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PubMed2002

Molecular modeling of eluted peptides from DQ6 molecules (DQB10602 and DQB10604) negatively and positively associated with type 1 diabetes.

Insulin-dependent diabetes mellitus (IDDM) is positively associated with HLA-DQ8, DQ2, and DQ6 (B*0604) and negatively with DQ6 (B*0602). The mechanisms by which the DQ molecules control the development of IDDM is not known. DQ6 (B*0602) and DQ6 (B*0604) molecules share the same DQalpha chain but differ in the beta chain by six residues at positions 9, 30, 57, 70, 86, and 87. The aim of the study was to sequence the peptides eluted from both DQ6 molecules and to determine the binding motifs and construct peptides for docking them into the DQ6 peptide binding groove by molecular modeling. EBV transformed B cell line homozygous for DQ6 and hybridoma cell line secreting DQ6 specific antibody were grown in large-scale culture. The DQ6 molecules were precipitated with solid-phase bound antibodies specific for DQ6. The dissociation of peptides from MHC was done with ultrafiltration and separation of peptides by reversed-phase HPLC, using Edman degradation. A special application of Edman degradation is pool sequencing. This approach allowed us to determine common characteristics of all peptides associated with a given MHC molecule. The precipitation of DQ6 molecules and the peptide elution were done successfully. The sequencing of the peptides from DQ6 (B*0602) identified three fractions: (1) IINEPTAAAIAYGLD (Bovine HSP70), (2) IINEPTAAAIAGLDR (Human HSP70), and (3) NPRDAKACVVHGSDLK (Na+/K+ ATPase). Peptide eluted from DQ6 (B*0604) had a sequence ADLFRGTLDPVEK with sequence homology to HSP70 (residues 307-319). We were able to predict the motifs for DQ6 from the ligands eluted. We used molecular modeling as a tool to identify plausible binding motifs for peptides. Our studies show that peptide ADLFRGTLDPVEK and NPRDAKACVVHGSDLK fit well in the respective DQ6 binding grooves. These predicted motifs should then be useful for screening of autoantigens associated with diabetes and identifying the epitopes that are likely to interact with T cells.

Amino Acid Sequence↗

PubMed2001

Effects of phorbol ester and dexamethasone treatment on histidine decarboxylase and ornithine decarboxylase in basophilic cells.

Both histamine and polyamines are important for maintaining basophilic cell function and viability. The synthesis of these biogenic amines is regulated by histidine decarboxylase and ornithine decarboxylase, respectively. In other mammalian tissues, an interplay between histamine and polyamine metabolisms has been suspected. In this report, the interplay between histamine and ornithine-derived polyamines was studied in a non-transformed mouse mast cell line (C57.1) treated with phorbol ester and dexamethasone, a treatment previously used to increase histidine decarboxylase expression in mastocytoma and basophilic leukemia. Treatment with phorbol ester and dexamethasone increased histidine decarboxylase expression and intracellular histamine levels in C57.1 mast cells to a greater extent than those found for other transformed basophilic models. The treatment also induced a reduction in ornithine decarboxylase expression, intracellular polyamine contents, and cell proliferation. These results indicate that the treatment induces a co-ordinate response of polyamine metabolism and proliferation in mast cells and other immune-related cells. The decrease in the proliferative capacity of mast cells caused by phorbol ester and dexamethasone was simultaneous to an increase in histamine production. Our results, together with those reported by other groups working with polyamine-treated mast cells, indicate an antagonism between histamine and polyamines in basophilic cells.

Animals↗

PubMed1999

BSAP/Pax5A expression blocks survival and expansion of early myeloid cells implicating its involvement in maintaining commitment to the B-lymphocyte lineage.

