis of Variance↗

PubMed1987

Molecular mechanics calculations of dA12.dT12 and of the curved molecule d(GCTCGAAAAA)4.d(TTTTTCGAGC)4.

Using the AMBER software package (Weiner and Kollman 1981) substantially modified for electrostatic contributions, the structural energies of the double-stranded oligonucleotides dA12.dT12 and d(GCTCGAAAAA)4.d(TTTTTCGAGC)4 were minimized. Using various starting structures for the molecule dA12.dT12, one final structure is obtained which possesses the experimentally determined properties of poly(dA).poly(dT). This structure is an A-form-B-form-hybrid structure similar to that of Arnott et al. (1983). The dA-strand is similar to an A-form while the dT-strand is similar to normal B-form. This structure and separately optimized B-form sequence stretches were used to construct the double-stranded fragment d(GCTCGAAAAA)4 which again was optimized. This sequence, when imbedded in a DNA fragment as contiguous repeats, shows a gel migration anomaly which has been interpreted as stable curvature of the DNA (Diekmann 1986). The calculated structure of this sequence indeed has a curved helix axis and is discussed as a model for curved DNA. A theoretical formalism is presented which allows one to calculate the structural parameters of any nucleic acid double helix in two different geometrical representations. This formalism is used to determine the parameters of the base-pair orientations of the curved structure in terms of wedge as well as cylindrical parameters. In the structural model presented here, the curvature of the helix axis results from an alternation of two different DNA structures in which the base-pairs possess different angles with the helix axis ('cylinder tilt'). Resulting from geometric restraints, a negative cylinder tilt angle correlates strongly with the closing of the minor groove ('wedge roll'). The blocks with different structure are not exactly coincident with the dA5-blocks and the B-DNA stretches. Within the dA5 block, base-pair tilt and wedge roll adopt large values which proceed into the 3' flanking B-DNA sequence by about one base-pair. These properties of the structure calculated here are discussed in terms of different models explaining DNA curvature.

DNA↗

PubMed2006

QTL associated with horizontal resistance to soybean cyst nematode in Glycine soja PI464925B.

Soybean cyst nematode (Heterodera glycines Ichinohe; SCN) is the primary disease responsible for yield loss of soybean [Glycine max (L.) Merr.]. Resistant cultivars are an effective management tool; however, the sources currently available have common resistant genes. Glycine soja Sieb. and Zucc., the wild ancestor of domesticated soybean, represents a diverse germplasm pool with known SCN resistance. The objectives of this research were to: (1) determine the genetic variation and inheritance of SCN resistance in a G. max ('S08-80') x G. soja (PI464925B) F (4:5) recombinant inbred line (RIL) population; and (2) identify and evaluate quantitative trait loci (QTL) associated with SCN resistance. Transgressive segregation for resistance was observed, although neither parent was resistant to the Chatham and Ruthven SCN isolates. Broad sense heritability was 0.81 for the Ruthven and 0.91 for the Chatham isolate. Root dry weight was a significant covariate that influenced cyst counts. One RIL [female index (FI) = 5.2 +/- 1.11] was identified as resistant to the Chatham isolate (FI < 10). Seventeen and three RILs infected with Chatham and Ruthven isolates, respectively, had mean adjusted cyst counts of zero. Unique and novel QTL, which derived resistance from G. soja, were identified on linkage groups I, K, and O, and individually explained 8, 7 and 5% (LOD = 2.1-2.7) of the total phenotypic variation, respectively. Significant epistatic interactions were found between pairs of SSR markers that individually may or may not have been associated with SCN resistance, which explained between 10 and 15% of the total phenotypic variation. Best-fit regression models explained 21 and 31% of the total phenotypic variation in the RIL population to the Chatham and Ruthven isolates, respectively. The results of this study help to improve the understanding of the genetic control of SCN resistance in soybean caused by minor genes resulting in horizontal resistance. The incorporation of the novel resistance QTL from G. soja could increase the durability of SCN-resistance in soybean cultivars, especially if major gene resistance breaks down.

Animals↗

PubMed1998

Fiber-based anterior cruciate ligament model for biomechanical simulations.

