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PubMed1985

Effect of indoor lighting on normal skin.

A small but measurable component of some indoor lighting is ultraviolet radiation (UVR); whether it is sufficient to modify the indoor worker's risk for chronic skin changes is not directly answerable with available technology. A first approach to this question involves a) estimating a range of annual background solar exposure for indoor workers currently at risk; b) determining whether, and at what levels, UVR exposure is a part of specified indoor lighting; and c) calculating the increment in risk implied by a and b. This algorithm predicts that some lighting conditions that meet NIOSH recommended standards would still result in significant increases in the risk of cumulative UVR damage, including skin cancer. More information concerning actual exposure conditions, the relation of spectral effectiveness for luminosity and UVR production, and dose-time reciprocity are required to improve our predictions of long-term cutaneous effects of indoor lighting.

Erythema↗

PubMed1979

Acoustic invariance in speech production: evidence from measurements of the spectral characteristics of stop consonants.

On the basis of theoretical considerations and the results of experiments with synthetic consonant-vowel syllables, it has been hypothesized that the short-time spectrum sampled at the onset of a stop consonant should exhibit gross properties that uniquely specify the consonantal place of articulation independent of the following vowel. The aim of this paper is to test this hypothesis by measuring the spectrum sampled at the onsets and offsets of a large number of consonant-vowel (CV) and vowel-consonant (VC) syllables containing both voiced and voiceless stops produced by several speakers. Templates were devised in an attempt to capture three classes of spectral shapes: diffuse-rising, diffuse-falling, and compact, corresponding to alveolar, labial, and velar consonants, respectively. Spectra were derived from the utterances by sampling at the consonantal release of CV syllables and at the implosion and burst release of VC syllables, and these spectra (smoothed by a linear prediction algorithm) were matched against the templates. It was found that about 85% of the spectra at initial consonant release and at final burst release were correctly classified by the templates, although there was some variability across vowel contexts. The spectra sampled at the implosion were not consistently classified. A preliminary examination of spectra sampled at the release of nasal consonants in CV syllables showed a somewhat lower accuracy of classification by the same templates. Overall, the results support an hypothesis that, in natural speech, the acoustic characteristics of stop consonants, specified in terms of the gross spectral shape sampled at the discontinuity in the acoustic signal, show invariant properties independent of the adjacent vowel or of the voicing characteristics of the consonant. The implication is that the auditory system is endowed with detectors that are sensitive to these kinds of gross spectral shapes, and that the existence of these detectors helps the infant to organize the sounds of speech into their natural classes.

Humans↗

PubMed1985

Excretory urography in current practice: evidence against overutilization.

Excretory urography could be performed less frequently if some combinations of genitourinary signs and symptoms were found to be predictive of either a specific disease or normality. To explore this possibility, the authors conducted a prospective study involving more than 3,000 patients at three institutions (a teaching hospital, a community hospital, and a health maintenance organization). Predictive algorithms were obtained by application of a polychotomous logistic regression model but did poorly at differentiating normal from abnormal patients or arriving at a specific diagnosis. Selection of patients on the basis of the logistic model would have required testing 90% of all patients in order to detect 95% of those with abnormal urograms. These results suggest that current clinical selection criteria for excretory urography are effective, and that present frequency of utilization is appropriate.

Diagnosis, Differential↗

PubMedDate not supplied

Molecular modeling of protein-glycosaminoglycan interactions.

Forty-nine regions in 21 proteins were identified as potential heparin-binding sites based on the sequence organizations of their basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to formulate two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for glycosaminoglycan recognition were determined as [-X-B-B-X-B-X-] and [-X-B-B-B-X-X-B-X-] where B is the probability of a basic residue and X is a hydropathic residue. Predictions were then made as to the heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs show prominent amphipathic periodicities having both alpha-helical and beta-strand conformations as determined by predictive algorithms and circular dichroism studies. The heparin-binding domain of vitronectin was modeled and formed a hydrophilic pocket that wrapped around and folded over a heparin octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of polyanions in proteins and may provide a useful guide in identifying heparin-binding regions in other proteins. The possible relevance of protein-glycosaminoglycans interactions in atherosclerosis is discussed.

Algorithms↗

PubMedDate not supplied

Comparison of drug dosing methods.