Early B lymphopoiesis is marked by plasticity between the myeloid and B lineages. An attractive model for B-lineage development is that commitment to this lineage is partly determined by the ordered expression of genes that prohibit switching to the myeloid lineage. In this regard, whereas the role of the B-cell-specific transcription factor BSAP/Pax5A in regulating B-lymphoid-restricted gene expression has been well-established, its role in maintaining B-lineage commitment is unclear. Thus, BSAP/Pax5A was constitutively expressed in the multipotent EML cell line, which can be directed toward the myeloid lineage by culture with interleukin-3 (IL-3) and retinoic acid. EML cells expressing BSAP/Pax5A successfully acquired the myeloid lineage markers CD11b and F4/80 in response to IL-3 and retinoic acid, indicating differentiation to the myeloid lineage. However, these early myeloid cells failed to expand in culture with granulocyte-macrophage colony-stimulating factor and were directed instead toward an apoptotic pathway. In parallel, primary bone marrow stem cells transduced with retrovirus constitutively expressing BSAP/Pax5A began myeloid cell differentiation, but like the transformed EML model failed to expand in response to myeloid growth factors. These studies identify a role for BSAP/Pax5A in suppressing the response to myeloid growth factors, which may be a component of the regulatory processes that limit plasticity of early B-lymphoid progenitors.

B-Lymphocytes↗

PubMedDate not supplied

Apollo 11: an experiential model for team-based transformational change.

Transformational change, or reengineering, is a tough assignment for any organization. The pay-off, however, can be huge: happier patients, reenergized staff, and increased productivity. This article describes the team-based Apollo 11 project at Southeast Health Center in Indianapolis. Although this redesign effort took 7 months of extraordinary team effort, it resulted in a 54% reduction in patient encounter time, a decrease of more than 40% in per-visit cost, and improved patient and staff satisfaction. This article summarizes the background and dynamics of Apollo 11, shares some initial project results, and summarizes the lessons learned, so that other healthcare organizations can successfully tackle the reengineering challenge.

Community Health Centers↗

PubMed2006

A decision aid for GPs for the treatment of elderly male patients with lower urinary tract symptoms (LUTS).

BACKGROUND: GPs have four main treatment options for lower urinary tract symptoms (LUTS): watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors or (referral for) surgery. Guidelines do not provide clear cut-off values for (combinations of) symptoms and physical examination results to decide which treatment is best. OBJECTIVE: (i) To develop a decision aid ('checklist') for GPs for the treatment of patients with LUTS. (ii) To assess its value for use in a primary care population. Materials and methods. Population-based cross-sectional study. Included were subjects with uncomplicated LUTS for whom treatment in primary care may be appropriate. [International Prostate Symptom Score (IPSS) > or = 8, no prior prostate surgery, prostate-specific antigen (PSA) value < 10 ng/ml]. For each subject the appropriateness of surgery and alpha-blocker treatment was determined using a previously validated formalized international expert panel judgement. Regression models using data available in primary care were constructed to predict the panel judgement. Subsequently these models were transformed into simple checklists. Finally, the efficiency of these checklists was calculated. RESULTS: The best checklists consisted of age, symptoms severity, type of symptoms, a quality of life score and PSA value. Assuming one would like to provide at least 95% of the subjects for whom a certain treatment is appropriate with this treatment (i.e. 'sensitivity' of the checklist > or = 95%), one can reach a positive predictive value of 50-60%. CONCLUSION: Simple checklists based on the judgement of experts regarding the most appropriate therapy can help GPs to advise their patients of a rational treatment strategy.

Adrenergic alpha-Antagonists↗

PubMed2006

[A study of coordinates transform iterative fitting method to extract bio-impedance model parameters bio-impedance model parameters].

A new algorithm, the coordinates transform iterative optimizing method based on the least square curve fitting model, is presented. This arithmetic is used for extracting the bio-impedance model parameters. It is superior to other methods, for example, its speed of the convergence is quicker, and its calculating precision is higher. The objective to extract the model parameters, such as Ri, Re, Cm and alpha, has been realized rapidly and accurately. With the aim at lowering the power consumption, decreasing the price and improving the price-to-performance ratio, a practical bio-impedance measure system with double CPUs has been built. It can be drawn from the preliminary results that the intracellular resistance Ri increased largely with an increase in working load during sitting, which reflects the ischemic change of lower limbs.

Algorithms↗

PubMed2005

Stone formation is proportional to papillary surface coverage by Randall's plaque.