Although accurate predictions of the behavior and function of the anterior cruciate ligament would aid in diagnosis and operative treatment, no agreement exists on the best way to model the ligament with a reliable description of its mechanical and geometric features. We propose a new model of the anterior cruciate ligament based on multiple viscoelastic curvilinear fibers. This model was used for quasi-static simulations of the passive motion of eight porcine knees, after registration of the passive trajectories and digitization of the surface of the ligament in flexion. Simulations of anterior cruciate ligament deformations during passive motion predicted a fiber strain of less than 20%, low insertion forces, and isometric anterior fibers. The model explains actions of the ligament fibers, as reported in the literature, better than classic models based on linear fibers and consistent with the mechanical properties of the anterior cruciate ligament.

Animals↗

PubMed1993

Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells.

BACKGROUND: Liver dysfunction is a common manifestation of cystic fibrosis (CF), a disease caused by mutations affecting the CF transmembrane conductance regulator (CFTR). The aim of this study was to examine the distribution and role of CFTR in liver. METHODS: CFTR messenger RNA was detected in cryosections of human liver by in situ hybridization. CFTR immunoreactivity was detected using antibodies raised against two CFTR peptides. RESULTS: The predominant site of CFTR messenger RNA and immunoreactivity in liver is the intrahepatic bile duct. CFTR is not detected in hepatocytes of normal liver or in livers exhibiting bile duct proliferation. Within bile duct cells, CFTR is localized at or near the apical plasma membrane. CONCLUSIONS: The apical localization of CFTR in bile duct cells suggests a model explaining how the CFTR-associated Cl- channel contributes to normal biliary secretion. This model suggests that if CFTR expression could be promoted in intrahepatic duct cells by somatic gene therapy, this might prevent the occurrence of liver disease in CF.

Antiporters↗

PubMed2002

Meaningless minis? Mechanisms of neurotransmitter-receptor clustering.

Initiation and maintenance of the postsynaptic neurotransmitter-receptor field are important steps during synapse formation and maturation, as they play a determinative role in regulating synaptic strength. However, the mechanisms directing neurotransmitter-receptor clustering and maintenance are poorly understood. Recently, two models explaining glutamate-receptor clustering at the Drosophila neuromuscular junction have been proposed. One model postulates that release of an agent via single vesicle fusion events (minis) is required for the initiation of postsynaptic glutamate-receptor clustering, and that glutamate is not responsible for initiation or maintenance of the postsynaptic receptor field. The other model rules out a role for minis in initiation of clustering, and suggests a role for non-vesicular release of glutamate in receptor-field maintenance. Here, we compare and discuss the data underlying both models.

Animals↗

PubMed1999

Molecular modeling of human P450c17 (17alpha-hydroxylase/17,20-lyase): insights into reaction mechanisms and effects of mutations.

P450c17 (17alpha-hydroxylase/17,20-lyase) catalyzes steroid 17alpha-hydroxylase and 17,20-lyase activities in the biosynthesis of androgens and estrogens. These two activities are differentially regulated in a tissue-specific and developmentally programmed manner. To visualize the active site topology of human P450c17 and to study the structural basis of its substrate specificity and catalytic selectivity, we constructed a second-generation computer-graphic model of human P450c17. The energetics of the model are comparable to those of the principal template of the model, P450BMP, as determined from its crystallographic coordinates. The protein structure analysis programs PROCHECK, WHATIF, and SurVol indicate that the predicted P450c17 structure is reasonable. The hydrophobic active site accommodates both delta4 and delta5 steroid substrates in a catalytically favorable orientation. The predicted contributions of positively charged residues to the redox-partner binding site were confirmed by site-directed mutagenesis. Molecular dynamic simulations with pregnenolone, 17-OH-pregnenolone, progesterone, and 17-OH-progesterone docked into the substrate-binding pocket demonstrated that regioselectivity of the hydroxylation reactions is determined both by proximity of hydrogens to the iron-oxo complex and by the stability of the carbon radicals generated after hydrogen abstraction. The model explains the activities of all known naturally occurring and synthetic human P450c17 mutants. The model predicted that mutation of lysine 89 would disrupt 17,20-lyase activity to a greater extent than 17alpha-hydroxylase activity; expression of a test mutant, K89N, in yeast confirmed this prediction. Hydrogen peroxide did not support catalysis of the 17,20-lyase reaction, as would be predicted by mechanisms involving a ferryl peroxide. Our present model and biochemical data suggest that both the hydroxylase and lyase activities proceed from a common steroid-binding geometry by an iron oxene mechanism. This model will facilitate studies of sex steroid synthesis and its disorders and the design of specific inhibitors useful in chemotherapy of sex steroid-dependent cancers.

Amino Acid Sequence↗