Perceived control

The present investigation tested the hypothesis that perceived control reduces reported symptom incidence for individuals with stressful life events. Subjects(undergraduate psychology students from an urban university) were divided into two groups, high and low in stress, based on their life change unit scores as measured by the Schedule of Recent Events(Holmes & Rahe, 1967). Subjects participated in a study in which they attempted to reduce pulse rate(PR) and were informed of their successes(i.e., PR reductions) through bogus feedback. High and low stress subjects were assigned randomly to one of the following conditions: bogus ascending success feedback(AS), wherein successes were concentrated more in the later stage of a PR reduction period; bogus equally distributed success feedback(EDS), wherein successes were equally distributed in the early and later stages of a PR reduction period; or no feedback(NF). The study consisted of three sessions held on 3 consecutive days. Each session consisted of a 3-minute baseline(nonfeedback) period followed by a 10-minute PR reduction period. Self-reports on 13 symptom items were measured 2 weeks before the study(pretest), after the final session of the study(posttest), and 3 weeks after the study(follow-up). Results indicated that on 5 of the 13 symptom items, the AS condition produced a significant reduction in reported symptom incidence for high-stress subjects only, and this effect was maintained for 3 weeks after the experiment. Results are discussed in terms of the effect perceived control may have on perceptions of physical health. Suggestions are made regarding the use of biofeedback treatment as a method by which perceptions of symptom distress may be reduced for individuals exposed to cumulative stressful experiences.     

The relative effectiveness of three techniques to induce the trophotropic response

The purpose of this study was to examine the relative effectiveness of electromyographic biofeedback training(EMG BFT), remeditation, and progressive muscle relaxation(PMR) in eliciting a relaxation or trophotropic response as measured by frontalis muscle tension, heart rate, electrodermal response, respiration rate, and skin temperature. Fifty-four college students were randomly assigned to one of five groups:(1) control,(2) placebo control,(3) EMG BFT,(4) meditation,(5) PMR. After baseline measures were obtained subjects were trained in 10 30-minute training sessions and posttested. Comparisons by ANOVAs indicated there was a significant decrease in muscle tension in the EMG BFT and meditation groups and significant decreases in respiration rate in the meditation and PMR groups. No other changes were attributed to treatment.     

Dual Role of Hydrophobic Racemic Thioesters of α-Amino Acids in the Generation of Isotactic Peptides and Co-peptides in Water; Implications for the Origin of Homochirality

Thioesters of α-amino acids are considered as plausible monomers for the generation of the primeval peptides. DL-Leucine-thioethyl esters (LeuSEt), where the L-enantiomer was tagged with deuterium atoms, undergo polycondensation in water or in bicarbonate or imidazole buffer solutions to yield mainly heterochiral (atactic) peptides and diketopiperazine, as analyzed by MALDI-TOF and ESI mass-spectrometry. In variance, when polymerization of DL(d₁₀)-Leu, first activated with N,N′-carbonyldiimidazole, then initiated with ethanethiol or with DL(d₃)-LeuSEt yielded a library of peptides up to 30 detectable residues where those of homochiral sequence (isotactic) are the dominant diastereoisomers. At these conditions, racemic β-sheets are formed and operate as stereoselective templates in the process of chain-elongation. Isotopic L:L(d₁₀)-Leu co-peptides were obtained in the polymerization of L(d₁₀)-Leu with L-LeuSEt. By contrast, mixtures of oligo-D-Leu and oligo-L(d₁₀)-Leu were obtained in the polymerization of mixtures of D-LeuSEt with activated L(d₁₀)-Leu. Isotactic co-peptides containing Leu and Val residues were formed in the polymerization of mixtures of activated DL(d₈)-Val with DL(d₃)-LeuSEt in water, implying that the racemic β-sheets exert regio-enantio-selection but not chemo-selection. A reaction pathway is suggested, where LeuSEt operates both as initiator of the reaction as well as a multimer.     

