Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk.

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to <20% of the world's population. We used transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock.

An examination of graduate students' statistical judgments: statistical and fuzzy set approaches.

The present study examined how statistical significance levels are treated and interpreted by graduate students who use hypothesis-testing in their scientific investigation. To test underlying psychological aspects of hypothesis-testing, the idea of fuzzy set theory was employed to identify the uncertain points in judgments. 34 graduate students in a psychology department made judgments about hypothetical statistical decisions. The results indicated that (1) the majority of these students treated significance levels on a continuum and rated them according to the magnitude of statistical significance; (2) the subjects shifted their decisions based on the types of hypothetical scenarios but not by the sample sizes; instead, they interpreted a smaller sample size as being less reliable. (3) The subjects frequently chose formally used statistical terms, e.g., Significant and Not Significant, more than graduated verbal expressions, e.g., Marginally Significant and Borderline Significant; and (4) the Fuzziness (degree of confidence in decision-making) was dependent on individuals and existed more in the critical points of transition where judgments are most difficult. The Fuzziness Index illustrated the subtle shifts of human decision-making patterns in statistical judgments. Underlying decision uncertainties and difficulties can be illustrated by functions generated from fuzzy set theory, which may more closely resemble human psychological mechanism. This integrative study of fuzzy set theory and behavioral measurements appears to provide a technique that is more natural for examining and understanding imprecise boundaries of human decisions.

Increasing the reliability of Wechsler Intelligence Scale for Children--Third Edition difference scores with reliable component analysis.

Wechsler Intelligence Scale for Children--Third Edition index score differences are generally interpreted cautiously, if at all, primarily because of their poor reliability. On the basis of prior analyses with the Wechsler Adult Intelligence Scale--Third Edition (J. C. Caruso & N. Cliff, 1999), it was hypothesized that differences between scores defined by reliable component analysis would have higher reliability than those defined by traditional equal weighting. Differences between the reliable component scores showed substantially higher reliability than equally weighted score differences. The differences between reliable component scores were also substantially more reliable than those derived from the weighted scores suggested by K. C. H. Parker and L. Atkinson (1994). Using the weights provided in this article will allow researchers and practitioners to compute the RCA scores and have the assurance of high reliability with its attractive consequences.

The Factor Structure of the WAIS-R: Replicability Across Age-Groups.

This article examines the factor structure of the Wechsler Adult Intelligence Scale- Revised across nine age groups using several methods of factor analysis, including reliable component analysis (RCA). RCA defines orthogonal components which have maximum reliability, and has several desirable properties which are discussed. Although the one- factor model (General Intelligence, or g), and the two-factor model (Verbal and Performance) of the WAIS-R are fairly well established. no such consensus has been reached regarding the three-factor model (Verbal Comprehension. Perceptual Organization, and Freedom from Distractibility). In the present study, g and Verbal and Performance factors were consistent across age groups for most methods of extraction, although somewhat different from the usual division. The three-factor model, however, was not consistently identified across age groups by any method, particularly with respect to Freedom from Distractibility. Meaningful interpretation of scores on this factor is therefore tenuous. RCA performed well, relative to most other methods, in identifying factors consistently across age groups and can provide useful and unique information.

Answering Ordinal Questions with Ordinal Data Using Ordinal Statistics.

It is argued that ordinal statistical methods are often more appropriate than their more common counterparts for three types of reasons: Conclusions from them will be unaffected by monotonic transformation of the variables, they are statistically more robust when used appropriately, and they often correspond more closely to the goals of the investigator. Kendall's tau (Kendall, 1970) and its counterpart delta are recommended as having wide I applicability and good statistical behavior. It is recommended that they be estimated as population parameters and their standard errors estimated form the data. Ways in which they can then substitute for Pearson correlations and mean comparisons in a number of research contexts are suggested.

Redundant leading and following zeros in comparative numerical judgment.

