Standard Functional Analysis Research Articles

Identity and divergence of protein domain architectures after the yeast whole-genome duplication event

Gene duplication is a key mechanism in evolution for generating new functionality, and it is known to have produced a large proportion of genes. Duplication mechanisms include small-scale, or "local", events such as unequal crossing over and retroposition, together with global events, such as chromosomal or whole genome duplication (WGD). In particular, different studies confirmed that the yeast S. cerevisiae arose from a 100-150 million-year old whole-genome duplication. Detection and study of duplications are usually based on sequence alignment, synteny and phylogenetic techniques, but protein domains are also useful in assessing protein homology. We develop a simple and computationally efficient protein domain architecture comparison method based on the domain assignments available from public databases. We test the accuracy and the reliability of this method in detecting instances of gene duplication in the yeast S. cerevisiae. In particular, we analyze the evolution of WGD and non-WGD paralogs from the domain viewpoint, in comparison with a more standard functional analysis of the genes. A large number of domains is shared by genes that underwent local and global duplications, indicating the existence of a common set of "duplicable" domains. On the other hand, WGD and non-WGD paralogs tend to have different functions. We find evidence that this comes from functional migration within similar domain superfamilies, but also from the existence of small sets of WGD and non-WGD specific domain superfamilies with largely different functions. This observation gives a novel perspective on the finding that WGD paralogs tend to be functionally different from small-scale paralogs. WGD and non-WGD superfamilies carry distinct functions. Finally, the Gene Ontology similarity of paralogs tends to decrease with duplication age, while this tendency is weaker or not observable by the comparison of the domain architectures of paralogs. This suggests that the set of domains composing a protein tends to be maintained, while its function, cellular process or localization diversifies. Overall, the gathered evidence gives a different viewpoint on the biological specificity of the WGD and at the same time points out the validity of domain architecture comparison as a tool for detecting homology.

Generalized eigenfunctions of layered elastic media and application to diffuse fields

The spectral decomposition of the elastic wave operator in a layered isotropic half-space is derived by means of standard functional analysis methods. Particular attention is paid to the coupled P-SV waves. The problem is formulated directly in terms of displacements which leads to a 2 x 2 Sturm-Liouville system. The resolvent kernel (Green's function) is expressed in terms of simple plane-wave solutions. Application of Stone's formula leads naturally to eigenfunction expansions in terms of generalized eigenvectors with oscillatory behavior at infinity. The generalized eigenfunction expansion is employed to define a diffuse field as a white noise process in modal space. By means of a Wigner transform, we calculate vertical to horizontal kinetic energy ratios in layered media, as a function of depth and frequency. Several illustrative examples are considered including energy ratios near a free surface, in the presence of a soft layer. Numerical comparisons between the generalized eigenfunction summation and a classical locked-mode approximation demonstrate the validity of the approach. The impact of the local velocity structure on the energy partitioning of a diffuse field is illustrated.

A reply

We would like to reply to comments made by Kozek-Langenecker and Scharbert regarding our article on fluid-related side-effects on standard coagulation tests and functional hemostasis analyses in children. The authors criticised the fact that albumin, gelatine and hydroxyethyl starch 130/0.4 (HES) were all administered at equal amounts of 15 ml.kg−1 and stated that the known difference in volume-expanding effects of these solutions would explain the reported findings. We are aware of the different volume-expanding effects of the tested solutions, which, however, are primarily related to differences in molecular size, and thus differences in elimination. We therefore performed analyses immediately after administration in order to avoid pronounced influences of volume expansion. Moreover, as shown in our Table 1, the results of concentration-dependent analyses (Hb, platelet count, fibrinogen concentration, AT, FXIII) declined similarly after administration of all fluids, thus confirming a comparable dilutional state. The authors further asked about the rationale for choosing fibrinogen/fibrin polymerisation (FIBTEM® MCF) for sample size calculation and mentioned that this variable did not significantly differ after gelatine or HES 130/0.4 administration. FIBTEM® MCF was chosen because previous studies have clearly demonstrated that colloids primarily interfere with fibrinogen/fibrin polymerisation, especially at the dilutional stage investigated by us. It is correct that direct comparison showed no statistically significant difference for gelatine vs hydroxyethyl starch with regard to fibrinogen/fibrin polymerisation, but this was also true for hydroxyethyl starch vs albumin, while no difference was observed between albumin and gelatine. In addition, the α angle was significantly lower for HES than for albumin, while no difference was observed for gelatine. CT values were prolonged only for HES. Moreover, speed of clot formation was significantly prolonged for HES as compared to albumin or gelatine. The authors also stated that no treatment of impaired haemostasis was needed. However, this assumption refers only to the immediate post-infusion period, while several children, of course, needed administration of coagulation factors and even platelets during their further intra-operative course. As the need for haemostatic therapy was beyond the aim of the study, we did not provide these data. Lastly, the authors mentioned that the newer starches should impair coagulation to a lesser extent than do the older starches, as used in the referenced study by Wilkes. Nevertheless, recent published works prompt questions on this topic [1, 2], and further data will be needed to finally answer the question as to the intrinsic effects of the various HES solutions.