PURPOSE: Randall's plaques are common in calcium oxalate (CaOx) stone formers (SF). Plaque coverage correlates directly with urine calcium excretion and inversely with urine volume. We hypothesize that plaque coverage should increase proportionally with increasing stone number. We measured plaque areas in idiopathic CaOx stone formers and nonstone formers (NSF), and identified significant relationships with quantified stone histories. MATERIALS AND METHODS: A total of 13 SFs and 4 control NSFs underwent nephroscopic papillary mapping with representative still images and MPEG (Moving Pictures Experts Group) movies used to identify plaque and papillary borders. Stone histories were obtained through patient interviews, and from medical records and radiographs. The relationship of plaque coverage to clinical stone events was assessed by general multivariate linear modeling. Log transformation normalized the distribution of percent plaque coverage and stone number. RESULTS: Plaque surface area in SFs differed significantly from that in NSFs (p <0.0001). The duration of stone disease and the log transformed percent plaque coverage correlated significantly with the number of stones (0.677 and 0.620, p = 0.003 and 0.008, respectively). On multivariate analysis and correcting for the duration of stone disease total percent plaque coverage correlated significantly with the number of stones (R = 0.496, p = 0.05). Disease duration and plaque coverage did not correlate significantly (p = 0.257). CONCLUSIONS: Percent plaque coverage directly correlates with the number of stones formed even when corrected for the duration of stone disease. However, plaque coverage does not correlate with the duration of stone disease. These results support the hypothesis that the pathogenesis of CaOx stones begins with Randall's plaques.

Biopsy↗

PubMed1998

The potential role of transforming growth factor beta in fracture healing.

As shown in previous studies, the transforming growth factor beta superfamily of growth factors is involved in many aspects of skeletal development and regulation, including fracture repair and bone regeneration. Several studies have shown transforming growth factor beta messenger ribonucleicacid and protein expression in cells comprising fracture callus. In healing fractures in a chick model, differential isoform expression of the transforming growth factor betas was observed by in situ hybridization, with more prominent expression of the transforming growth factor beta 2 and transforming growth factor beta 3 isoforms. Small amounts of transforming growth factor beta 1 were present in early callus and increased in expression later during chondrogenesis and endochondral ossification. These findings resemble those reported in rat and human fracture callus. Transforming growth factor beta 4 expression was not significant in the chick fracture model. Transforming growth factor beta can function as a morphogen when injected subperiosteally, inducing cartilage and bone formation that morphologically resembles many of the events occurring in fracture callus. Exogenous transforming growth factor beta has been used in several critical size defect models of bone regeneration and fracture healing, with most of the studies showing increased bone or callus formation and increased mechanical stability. Numerous variables, including markedly different dose ranges and differing isoforms, dosing regimens, delivery methods, animal models, and various times and endpoint measures for analysis, make it difficult to comparatively assess the effects of transforming growth factor beta on bone healing. Additional study is necessary to satisfactorily determine the role of transforming growth factor beta in normal fracture healing and its potential for use in augmenting this process.

Animals↗

PubMed1987

Simultaneous genetic evaluation of sires and cows for a large population of dairy cattle.

A strategy for simultaneous sire and cow evaluation of genetic merit was implemented. First lactation records of 1,074,971 Holstein cows in 20,065 herds were included. After inclusion of ancestors, there were 1,741,356 equations: 1,505,938 cow, 229,394 herd-year-season, 6000 sire, and 24 genetic group equations. All known genetic relationships among animals were considered. Genetic group coefficients were assigned based on animals that had one or more parents unidentified. Mixed model equations from an animal model were transformed to solve for total additive genetic merit. The coefficient matrix was sparse with .00039% nonzero elements. Equations were blocked by herds. A final block included sires, groups, and cows that had no daughters or records. Effects of herd-year-season were solved last within each herd. All herd blocks were solved before sire equations. A form of block iteration with successive overrelaxation was used to obtain solutions. A total of 30 rounds were completed. Number of iterations per round for herd blocks decreased from an average of 4.93 in round 1 to the minimum allowed, 3.00, in round 30. The correlation between Northeast Artificial Insemination Sire Comparisons and sire solutions from this study stabilized at .94. At round 30, 96.4, 95.2, 99.4, and 75.0% of solutions for cow, sire, herd-year-season, and group effects changed less than 4.54 kg from the previous round.

Animal Husbandry↗

PubMed1995

Antisense approaches to cancer gene therapy.