The objective was to provide a more comprehensive understanding of how people make numerical comparative judgments when digits are contained in numbers with redundant leading or following zeros, e.g., 00080 and 800.000. These sequences of numbers often appear on computer display terminals (VDT) as line numbers, but surprisingly little research has been done on this. The experiment manipulated three aspects of numerical stimuli: (1) redundant leading zeros, (2) redundant following zeros, and (3) length of string of digits. The subjects were to push one of the two button-switches to respond whether two stimulus numbers shown on the computer screen were equal or unequal. The target stimuli contained several forms of redundant zeros, and each performance was assessed by response RT of the subjects. Analysis indicated five significant findings: (1) Redundant leading zeros hindered performance, (2) The effect of redundant following zeros depended on the stimulus type, (3) Over-all, longer digits took more processing time, (4) The RTs for the second-block trials were significantly faster than the first, and (5) Task performance was facilitated when the redundant zero representations were identical in both stimuli of a pair. Nonlexicographic processing seems to occur when feature identification can be used for numerical identification, that is, when the format is consistent. The research has implications for those in computer science to provide numerical formats which make comparative judgments as easy as possible.

Analysis of pattern-reversal visual evoked-potential topography: replicability in normal subjects and comparisons with Alzheimer's disease.

This paper reports two studies using multivariate analysis to aid the interpretation of cross-coherence of multiple electrode sites in evoked potential responses. In the first study, the replicability of principal components and multidimensional scaling was evaluated by applying both methods to pattern-reversal visual evoked potentials recorded from 28 scalp sites in two subgroups of sex- and age-matched healthy subjects, and then comparing the results. Four dimensions replicated in the two initial multidimensional scaling solutions and appeared to reflect differences in: 1) anterior versus posterior scalp areas, 2) laterality, 3) separation of frontal and occipital sites from other scalp regions, and 4) proximal versus distal placements. The initial principal components did not match well in the two groups, but rotation to congruence improved their replicability and ultimately yielded axes similar to those of the multidimensional scaling dimensions. In the second study, Alzheimer's disease and sex- and age-matched control subjects were evaluated. The four axes identified were the same as those described above, but after the solutions were rotated to align them, the group differences appeared negligible. Examination of the components and dimensions from both studies showed some consistent departures from being merely reflectors of site location, and the apparently visual dimension appeared clearly in all four groups. Judged on the basis of initial interpretability and replicability of the solutions, the results suggest that multidimensional scaling, with appropriate transformation, may provide an effective tool for analyzing pattern-reversal visual evoked-potential topography.

Principal components and multidimensional scaling of auditory and visual event-related potential topography.

Principal components analysis and metric multidimensional scaling were used to assess auditory and visual event-related potential topography in healthy late-middle-aged and elderly adults (n = 20). Binaurally elicited auditory evoked potentials and full-field checkerboard pattern reversal visual event-related potentials were recorded from 28 scalp sites. The zero-lag, cross-correlations of all waveforms for 300 msec post-stimulus epochs were obtained and separate analyses of the auditory and visual data were performed. Ultimately, three of the four dimensions identified in the principal components and multidimensional scaling solutions were similar and represented electrode site differences in (1) the anterior-posterior plane; (2) laterality; and, (3) the proximal-distal relation to midline. The remaining multidimensional scaling axis appeared to reflect effects specific to the modality of stimulation. Under auditory stimulation, the temporal and central-parietal sites were distinct from other scalp regions, whereas under visual stimulation, the occipital and frontal sites were distinctive. Although the results of the principal component analyses were conceptually similar to the multidimensional scaling outcomes, there were consistent differences between them. The findings provide empirical support for the validity of these multivariate methods in topographic analysis.

Variances and Covariances of Kendall's Tau and Their Estimation.

We generalize the formulas derived by Daniels and Kendall (1947) for the variance of the sample tau correlation. It is assumed that multivariate data are sampled from a population, and sample taus between pairs of variables are being used to estimate their population counterparts. Expressions for the variance of tau-a are generalized to allow for ties on either variable, and we further provide an expression for the covariance between two taus, including the special case where there is a variable in common. Unbiased estimators of the variance and the covariances are also derived for use in small samples. The variances and covariances of tau-a are used to provide asymptotic variances for tau-b and Somers' d.