A conditioned response model of the placebo effect

A model of the placebo response as a conditioned response(CR) is presented and predictions from this model are listed. Through association with active ingredients(UCS), neutral(CS) places, persons, procedures, and things can come to acquire the ability to reduce pain, anxiety, and depressive responses. One major counterintuitive prediction from the model is that therapists who routinely use active ingredients(UCS) or powerful drugs will get stronger placebo effects than those who routinely use inert ingredients(CS) or weak drugs. Developmentally, placebo responding appears to involve two successive conditioning stages, which may involve first the left and later the right hemisphere in right-handed subjects. The relationship between placebo responding and hypnotizability is discussed.This paper was first presented at the San Diego Biomedical Symposium (invited paper), San Diego, California, November 1977. Later it was presented at a symposium on Non-Specific Effects in Biofeedback, Biofeedback Society of America, Albuquerque, New Mexico, February 1978. It has been published in abbreviated form inProceedings of the San Diego Biomedical Symposium, New York: Academic Press, 1977. I would like to thank G. E. Schwartz for encouraging me to repackage this model for left brain (critical analytic) consumers, and particularly for his encouragement and critical comments during the review process.     

A Mixed Model for Binary Data: The Modified X2-test

In this paper, a statistical model for clinical trials is presented for the special situation that a varying and unstructered number of binary responses is obtained from each subject. The assumptions of the model are the following: 1.) For each subject there is a (constant) individual Bernoulli parameter determining the distribution of the binary responses of this subject. 2.) The Bernoulli parameters associated with the subjects are realizations of independent random variables with distributions P_g in treatment group g(g = 1, 2, …, G). 3.) Given the value of the Bernoulli parameter, the observations are stochastically independent within each subject. Under these assumptions, a test statistic is derived to test the hypothesis H₀:E(P₁) = E(P₂) = … = E(P_G). It is proven and demonstrated by simulations, that the test statistic asymptotically (i.e. for a large number of subjects) follows the X²-distribution.     

Relaxation measured by EMG as a function of vibrotactile stimulation

The present study investigated the effect of vibrotactile stimulation on relaxation as measured by EMG recording. Forty-eight subjects from three age groups were randomly divided into 8 experimental groups:(1) simultaneous footrest vibration and back vibration(A ₁ C ₁ );(2) simultaneous footrest vibration and back roller(A ₁ C ₂ ); (3) simultaneous footrest vibration, back vibration and back roller(A ₁ C ₃ ); (4) footrest vibration alone(A ₁ C ₄ ); (5) back vibration alone(A ₂ C ₁ ); (6) back roller alone(A ₂ C ₂ ); (7) simultaneous back vibration and back roller(A ₂ C ₃ ); and(8) control group (no vibration/stimulation)(A ₂ C ₄ ). The three major variables studied were footrest vibration(A ₁ andA ₂ ), pre- and post-EMG measures(B ₁ andB ₂ ), and back vibration(C ₁ C ₂ C ₃ C ₄ ). Results showed that footrest vibration had a significant effect on relaxation. Other conditions (except the control) produced a decrease in EMG levels, but did not reach significance. Pre- and postmeasures by experimental conditions were also significantly different. Application of vibration as an aid in relaxation is discussed.Research supported by the Niagara Therapy Mfg. Co.     

Markov branching processes with varying growth rates

A branching processZ(t) which behaves as Markov branching processesZ ₁(t) andZ ₂(t) during the free and dead times of a counter process is considered. Expression forE[Z(t)] is given.     

Molecular characterization,recombinant expression in <Emphasis Type="Italic">Escherichia coli</Emphasis> and biological activity of (<Emphasis Type="Italic">S</Emphasis>)-Tetrahydroberberine oxidase from <Emphasis Type="Italic">Corydalis saxicola</Emphasis> Bunt

(S)-Tetrahydroberberine [(S)-THB] oxidase is the last enzyme of benzylisoquinoline alkaloids pathway which catalyzes the dehydrogenation of four hydrogen atoms of (S)-THB to produce berberine, the final step of berberine biosynthesis. A (S)-THB gene, designated as Cs(S)-THBO (Genbank accession No. HQ393909), was cloned from a Corydalis saxicola cDNA library by rapid amplification of cDNA ends. The full-length of cDNA of Cs(S)-THBO was 1127 bp with an open reading frame of 699 bp that predicted to encode a 232-amino acid polypeptide, with a predicted molecular mass of 25.20 kDa. Cs(S)-THBO was the first (S)-THBO gene found in C. saxicola. Real-time quantitative PCR analysis indicated that Cs(S)-THBO was constitutively expressed in roots, stems, leaves and flowers of C. saxicola, and with the highest expression level in roots. The results of treatment experiment for plant defense responses revealed that expression of Cs(S)-THBO had a prominent diversity. Recombinant Cs(S)-THBO protein expressed in Escherichia coli strain BL21 (DE3) was active. The results of feeding experiment and HPLC–DAD–ESI–MSⁿ analysis showed that Cs(S)-THBO had the function of catalyzing (S)-tetrahydroberberine to berberine.     