The literature reviewed herein clearly demonstrates the poor correlation between drug dosing and the ability to achieve a specific serum drug concentration and between drug dosing and clinical response, especially for drugs with a narrow therapeutic index. There is, however, a better correlation between serum drug concentration and observed clinical response. Thus, clinicians use serum drug concentrations to more accurately dose drugs. Numerous dosing methods have been developed in an attempt to improve the relationship between dosing, serum drug concentration, and response. The major hypothesis is that if dosing methods can be developed that will accurately predict serum drug concentrations, these methods would be useful in improving clinical care. Several dosing methods have been developed including use of 'standard' doses, population-based predictive algorithms and nomograms, pharmacokinetic equations, and Bayesian feedback. Some of these methods are accurate and useful, whereas others are not. This review evaluates the commonly used dosing methods (some of which utilise serum drug concentration feedback for dosage estimation) for 5 drugs: gentamicin, digoxin, phenytoin, theophylline, and lignocaine (lidocaine). These drugs were selected since they exhibit a representative cross section of pharmacokinetic parameters and since they exhibit a representative cross section of pharmacokinetic parameters and since they have narrow therapeutic ranges. An individualised method and a Bayesian method, both using serum drug concentration feedback, appear most accurate and precise in dosing to achieve desired serum drug concentrations and, hence, response. Our bias from personal experience with this method and from published use by others is that the Bayesian method is more flexible in that any number of serum drug concentrations may be used to determine dose, instead of the 3 or more required for the individualised method. Although use of these methods would appear to be cost-effective in timely provision of health care by reduction of toxicity and hospital stay, only sparse data have been generated to support this conclusion. Thus, further examination of the cost-effectiveness of drug dosing methods is necessary to establish their place in routine patient care.

Costs and Cost Analysis↗

PubMed2026

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

PubMed1992

Analysis of the amino acid sequence of the Pseudomonas aeruginosa galactophilic PA-I lectin.

Based on the NH2-terminal 30-amino acid sequence of Pseudomonas aeruginosa galactophilic PA-I lectin, two degenerate primer oligonucleotides were synthesized and used in polymerase chain reaction with the bacterial chromosomal DNA as a template. A predominant DNA fragment of the appropriate size was radiolabeled and used as a probe for screening a P. aeruginosa genomic lambda gt11 library. One positive clone carrying an insert of about 630 base pairs encompassing the entire PA-I lectin gene was isolated and found to contain a 369-base pair open reading frame between an initiation codon (19 base pairs downstream from the insertion site, subsequent to a Shine-Dalgarno sequence) and two consecutive stop codons, followed by an oligo (seven) A sequence, in a partial dyad symmetry. The deduced amino acid sequence shows excellent agreement with the quantitative amino acid analysis and a perfect match with the NH2-terminal amino acid sequence of the purified lectin. It reveals that the PA-I lectin subunit contains 121 amino acids (M(r) 12,754; pI 4.94) with a predominant central hydrophilic core between two hydrophobic domains. Secondary structure algorithms predict that it is rich in beta sheets and contains several highly antigenic epitopes, but no signal peptide. In the carboxyl region a potential glycosylation site (Asn-Asn-Ser) was identified. Comparative analyses of this lectin sequence with those of lectins from other sources, reported in the protein and gene data banks, did not reveal any extensive homology.

Adhesins, Bacterial↗

PubMedDate not supplied

Epitopic characterization and vaccinal potential of peptides derived from a major antigen of Schistosoma mansoni (Sm28 GST).

The P28 antigen of Schistosoma mansoni has been shown to induce protective immunity against schistomiasis in rodents and primates. The analysis of the primary structure of the P28 molecule using various predictive algorithms led to the synthesis of seven peptides which were used to localize the major T cell epitopes of the P28. Two of these synthetic peptides (amino acids 24-43 and 115-131) were found to contain major T cell sites of the P28 antigen. Indeed, both 24-43 and 115-131 peptides stimulate T lymphocytes from Fischer rats and Balb/c mice immunized with the recombinant P28. Moreover, these localized moieties are exposed to the host's immune system during natural S. mansoni infection since they activate T cell populations of infected rats, mice and chronically infected Kenyan children. A multiple antigen peptide containing eight copies of peptide (MAP 115-131) has been prepared and used as immunogen in rats, mice and baboons. In all these models, the MAP 115-131 induces both humoral and cellular responses towards the P28. Preimmunization with the MAP 115-131 before a challenge with the whole P28 molecule increases T cell proliferation and antibody production. The active immunization of rats with the MAP 115-131 before a challenge with the whole P28 molecule increases the T cell proliferation and the antibody production. The active immunization of rats with the MAP 115-131 before challenge infection with the parasite achieved significant protection.

Amino Acid Sequence↗

PubMedDate not supplied

[Features of structure-activity organization of prolactin].