Using the longitudinal Guttman simplex as a basis for measuring growth.

Many difficulties inherent in the measurement of growth stem from the use of traditional measurement methodologies. The longitudinal Guttman simplex (LGS), an alternative approach based on a model of growth, is discussed in this article. The LGS has several advantages over traditional methodology. First, interindividual differences in developmental rates are a part of the model. Second, the LGS procedure can easily handle any number of occasions of measurement. Third, the LGS is suited to nonlinear as well as linear monotonic growth. Fourth, a consistency index associated with the LGS methodology, CL, indicates the extent to which cumulative, unitary development characterizes a particular latent variable. Finally, and perhaps most important, because a model of the growth undergone by the latent variable being measured is incorporated in the LGS model the resulting instruments enjoy a high level of construct validity. The LGS is limited to cumulative, unitary development; additional measurement theories are needed for other kinds of development.

Factor Recovery in Binary Data Sets: A Simulation.

The present study compares the performance of phi coefficients and tetrachorics along two dimensions of factor recovery in binary data. These dimensions are (a) accuracy of nontrivial factor identification, and (b) factor structure recovery given a priori knowledge of the correct number of factors to rotate. Nontrivial factor identification was poor for both indices, with phi's performing slightly better than tetrachorics. In contrast, factor structure recovery was quite good when the correct number of factors was rotated. Phi coefficients generally yielded better factor structure recovery than tetrachorics and were better at preventing items from intruding onto factors where they did not belong, while tetrachorics were better than phi's at preventing items from being omitted from factors where they should have been included. The solutions based on tetrachorics contained many Heywood cases. It is suggested that for most applications it is preferable to base factor analysis on phi coefficients.

Patterns of Crime in a Birth Cohort.

Most attempts at developing typologies of criminal behavior have not involved empirical research. This paper describes an exploratory empirical approach to identifying patterns in criminal behavior. Two data-reduction techniques, factor analysis and cluster analysis, are applied to the official arrest records of a Danish birth cohort of 28,879 men. Four factors emerged from the factor analysis: GENERAL CRIME, TRAFFIC OFFENSES, WHITE-COLLAR CRIME, and SEX OFFENSES. The cluster analysis revealed GENERAL CRIME and TRAFFIC OFFENSES clusters. A substantial number of offenses are shown by both analyses to be independent of any pattern. The results show good split-sample cross-validation and for the most part are robust across the two analytic approaches.

Some Cautions Concerning The Application Of Causal Modeling Methods.

Literal acceptance of the results of fitting "causal" models to correlational data can lead to conclusions that are of questionable value. The long-established principles of scientific inference must still be applied. In particular, the possible influence of variables that are not observed must be considered; the well-known difference between correlation and causation is still relevant, even when variables are separated in time; the distinction between measured variables and their theoretical counterparts still exists; and ex post facto analyses are not tests of models. There seems to be some danger of overlooking these principles when complex computer programs are used to analyze. correlational data, even though these new methods provide great increases in the rigor with which correlational data can be analyzed.

THE INVESTIGATION OF COGNITIVE MODELS FOR INVENTORY RESPONSE.

This research centers around a family of models designed to describe individuals' responses to personality inventory responses. The models are all alternative ways of relating the individual's degree of endorsement of the items to their locations on dimensions of semantic meaning as he perceives them. In the present study, the relationships among individuals' responses to adjective check list items and multidimensional scaling analyses of similarity judgments of the same items were studied. For each individual, a multiple correlation was computed between his endorsement of the items and their locations on dimensions. The median R, corrected for the number of predictors, was .81 in the case of "candid" endorsements and .92 for endorsements under a faking set. These correlations are comparable to the consistencies in endorsement across repetitions of the same items. Implications for a personality measurement theory are discussed.