Optimal Fixing of the Bandwidth-Parameter for the Empirical Regression1,2

The estimator ?₀(x) of the regression r(x) = E (Y | × = x) from measured points (x_i, y_i), i = 1(1) n, of a continuous two-dimensional random variable (X, Y) with unknown continuous density function f(x, y) and with moments up to the second order can be made with the help of a density estimation f?₀(x, y) (see e.g. SCHMERLING and PEIL, 1980). Here f?₀(x, y) still contains free parameters (so-called band-width-parameters), the values of which have to be optimally fixed in the concrete case. This fixing can be done by using a modification of the maximum-likelihood principle including jackknife techniques. The parameter values can be also found from the estimators for r(x). Here the cross-validation principle can be applied. Some numerical aspects of these possibilities for optimally fixing the bandwidth-parameter are discussed by means of examples. If ?₀(x) is used as a smoothing operator for time series the optimal choice of the parameter values is dependent on the purpose of application of the smoothed time series. The fixing will then be done by considering the so-called filter-characteristic of ?C₀(x).     

Conflicting results in EEG alpha feedback studies

Success or failure of EEG feedback training for alpha enhancement can depend on how alpha activity is quantified and fed back. Alpha-enhancement failures usually employ a percent time(%) technique; successes typically use amplitude integration(). To dramatize the differences between percent and integration techniques, we derived both measures simultaneously from left occipital(O ₁ ) and left central(C ₃ ) sites for 16 male subjects who were given 5.6 hours of integrated alpha feedback from the midline occipital(O_z ) site. At both the O ₁ and C ₃ sites the integrated and percent measures were not equivalent and not linearly related. Statistically significant differences in the(integrated, percent) correlation coefficients(z-transformed) were observed under the different recording conditions: alpha enhancement, alpha enhancement, alpha suppression, and baselines. Theoretical discussion of integration and percent techniques is given and the adoption of amplitude integration measures and feedback stimuli is strongly advocated.This study was supported by the following grants and contracts: National Institute of Mental Health (NIMH) Predoctoral Fellowship #1 F01 MH51704-01, NIMH General Research Support Grant #LPNI 185, and a Langley Porter Neuropsychiatric Institute Postdoctoral Fellowship (Interdisciplinary Training Program, NIMH #7082) to James V. Hardt, and by NIMH Research Scientist Development Award 2K02 MH38897, NIMH Research Grant #1 R01 MH24820, Office of Naval Research (ARPA) Contract N00014-70-C-0350, and Instruction and Research Funds, Computer Center Accounts (UCSF) #1431 and #1437 to Joe Kamiya.     

ALGORITHM FOR APPLICATION OF FOURIER ANALYSIS FOR BIORHYTHMIC BASELINES OF PHARMACODYNAMIC INDIRECT RESPONSE MODELS

The change of an indirect pharmacological response R(t) can be described by a periodic time-dependent production rate k_in (t) and a first-order loss constant k_out. If k_in(t) follows some biological rhythm (e.g., circadian), then the response R(t) also displays a periodic behavior. A new approach for describing the input function in indirect response models with biorhythmic baselines of physiologic substances is introduced. The present approach uses the baseline (placebo) response R_b(t) to recover the equation for k_in(t). Fourier analysis provides an approximate equation for R_b(t) that consists of terms (usually two or three) of the Fourier series (harmonics) that contribute most to the overall sum. The model differential equation is solved backward for k_in(t), yielding the equation involving R_b(t). A computer program was developed to perform the square L²-norm approximation technique. Fourier analysis was also performed based on nonlinear regression. Cortisol suppression after inhalation of fluticasone propionate (FP) was modeled based on the inhibition of the secretion rate k_in(t) using ADAPT II. The pharmacodynamic parameters k_out and IC₅₀ were estimated from the model equation with k_in(t) derived by the new approach. The proposed method of describing the input function needs no assumption about the behavior of k_in(t), is as efficient as methods used previously, and is more flexible in describing the baseline data than the nonlinear regression method. (Chronobiology International, 17(1), 77–93, 2000)     

α-Hydroxyphosphonate Oligonucleotides: A Promising DNA Type?