Recent advances in the use of oligodeoxynucleotide and plasmid-derived RNA as antisense agents of special relevance to cancer gene therapy are summarized with emphasis on agents and systems which have lead to clinical trials and/or regression of established tumors in animal model systems. Transformed cell lines bearing plasmids and viruses designed for the transcription of antisense RNA have the advantage that they can be characterized thoroughly and the effects of antisense RNA on target gene expression and phenotype can be studied easily in vivo. Promising results make the considerable efforts of applying oligodeoxynucleotides in whole animals and in clinical trials more plausible. Conversely, oligodeoxynucleotide experiments which yield promising results in tissue culture can be generalized to the in vivo setting by development of clones of cells bearing plasmid-derived antisense RNA against the same target. Several examples of the concordant results for oligodeoxynucleotide and plasmid-derived antisense RNA against the same target are considered. The importance of examination of antisense effects in syngeneic and immunocompetent hosts is illustrated by studies of insulin-like growth factor and insulin-like growth factor receptor where tumor regression and protection against tumor formation have been observed for particular cell types in defined settings.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Role of lateral cephalograms in assessing severity and difficulty of orthodontic cases.

To assess the role of lateral cephalometric films in the evaluation of orthodontic patients, 16 certified orthodontists examined 80 sets of dental casts and lateral cephalograms. The patients included 5 subgroups: Class I with mild crowding, Class II Division 2, Class III, open bites, and bimaxillary protrusion. A 5-point Visual Analogue Scale was used to assess the degree of severity and difficulty of each case. Severity was defined as the degree of deviation from ideal occlusion, while difficulty was defined as the probability of attaining an ideal occlusion when all treatment options were available. The examiner then chose one or more of the following treatment options: growth modification, extraction, nonextraction, and surgery. All examiners scored the degree of severity and difficulty of each case with casts only at Time 1 (T1), then with casts and cephalograms at Time 2 (T2). The observed ratings from the Visual Analogue Scale were scored by using the Rasch model, which transforms the nonlinear ordinal ratings to a linear interval scale. Intersubgroup differences and differences between T1 and T2 difficulty and severity were assessed by using a 5 x 2 repeated measures analysis of variance. A paired t test examined the amount and direction of the differences between T1 and T2 of each subgroup. Multiple contingency tables were used to compare treatment option changes between all subgroups at each time. Severity and difficulty scores highly correlated. Analysis of variance showed significant differences among subgroups for both severity and difficulty; however, there were significant time differences for severity only. Paired t tests revealed a small increase in severity for the bimaxillary protrusive group and small but significant decreases for the subgroups Class II Division 2 and Class III when cephalograms were added. The multicontingency table analysis demonstrated that a significant number of examiners did change their treatment options at T2 for bimaxillary protrusive, nonextraction, and Class II Division 2 patients. It was concluded that lateral cephalometric films showed a significant influence on a clinician's determination on severity of some types of orthodontic malocclusions.

Adolescent↗

PubMed1991

Phenotypic transformation of normal rat kidney cells: a model for studying cellular alterations in oncogenesis.

The growth characteristics of cells in culture change dramatically upon tumorigenic transformation. By the use of selective culture media supplemented with growth factor-inactivated serum, the changes in requirements for externally added polypeptide growth factors can readily be assessed. Certain nontumorigenic cell lines, including normal rat kidney (NRK) fibroblasts, can obtain the growth characteristics of a tumor cell when they became phenotypically transformed by addition of specific combinations of growth factors. This cell system provides a very attractive model for studying cellular alterations upon transformation, in particular for analyzing the molecular basis of density-dependent inhibition of growth (contact-inhibition).

Animals↗

PubMed2000

Age pattern of mortality in eight breeds of insured dogs in Sweden.