Bayesian Hierarchical Spatially Correlated Functional Data Analysis with Application to Colon Carcinogenesis

In this article, we present new methods to analyze data from an experiment using rodent models to investigate the role of p27, an important cell-cycle mediator, in early colon carcinogenesis. The responses modeled here are essentially functions nested within a two-stage hierarchy. Standard functional data analysis literature focuses on a single stage of hierarchy and conditionally independent functions with near white noise. However, in our experiment, there is substantial biological motivation for the existence of spatial correlation among the functions, which arise from the locations of biological structures called colonic crypts: this possible functional correlation is a phenomenon we term crypt signaling. Thus, as a point of general methodology, we require an analysis that allows for functions to be correlated at the deepest level of the hierarchy. Our approach is fully Bayesian and uses Markov chain Monte Carlo methods for inference and estimation. Analysis of this data set gives new insights into the structure of p27 expression in early colon carcinogenesis and suggests the existence of significant crypt signaling. Our methodology uses regression splines, and because of the hierarchical nature of the data, dimension reduction of the covariance matrix of the spline coefficients is important: we suggest simple methods for overcoming this problem.

Functional analysis skills training for residential caregivers

AbstractFunctional analysis is the most effective assessment for identifying the maintaining contingencies of aberrant behavior. However, it is suggested that functional analyses are not conducted regularly due to the level of skill required. A multiple baseline design across participants was used to assess if four residential caregivers, with limited experience with applied behavior analysis, could be trained to implement the standard analog functional analysis conditions. The training consisted of a lecture, written information, modeling, rehearsal, and feedback. Results showed that all participants attained percentage correct responding scores above 95% on three consecutive trials following training. One caregiver showed positive generalization of skills to the assessment of another behavioral topography. The result of this study provides further evidence that lay individuals can be trained to assist in conducting functional analyses. Copyright © 2008 John Wiley & Sons, Ltd.

Functional optical signal analysis: a software tool for near-infrared spectroscopy data processing incorporating statistical parametric mapping

Optical topography (OT) relies on the near infrared spectroscopy (NIRS) technique to provide noninvasively a spatial map of functional brain activity. OT has advantages over conventional fMRI in terms of its simple approach to measuring the hemodynamic response, its ability to distinguish between changes in oxy- and deoxy-hemoglobin and the range of human participants that can be readily investigated. We offer a new software tool, functional optical signal analysis (fOSA), for analyzing the spatially resolved optical signals that provides statistical inference capabilities about the distribution of brain activity in space and time and by experimental condition. It does this by mapping the signal into a standard functional neuroimaging analysis software, statistical parametric mapping (SPM), and forms, in effect, a new SPM toolbox specifically designed for NIRS in an OT configuration. The validity of the program has been tested using synthetic data, and its applicability is demonstrated with experimental data.

Minimum Angular-Impulse Control for a Large Flexible Spacecraft

Characterization and implementation of efficient rotational motions of flexible spacecraft have been of research interest for more than 20 years. In the present study we consider rest-to-rest pointing maneuvers for a very large spacecraft, so that limits on available angular momentum are paramount. A formal system of differential equations is developed based on a model that includes a rigid central hub and Euler-Bernoulli appendages. The model is recast in an appropriate state-space and standard functional analysis methods are used to prove well-posedness and to establish a framework for numerical approximation. Several variants of minimum-angular moment problems are studied; ultimately, we focus on a low-dimensional control parameterization based on a family of versine functions and on quasi-static structural response. Results are characterized in terms of simple formulas and sensitivity with respect to problem data is presented.