Abstract

The synthesis of monomers ( S )-1, ( R )-1 and 2 derived from (5′ S )-, (5′ R )-2′-deoxythymidine-5′-C-phosphonic acids and 2′,5′-dideoxythymidine-5′-C-phosphonic acids was elaborated. The protection of the 5′-hydroxyl by the methoxycarbonyl group was a key step of the synthesis. Prepared monomers were used for the solid-phase assembly of several types oligothymidylate 15-mers ( S )-3, ( S )-4, ( S )-5, ( R )-4 and ( R )-5 containing the chiral 3′-O-P-CH(OH)-5″ internucleotide linkage. Their hybridization properties with dA₁₅ and rA₁₅ were studied as well as their resistance against nuclease cleavage.     

Novel genes influencing the expression of the yellow locus and mdg4 (gypsy) in Drosophila melanogaster

Summary We used a system with a mobilized Stalker transposable element, sometimes in combination with P-M hybrid dysgenesis, in the search for new mutations interfering with the y ² mutation induced by mdg4 (gypsy) insertion into the yellow locus. A novel gene, modifier of mdg4, was detected in chromosome 3. The mutation mod(mdg4) either enhanced or suppressed phenotypic changes in different mutations induced by mdg4 insertions. Thus, mod(mdg4) seems to be involved in the control of mdg4 expression. Six other loci designated as enhancers of yellow were also detected. The e(y) ⁿ (with n from 1–6) mutations enhanced the expression of several y mutations induced by different insertions into the yellow locus. The major change is a damage of bristle and hair pigmentation which is not suppressed by su(Hw) mutations. On the other hand, e(y) ⁿ alleles do not interact with mdg4 induced mutations in other loci. All e(y) ⁿ genes are located in different regions of the X chromosome. One may speculate that e(y) ⁿ genes are involved in trans-regulation of the yellow locus and possibly of some other loci.     

A visualization of 3D proteome universe: Mapping of a proteome ensemble into 3D space based on the protein-structure composition

To visualize a bird’s-eye view of an ensemble of proteomes for various species, we recently developed a novel method of mapping a proteome ensemble into Three-Dimensional (3D) vector space. In this study, the “proteome” is defined as the entire set of all proteins encoded in a genome sequence, and these proteins were dealt with at the level of the SCOP Fold. First, we represented the proteome of a species s by a 1053-dimensional vector x(s), where its length ∣x(s)∣ represents the overall amount of all the SCOP Folds in the proteome, and its unit vector x(s)/∣x(s)∣ represents the relative composition of the SCOP Folds in the proteome and the size of the dimension, 1053, is the number of all possible Folds in the proteome ensemble given. Second, we mapped the vector x(s) to the 3D vector y(s), based on the two simple principles: (1) ∣y(s)∣ = ∣x(s)∣, and (2) the angle between y(s) and y(t) maximally correlates with the angle between x(s) and x(t). We applied to the mapping of a proteome ensemble for 456 species, which were retrieved from the Genomes TO Protein structures and functions (GTOP) database. As a result, we succeeded in the mapping in that the properties of the 1053-dimensional vectors were quantitatively conserved in the 3D vectors. Particularly, the angles between vectors before and after the mapping highly correlated with each other (correlation coefficients were 0.95–0.96). This new mapping method will allow researchers to intuitively interpret the visual information presented in the maps in a highly effective manner.     

Baseline levels in muscle relaxation training

Variations in the baseline levels of physiological measures, a familiar problem in psychophysiological research, can affect the results of clinical applications and research in the self-control of bodily processes. In this presentation, the problem is illustrated within the context of skeletal muscle relaxation training using continuous biofeedback(BF) based on surface electromyographic(EMG) activity. In terms of the Law of Initial Values(LIV), higher EMG levels are expected to be associated with greater decreases during training. The combined results of two studies documented an LIV-like effect for pretraining baseline levels with greater EMG decreases after training for subjects with the higher pretraining baselines. Left uncorrected, such baseline differences were shown to lead to discrepant results between two identical studies, and therefore to conflicting conclusions about the effectiveness of these procedures. The available methods suggested to correct for the biasing effect of baseline differences in research are described, with particular emphasis on the analysis of covariance.This research was supported in part by NIH Grants MH24222 and AI-10398. The authors would like to thank Miss Sharon Robinson for supervising the collection of data and for her constructive comments regarding the training procedures of the studies described.     