The secondary structure of seven hormones of the prolactin family was predicted by two known prediction algorithms with the following averaging of the results for the whole homologous group of proteins. It was shown that the mentioned hormones are related to the alpha-helical type of protein molecules. The comparative analysis of the prolactin family and the kindred growth hormone family has been carried out on different levels of their structural organization. A conclusion is drawn, that despite the significant differences in the primary structures and small differences in the secondary structures, the three-dimensional structure for the prolactin molecules and the growth hormone are very similar and repeat in the same way the packing of alpha-helices. The study of the relationship of the prolactin structure and function has been carried out. The regions of the amino acid sequence, able to form prolactin antigenic sites and conditionally incorporated into two highly specific spatial groups were revealed. The region of the primary structure 80-137 determining lactogenic and proliferational function of the molecule and forming the alpha-hairpin in the tertiary structure has been discovered. The structural particuliarity of one of the binding sites of prolactin and human growth hormone with lactogenic receptor was reveal. An explanation for the absence of lactogenic activity in all kinds of growth hormones except human ones has been proposed.

Amino Acid Sequence↗

PubMed1987

A serine protease (CCP1) is sequestered in the cytoplasmic granules of cytotoxic T lymphocytes.

Based upon the use of a new predictive algorithm, three peptides were synthesized that correspond to likely antigenic sites of the cytotoxic T cell-specific protease cytotoxic cell protein 1 (CCP1). Antibodies raised against these peptides, under reducing conditions, bound to a single protein of m.w. 29,000 found in two actively cytotoxic T cells. This protein was absent from a "cytotoxic" T cell line that had lost its cytolytic properties. By using immunocytologic techniques, the protein was localized within cytoplasmic granules. In addition, granules purified from the cytoplasm of cytotoxic T cells were shown, by Western blot analysis, to contain the protein. The molecule detected by the antibodies behaves, upon reduction, similarly to a diisopropylfluorophosphate-binding protein. Thus, here we provide evidence that CCP1, a protein whose expression correlates with cytotoxicity, is contained within organelles which have been implicated in killing. These findings strongly suggest that CCP1 plays a key role in T cell-mediated target cell lysis.

Cell Line↗

PubMed1989

Secondary structure and limited three-dimensional structure of bovine amelogenin.

Secondary structural features of bovine amelogenin, a hydrophobic protein of developing enamel implicated in ename mineralization, are derived using 2D NMR spectroscopy in solution and molecular mechanics-dynamics studies. A beta-turn: beta-sheet model with some "unordered" segments was previously proposed from circular dichroism, Fourier-transform infrared and Raman spectroscopy augmented by Chou-Fasman predictive algorithm. The proposed structure contains a repetitive beta-turn segment, "beta-spiral" between Gln112 and Leu138 residues containing a (Pro, Leu, Gln) rich segment. The beta-spiral structure offers a probable site for interaction of Ca++ ions. Assignment of proton resonances using 2D COSY spectroscopy is presently in progress. Preliminary 2D NOESY spectra have revealed the presence of Tyr residues (TRAP segment) on the surface of amelogenin molecule and clusters of cross peaks reminiscent of beta-turns and sheets which are consistent with the primary structure and proposed secondary structures of amelogenin. The channel-like beta-spiral structure embedded in amelogenin provides a novel mechanism for trapping of Ca++ ions and their passage for a hydrophobic protein sparse in Ser(P) and charged amino acid residues.

Amelogenin↗

PubMed1986

Secondary structure prediction of human SAA1. Presumptive identification of calcium and lipid binding sites.

Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is an acute phase protein thought to be the precursor of amyloid fibrils in reactive systemic (AA) amyloidosis. A prediction of the secondary structure of the human serum amyloid protein SAA1(alpha) is presented. The prediction was based upon one-dimensional Fourier analysis of the amino acid sequence together with sequence matching to known structural motifs. The results were compared with those from prediction algorithms based upon statistical techniques. Our findings are consistent with available experimental data. They include the putative identification of the amino-terminal 11 residues as the functionally important lipid-binding site of SAA and of a likely, neutral, calcium-binding sequence: Gly48-Pro49-Gly50-Gly51. Sequence comparisons between SAA and protein tyrosine kinases, phospholipases A2 and delta-crystallin, all of which bind both calcium and phospholipid, revealed significant homologies that support our proposals concerning structure-function relationships in SAA.

Animals↗

PubMed1987

Automated serial ECG-analysis within an epidemiological study.

Since 1980 we have performed a cohort study in order to develop diagnostic and predictive algorithms for myocardial infarction. These algorithms shall be based on cardiovascular risk factors, ECG-measurements and serial measurement changes. An intermediate analysis of 5524 study participants describes observed measurement changes stratified by age and sex. The values thus obtained may serve for reference purposes and illustrate the influence of age and sex on intraindividual ECG-measurement changes. Specific suggestions are made for future program developments in order to overcome some present problems in serial ECG-analysis.