Galerkin method and approximate tracking in a non-minimum phase bilinear system

The tracking control of non-minimum phase systems is nowadays an open and challenging field, because a general theory is still not available. This article proposes an indirect control strategy in which a key role is played by the inverse problem that arises and their approximate solutions. These are obtained with the Galerkin method, a standard functional analysis tool. A detailed study of the effect on the output caused by the use of an approximate input is performed. Error bounds are also provided. The technique is motivated through its implementation in basic, DC-to-DC nonlinear power converters that are intended to be used as DC-to-AC voltage sources.

A PARADOXICAL EFFECT OF PRESESSION ATTENTION ON STEREOTYPY: ANTECEDENT ATTENTION AS AN ESTABLISHING, NOT AN ABOLISHING, OPERATION

Previous studies have shown that presession attention for problem behavior can serve as an abolishing operation when attention functions as a positive reinforcer. In the current study, we show that the stereotypy of a child with severe disabilities was undifferentiated during standard analogue functional analysis conditions. However, when noncontingent presession attention was provided, stereotypy occurred for social attention as a positive reinforcer, suggesting that the antecedent manipulation functioned as an establishing operation.

A functional analysis and treatment of the irrational and rational statements of an elderly woman with Alzheimer's disease

Speech problems are a hallmark of Alzheimer's disease. Although often attributed to neurological damage common to the disease speech problems have been successfully treated through the use of behavior analytic techniques. This study was a replication and extension of that line of research. The participant in this study was an elderly woman diagnosed with Alzheimer's who was referred for services due to frequent irrational statements and infrequent rational statements. Both standard functional analysis and modified functional analysis conditions were conducted. It appeared the irrational statements were controlled by social reinforcement. Several treatment packages consisting of differential reinforcement of incompatible behaviors and extinction components were implemented in an ABCDEAE treatment design. Results of the study suggest the intervention successfully increased rational statements but had no effect on irrational statements. These results indicate the need for further research on the conditions under which behavior analysis techniques will be most effective. Copyright © 2006 John Wiley & Sons, Ltd.

Functional analysis and treatment of low rate problem behavior in individuals with developmental disabilities

AbstractExtensive research has validated the standard functional analysis as a useful technology for identifying the function of problem behavior in individuals with developmental disabilities. The assessment of low rate problem behavior is one area that has yet to receive a significant amount of research. Some problem behaviors may occur at rates too low to be observed during a standard functional analysis, despite the fact that they may be highly destructive behaviors. The current study evaluated the effectiveness of initiating functional analysis sessions contingent on the occurrence of bursts of problem behavior for producing interpretable functional analysis results. While a standard functional analysis did not produce definitive results with respect to behavioral function, the ‘low rate’ functional analysis produced interpretable results for all three participants. Two of the three participants were available for the evaluation of treatments based on their functional analysis results. Function‐based treatments suppressed rates of problem behavior for both participants. Copyright © 2004 John Wiley & Sons, Ltd.

Abnormal Gut Fermentation: Laboratory Studies reveal Deficiency of B vitamins, Zinc, and Magnesium

Gut fermentation in the colon is a normal phenomenon whereby soluble non‐starch polysaccharides are metabolized to short‐chain fatty acids. Abnormal fermentation may be associated with clinical symptoms and is generally assumed to take place in the small bowel. It may be established by ethanol production after a sugar challenge in the fasting subject, which produces maximum production of ethanol 1 hour after sugar challenge. This timing is compatible with the dose acting in the small bowel, but not the large. It was noted that patients with abnormal gut fermentation established by gut fermentation ethanol production tests tended to have low levels of vitamins and minerals, and it was therefore decided to make a prospective study of patients with the condition to determine if this was so.Patients were tested for ethanol production together with standard functional analysis techniques for vitamins B1, B2, and B6 and zinc and magnesium concentrations by sweat analysis using air/acetylene flame atomic absorption. Fifty normal subjects (group A) were analyzed against 30 positive patients by alcohol testing (group B). Statistical analysis, using the Wilcoxon Sum of Ranks test, revealed a remarkable and consistently high difference for vitamins and minerals between the two groups. In group B, 19 of 30 patients had four of five or five of five nutrients abnormal, and no subject with a positive alcohol test had less than two abnormal nutrients.It is concluded that the syndrome that causes abnormal gut fermentation appears to have adverse effects on levels of B vitamins, zinc, and magnesium. As yet it is not clear whether this is a result of malabsorption, over‐utilization, or excessive excretion. The level of ethanol production in this condition is low, but the presence of the nutritional deficits implies that the syndrome may cause quite significant adverse effects on health. More research in this area is required to replicate and extend these studies.