Di-<Emphasis Type="Italic">tert</Emphasis>-butylsilylene-directed α-selective synthesis of <Emphasis Type="Italic">p</Emphasis>-nitrophenyl T-antigen analogues

Seven analogues of p-nitrophenyl T-antigen [Galβ(1→3)GalNAcα(1→O)PNP] have been synthesized as potential substrates for elucidation of the substrate specificity of endo-α-N-acetylgalactosaminidase. These compounds, which are commercially unavailable, include: GlcNAcβ(1→3){GlcNAcβ(1→6)}GalNAcα(1→O)PNP [core 4 type], GalNAcα(1→3)GalNAcα(1→O)PNP [core 5 type], GlcNAcβ(1→6)GalNAcα(1→O)PNP [core 6 type], GalNAcα(1→6)GalNAcα(1→O)PNP [core 7 type], Galα(1→3)GalNAcα(1→O)PNP [core 8 type], Glcβ(1→3)GalNAcα(1→O)PNP and GalNAcβ(1→3)GalNAcα(1→O)PNP. The assembly of these synthetic probes was accomplished efficiently, based on di-tert-butylsilylene(DTBS)-directed α-galactosylation as a key reaction.     

A New Functional Equation Analogous to CAUCHT-PEXIDER Functional Equation and its Application

The CAUCHY-PEXIDER functional equation H (x±y)=F(x) G(y) is generalized to the form H ((x^c±y^c)^1/c) = F(x) G(y), c≠0, assuming the function H(x) possesses a measurable majorant on a set of positive measure. The result is used to obtain a characterization of WEIBULL distribution. This functional equation is generalized to functions of vector variables.     

Mechanism of suppression inDrosophila: Regulation of tryptophan oxygenase by thesu(s) + allele

The suppressor gene,su(s)², inDrosophila melanogaster restores the production of red and brown eye pigments for some purple and vermilion mutant alleles, respectively. We showed previously that the product of thesu(s)⁺ allele caused inhibition of the sepiapterin synthase A produced by the purple mutant but did not affect the wild-type enzyme. Suppression was accomplished by removingsu(s)⁺ from the genome. We now report that the tryptophan oxygenase, produced by suppressible vermilion alleles, is also inhibited by extracts fromsu(s)⁺ flies. The inhibition of the vermilion enzyme can be reduced or eliminated, respectively, by prior storage of the extract at 4 or –20°C or by boiling, whereas the wild-type enzyme is not affected by extracts ofsu(s)⁺ flies. Also, when the suppressible vermilion strain is raised on certain diets, brown eye pigment production occurs. This epigenetic suppression was reduced by the presence of an extra copy ofsu(s)⁺ in the genome. These data support a posttranslational mechanism for regulation of enzyme activity in which the activity of the mutant enzyme is reduced by the product of thesu(s)⁺ allele. How thesu(s)⁺ gene product can distinguish between the normal and the mutant forms of these two enzymes is discussed, along with other mechanisms for suppression that are currently under investigation.This work was supported in part by a grant from the KOSEF, Korea Science and Engineering Foundation, and the National Science Foundation under the U.S.-East Asia Cooperative Science Program as well as the Office of Health and Environmental Research, U.S. Department of Energy, under Contract DE-AC05-840R21400 with the Martin Marietta Energy Systems, Inc.     

Microwave-Assisted Synthesis of 2(1H)-Pyridones and Their Glucosides as Cell Proliferation Inhibitors

A new series of substituted 2(1H)-pyridones (4a–i) and their glucosides (5, 6a–e) were prepared as potential agents against leukemia (HL-60) cells. Glucosides (5,6a–e) were synthesized using three independent methods. Microwave protocol as an ecologically new method was used to synthesize the target compounds. Structures of the new products were confirmed using one- and two-dimensional NMR spectroscopy. In vitro exposure of pyridones substituted at position 4 with a 2-thienyl or 2-(trifluoromethyl)phenyl were found to exhibit high antiproliferation activities; in particular, 3-cyano-4-(thien-2′-yl)-6-(4″-chlorophenyl)-2(1H)-pyridone (4c) and its glucoside analogue (6c) had the highest activity.