The objective of this study was to use several methods to describe the age patterns for risk of death in selected breeds of dogs insured for life in a Swedish animal-insurance company in 1996. Data on eight breeds were analyzed for age at death (including euthanasia). If dogs left the insurance for reasons other than death, they were regarded as censored. Dogs were only insured up to 10 years of age. Four analytical approaches were used. First, descriptive statistics of age distributions (e.g. breed-specific median ages at death, breed- and age-specific mortality risks) were computed. Second, age-specific estimates of survival were calculated using the formula: survival=(1-risk(age<1 year))(1-risk(age 1<2 year))... (1-risk(age 9<1 0 year)). Third, Cox regression (proportional-hazards model) was used to estimate survival and hazard functions. Finally, hierarchically coded Poisson regression was used to determine age-specific cut-points in the risk of death. The hazards from Cox and the incidence-density rates from the hierarchically coded models were transformed to estimates of risk: risk=1-exp¿-(hazard)¿ or 1-exp¿-(incidence-density rate)¿. The breeds studied were Beagle, Bernese mountain dog, Boxer, Cavalier King Charles spaniel, Drever, German shepherd dog, Mongrel and Poodle, together representing over 50000 dogs each year. The yearly breed-specific mortality risk varied between 1.7% (Poodle) and 6.5% (Bernese mountain dog). In all breeds, the risk of death increased with age but the pattern varied by breed. The probability of survival at 5 years of age varied between 94% (Cavalier King Charles spaniel and Poodle) and 83% (Bernese mountain dog, Drever, German shepherd dog) and the survival at 10 years between 83% (Poodle) and 30% (Bernese mountain dog). The survival estimates from Cox and those derived using the combined-risk formula were similar. The cut-point risk estimates provided a simplified picture of when the risk of death changed significantly compared to previous age categories. As anticipated, breeds differed widely in survival up to 10 years of age and there were marked differences in age patterns of mortality. The implications of these findings should be considered in multivariable analyses, where the confounding effect of age is often controlled for using a single age variable common to several breeds.

Age Distribution↗

PubMed2003

Shear-induced textural transitions in flow-aligning liquid crystal polymers.

The equations of nematodynamics are formulated, solved, and used to model textural transformations in sheared thermotropic flow-aligning nematic polymers. The solutions are classified and characterized using analytical, scaling, and numerical methods. It is found that as the shear rate increases, the pathway between an oriented nonplanar state and an oriented planar state is through texture formation and coarsening. The two shear-rate dependent dimensionless numbers that control the texture formation and coarsening process are Ericksen Er and Deborah De numbers. The emergence of texture is independent of the Deborah number, and occurs at Er=10(4). As the shear rate increases and Er>10(4) the first texture that arises is a defect lattice. Further increases of the shear rate bring De close to 1, ignite the coarsening processes, and replace the defect lattice with a defect gas. The smallest texture length scale l(t) occurs at the defect lattice-defect gas transition. In the defect lattice regime the texture length scale decreases with increasing shear rate as l(t) proportional to (gamma-a)(-1/2), while in the defect gas regime it increases as l(t) proportional to (gamma-b sqrt[(gamma-a)]-c)(-1). Finally when De>2, an oriented monodomain state emerges, and the texture vanishes since coarsening overpowers defect nucleation. It is found that the texture transition cascade unoriented monodomain=>defect lattice=>defect gas=>oriented monodomain is remarkably consistent with the experimentally observed textural transitions of sheared lyotropic nematic polymers.

Biophysical Phenomena↗

PubMed2002

Expression of transforming growth factor-alpha, epidermal growth factor receptor and platelet-derived growth factors A and B in oropharyngeal cancers treated by curative radiation therapy.

BACKGROUND AND PURPOSE: Epidermal growth factor receptor (EGFR) has been implicated in cellular responses to ionizing radiation and represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation existed between the expression of EGFR, transforming growth factor-alpha (TGFalpha) and platelet-derived growth factors A and B (PDGF-A and PDGF-B) and treatment outcome in a group of patients with oropharyngeal cancer who had undergone curative radiation therapy. We also assessed the relationship existing between each of the aforementioned proteins and intratumoral microvessel densities (IMD) which have been previously reported (Int J Radiat Oncol Biol Phys 2000;48:17-25. MATERIALS AND METHODS: Pretherapeutic tumor biopsies from 95 patients were immunohistochemically stained and their immunoreactivities evaluated semi-quantitatively. The statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of distant metastasis. RESULTS: Local tumor control as well as disease-free and overall survival were independent of protein expression levels, whereas combined TGFalpha and EGFR immunoreactivities were closely related to IMD (P = 0.003). The expression levels of these two proteins were also correlated to each other (P = 0.015). Expression of PDGF-B occurred in 54% of cases and was associated with an increase in the risk of developing distant metastasis (P = 0.011). CONCLUSIONS: Tumoral levels of TGFalpha, EGFR and PDGF-A/B are not predictive of radioresponsiveness in oropharyngeal cancers. The association between IMD and immunoreactivity for TGFalpha and EGFR indicates the involvement of these proteins in the promotion of angiogenesis in these tumors. PDGF-B should be further evaluated as a prognostic marker for squamous cell cancer of the head and neck.