Age Factors↗

PubMed1985

Structural studies of phosvitin in solution and in the solid state.

Phosvitin, a highly phosphorylated glycoprotein, represents the major fraction of hen egg yolk phosphoproteins. Circular dichroism, Fourier transform infrared spectroscopy, and Fourier transform infrared photoacoustic and fluorescence spectroscopic methods were employed to determine the secondary structure of the protein in both the solid and solution phases. This was supplemented by a Chou-Fasman type of predictive algorithm for the first 25 residues at the N terminus of the dephosphorylated protein. A three-compartment model consisting of alpha-helical, beta-sheet, and beta-turn components with beta-turns occurring at the interface between alpha-helical and beta-sheet regions in the proximity of O-phosphoserine residues is suggested from the combined analyses. Beta-sheets appear to be the dominant secondary structural component in phosvitin in the solid and solution phases. The suggested model bears many similarities to other phosphoproteins reported in the literature. The secondary structure of phosvitin is observed to be sensitive to environmental factors as previously reported although the present studies differ in some respects from earlier results. Preliminary results suggest that Ca2+ ions trigger a decrease in beta-sheet structure at pH 2.

Amino Acid Sequence↗

PubMed1985

Application of the log-linear and logistic regression models in the prediction of systemic lupus erythematosus in the dog.

This study sought to mathematically define canine systemic lupus erythematosus (SLE) by unifying diagnostic criteria proposed by others. Thirty-one cases of canine SLE were selected for modeling when 4 different published schemes agreed on the diagnosis, and 122 controls were selected when a patient's status met no scheme's criteria. The log-linear method showed an association between SLE and polyarthritis, hematologic abnormalities, renal damage, dermatologic disorders, and antinuclear antibody test response (positive). Logistic regression was then used to derive a predictive algorithm that could identify cases and controls with which all published criteria would be in accordance. The final equation correctly classified 93.5% of the affected dogs and 98.4% of the controls. It was concluded that the log-linear and logistic regression models are useful for the diagnosis of clinically similar, but distinguishable, disease states.

Animals↗

PubMed1978

The primary structure of the nonpolar segment of bovine cytochrome b5.

The primary structure of the membrane bound segment of amphipathic bovine liver microsomal cytochrome b5 has been determined. This 43 residue nonpolar polypeptide is present at the COOH terminus of cytochrome b5. The sequence was obtained by automated sequence analysis and carboxypeptidase digestions. The sequence obtained is: Ile-Thr-Lys-Pro-Ser-Glu-Ser-Ile-Ile-Thr-Ile-Asp-Ser-Asn-Pro-Ser-Trp-Trp-Thr-Asn-Trp-Leu-Ile-Pro-Ala-Ile-Ser-Ala-Leu-Phe-Val-Ala-Leu-Ile-Tyr-His-Leu-Tyr-Thr-Ser-Glu-Asn. Conformational analysis using predictive algorithms is presented along with circular dichroism data on the peptide bound to phospholipid vesicles.

Amino Acid Sequence↗

PubMed1978

[Predictive studies in psychopharmacology (author's transl)].

Once the efficacy of a drug has been proven (by controlled trials), it may be interesting to define "responder" and "non-responder" profiles. This can be done with a non-comparative prediction trial in which initial (pre-treatment) characteristics of subjects with good or poor result are compared, or with a randomized trial in which one attempts to define initial features of favorable or unfavorable cases, which could lead later to a better choice for a future given patient between these therapies (and only these ones) given in similar conditions. Predictor variables can be: demographic, physiologic, nosologic, symptomatic. Statistical methods can be: simple comparison of responses between sub-classes according to one initial feature, or multivariate techniques particularly discriminant analysis (when results are expressed in a dichotomic way), multiple regression (when responses are graded, as with an improvement score). Validation of results of such trials can be done by checking their predictive value on subjects independant of those from which prediction algorithms have been set up.

Adult↗

PubMed1987

An improved algorithm for the prediction of optimum and suboptimum folding structures of long single-stranded RNA.

We have previously reported an algorithm (Yamamoto and Yoshikura, 1985) for the prediction of optimum and suboptimum RNA folding structures. The calculation data was presented as an 'information map'. However, the result was affected by the starting point of calculation. In this paper, we have improved the method so that the result will not be affected by the starting point. In addition, we present a method of converting the information map into a set of pictures of optimal and suboptimal molecular structures.

Algorithms↗