Functional analysis and treatment of low‐rate problem behavior in individuals with developmental disabilities

AbstractExtensive research has validated the standard functional analysis as a useful technology for identifying the function of problem behavior in individuals with developmental disabilities. The assessment of low‐rate problem behavior is one area that has yet to receive a significant amount of research. Some problem behaviors may occur at rates too low to be observed during a standard functional analysis, despite the fact that they may be highly destructive behaviors. The current study evaluated the effectiveness of initiating functional analysis sessions contingent on the occurrence of bursts of problem behavior for producing interpretable functional analysis results. While a standard functional analysis did not produce definitive results with respect to behavioral function, the ‘low‐rate’ functional analysis produced interpretable results for all three participants. Two of the three participants were available for the evaluation of treatments based on their functional analysis results. Function‐based treatments suppressed rates of problem behavior for both participants. Copyright © 2004 John Wiley & Sons, Ltd.

Functional analysis of precurrent contingencies between mands and destructive behavior.

Functional analysis methods have greatly enhanced our ability to assess, understand, and treat problem behavior. However, standard functional analysis methods that assess whether problem behavior is maintained by social positive reinforcement (e.g., attention, tangible items), social negative reinforcement (e.g., escape from demands), and automatic reinforcement (e.g., sensory reinforcement, pain reduction) can produce inconclusive results and fail to identify idiosyncratic functions in up to 40% of cases. One such idiosyncratic function involves a precurrent contingency between destructive behavior and a child's mands (usually spoken requests). In this paper, I discuss this unique function of destructive behavior and a specific functional analysis method my colleagues and I have developed to analyze its precurrent relation to a child's mands. We hypothesize that destructive behavior may become a precurrent response for a child's mands because the two responses produce reinforcement more accurately and consistently than either or both responses could if they were operating on the environment independent of one another. ********** STANDARD FUNCTIONAL ANALYSES Functional analysis is a set of methods used to (a) identify the environmental contexts in which aberrant behavior is likely and unlikely to occur, (b) determine the contingencies that maintain aberrant behavior, and (c) prescribe effective treatments. Although several earlier studies examined the effects of a single environmental variable on problem behavior (e.g., escape; Carr, Newsom, & Binkoff, 1980), the inception of functional analysis can be attributed to the seminal work by Iwata and colleagues (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994). What set this analysis apart from previous investigations was its comprehensive approach to analyzing the function of self-injurious behavior (SIB). Iwata and colleagues developed an experimentally sound method to analyze the three operant hypotheses for SIB described by Carr (1977). Carr suggested that SIB might occur because it resulted in attention from caregivers (social positive reinforcement), or because it resulted in escape from nonpreferred activities (social negative reinforcement), or because it produced sensory stimulation (automatic positive reinforcement). Iwata et al. (1982/1994) developed an analogue (test) condition for each of these hypotheses and compared the levels of SIB in each test condition with a control condition using a multielement design. Each condition consisted of a discriminative stimulus (Sd), an establishing operation (EO), and a consequence for the target behavior (SIB). In the attention condition, the test condition for social positive reinforcement, the therapist sat in a chair, reading a magazine (the Sd), and ignored the individual (the EO), but provided attention contingent only on occurrences of SIB (the consequence). If SIB was reinforced by attention, then the rates of this behavior would tend to be higher in this test condition than in the control condition. In the demand condition, which served as the test condition for social negative reinforcement, the room was furnished with work materials (the Sd), the individual was prompted to complete nonpreferred tasks or demands (the EO), and the demands were terminated following occurrences of SIB (the consequence). If SIB was reinforced by escape from nonpreferred demands, then rates of SIB would tend to be higher in this test condition than in the control condition. In the test condition for automatic positive reinforcement, the individual was alone in a room (the Sd), no toys, leisure materials, or other forms of stimulation were availa ble (the EO), and SIB resulted only in whatever stimulation it produced automatically (the consequence). If SIB was reinforced by the stimulation it produced automatically, its rates should be higher in this test condition because there were no competing forms of stimulation available. …