Disease-Free Survival↗

PubMed2001

The threshold model as a general purpose normalizing transformation.

The estimation of heritabilities and genetic correlations is based on the assumption that the trait distributions are normal. When the distributions are not normal it is advisable to transform the data to produce normality. However, it is possible that no suitable transformation can be found. The purpose of the present paper is to point out that the threshold model of quantitative genetics can be used as a generalized transformation. To utilize this method it is only necessary to divide the data at the median (approximately) and code the two halves as 0 and 1. Estimates can then be made using algorithms outlined herein. A simulation study shows that the threshold transformation gave unbiased estimates of the heritability and genetic correlation in all cases. The 95% confidence limits correctly included the true heritability value in the required 95% of cases, while the estimated confidence region for the genetic correlation was also correct provided that the geometric mean heritability was greater than approximately 0.15, a restriction that applied also to the normally distributed data. Confidence intervals estimated from the non-normal data were consistently too small. The method is illustrated using data on the proportion of diapausing eggs produced by the cricket, Allonemobius socius.

Animals↗

PubMed2003

Abnormal mucosal extracellular matrix deposition is associated with increased TGF-beta receptor-expressing mesenchymal cells in a mouse model of colitis.

Transforming growth factor-beta (TGF-beta) depresses mucosal inflammation and upregulates extracellular matrix (ECM) deposition. We analyzed TGF-beta receptors RI and RII as well as ECM components using the CD4(+) T-cell-transplanted SCID mouse model of colitis. The principal change in colitis was an increased proportion of TGF-beta RII(+) mucosal mesenchymal cells, predominantly alpha-smooth muscle actin (SMA)(+) myofibroblasts, co-expressing vimentin and basement membrane proteins, but not type I collagen. TGF-beta RII(+) SMA(-) fibroblasts producing type I collagen were also increased, particularly in areas of infiltration and in ulcers. Type IV collagen and laminin were distributed throughout the gut lamina propria in disease but were restricted to the basement membrane in controls. In areas of severe epithelial damage, type IV collagen was lost and increased type I collagen was observed. To examine ECM production by these cells, mucosal mesenchymal cells were isolated. Cultured cells exhibited a similar phenotype and matrix profile to those of in vivo cells. The data suggested that there were at least two populations of mesenchymal cells responsible for ECM synthesis in the mucosa and that ligation of TGF-beta receptors on these cells resulted in the disordered and increased ECM production observed in colitic mucosa.

Activin Receptors, Type I↗

PubMed1998

Temporal dynamics of pitch strength in regular interval noises.

The pitch strength of rippled noise and iterated rippled noise has recently been fitted by an exponential function of the height of the first peak in the normalized autocorrelation function [Yost, J. Acoust. Soc. Am. 100, 3329-3335 (1996)]. The current study compares the pitch strengths and autocorrelation functions of rippled noise (RN) and another regular-interval noise, "AABB." RN is generated by delaying a copy of a noise sample and adding it to the undelayed version. AABB with the same pitch is generated by taking a sample of noise (A) with the same duration as the RN delay and repeating it to produce AA, and then concatenating many of these once-repeated sequences to produce AABBCCDD.... The height of the first peak (h1) in the normalized autocorrelation function of AABB is 0.5, identical to that of RN. The current experiments show the following: (1) AABB and RN can be discriminated when the pitch is less than about 250 Hz. (2) For these low pitches, the pitch strength of AABB is greater than that for RN whereas it is about the same for pitches above 250 Hz. (3) When RN is replaced by iterated rippled noise (IRN) adjusted to match the pitch strength of AABB, the two are no longer discriminable. The pitch-strength difference between AABB and RN below 250 Hz is explained in terms of a three-stage, running-autocorrelation model. It is suggested that temporal integration of pitch information is achieved in two stages separated by a nonlinearity. The first integration stage is implemented as running autocorrelation with a time constant of 1.5 ms. The second model stage is a nonlinear transformation. In the third model stage, the output of the nonlinear transformation is long-term averaged (second integration stage) to provide a measure of pitch strength. The model provides an excellent fit to the pitch-strength matching data over a wide range of pitches.

Acoustics↗