Noncontingent attention for the treatment of excessive medical complaints in a medically fragile man with mental retardation

Providing medical care to individuals with developmental disabilities who have medical problems may pose several challenges with regard to accurate and reliable report of symptoms. In addition, medical complaints may take on operant functions such as an attention function or an escape function as a result of the natural consequences in the environment. It may be difficult to withhold reinforcers for medical complaints such as attention or escape, making a standard analog functional analysis or extinction-based intervention less appropriate. Recent studies have shown that noncontingent reinforcement without extinction and noncontingent reinforcement using alternative reinforcers can be effective in reducing problem behavior. One practical implication of these findings is that noncontingent reinforcement may be an appropriate treatment in cases where the reinforcer responsible for behavioral maintenance cannot be identified or withheld. In the current study, attention served as a reinforcer for a young man with medical complaints and noncontingent attention without ignoring effectively reduced the participant’s excessive medical complaints.

Interpreting functional analysis results using the real‐time recording of independent and dependent variables

An extended series of functional analysis conditions were conducted to assess the operant function of aggressive behaviors emitted by a 33-year-old female with diagnoses of severe mental retardation and organic psychosis. Results from the primary test conditions were fairly undiAerentiated, but response rates were elevated in the control condition. Independent-variable integrity data from the control condition indicated that aggressive behaviors were nearly always contiguous with the fixed-time delivery of experimenter attention. These results are discussed in the context of the current control condition functioning as a possible test for escape from social interaction. #1998 John Wiley & Sons, Ltd. Behav. Intervent., Vol. 13, 61‐66 (1998) Standard functional analysis test conditions usually include sessions designed to assess the reinforcing qualities of attention, task escape, sensory stimulation (via a no-interaction condition) and occasionally tangible items (Iwata, Pace, Dorsey, Zarcone, Vollmer, & Smith, 1994). Additionally a control or ‘play’ condition can be implemented as a control with which other conditions are compared. Theoretically, the control condition is a ‘noncontingent’ reinforcement treatment package, designed to provide noncontingent attention (usually delivered on a fixed-time basis), noncontingent breaks (a total absence of demands), noncontingent tangible items (continuous access to toys or leisure materials), and to some degree noncontingent sensory stimulation. The aforementioned stimulus conditions typically result in low response rates. Elevated responding in the control condition generally occurs when the behavior is maintained by sensory stimuli or some unknown factor (e.g., physiological

Beurling's Theorem for the Bergman space

Beurling's Theorem for the Bergman space

Abnormal gut fermentation: Laboratory studies reveal deficiency of B vitamins, zinc, and magnesium

Gut fermentation in the colon is a normal phenomenon whereby soluble non-starch polysaccharides are metabolized to short-chain fatty acids. Abnormal fermentation may be associated with clinical symptoms and is generally assumed to take place in the small bowel. It may be established by ethanol production after a sugar challenge in the fasting subject, which produces maximum production of ethanol 1 hour after sugar challenge. This timing is compatible with the dose acting in the small bowel, but not the large. It was noted that patients with abnormal gut fermentation established by gut fermentation ethanol production tests tended to have low levels of vitamins and minerals, and it was therefore decided to make a prospective study of patients with the condition to determine if this was so. Patients were tested for ethanol production together with standard functional analysis techniques for vitamins B 1, B 2, and B 6 and zinc and magnesium concentrations by sweat analysis using air/acetylene flame atomic absorption. Fifty normal subjects (group A) were analyzed against 30 positive patients by alcohol testing (group B). Statistical analysis, using the Wilcoxon Sum of Ranks test, revealed a remarkable and consistently high difference for vitamins and minerals between the two groups. In group B, 19 of 30 patients had four of five or five of five nutrients abnormal, and no subject with a positive alcohol test had less than two abnormal nutrients. It is concluded that the syndrome that causes abnormal gut fermentation appears to have adverse effects on levels of B vitamins, zinc, and magnesium. As yet it is not clear whether this is a result of malabsorption, over-utilization, or excessive excretion. The level of ethanol production in this condition is low, but the presence of the nutritional deficits implies that the syndrome may cause quite significant adverse effects on health. More research in this area is required to replicate and extend these studies.