Showing papers by "University of California, San Diego published in 1982"
TL;DR: A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures.
21,921 citations
TL;DR: A model in which developmental regulation of RNA processing is used to increase the diversity of neuroendocrine gene expression is proposed.
Abstract: Alternative processing of RNA transcripts from the calcitonin gene results in the production of distinct mRNAs encoding the hormone calcitonin or a predicted product referred to as calcitonin gene-related peptide (CGRP). The calcitonin mRNA predominates in the thyroid while the CGRP-specific mRNA appears to predominate in the hypothalamus. These observations lead us to propose a model in which developmental regulation of RNA processing is used to increase the diversity of neuroendocrine gene expression.
2,030 citations
TL;DR: To assess bacterioplankton production in the sea, a procedure for measuring growth based on incorporation of tritiated thymidine into DNA is developed; the accuracy of this procedure was tested under a variety of laboratory and field conditions.
Abstract: To assess bacterioplankton production in the sea, we have developed a procedure for measuring growth based on incorporation of tritiated thymidine into DNA; the accuracy of this procedure was tested under a variety of laboratory and field conditions. By autoradiography, we have found that for all practical purposes our technique is specific for the nonphotosynthetic bacteria and that virtually all of the “active” bacteria (one-third or more of the total countable bacteria) take up thymidine. We also measured (1) the intracellular isotope dilution of thymidine assessed by parallel experiments with labeled phosphorus, and (2) DNA content of natural marine bacteria (0.2 to 0.6 μm size fraction); a conversion factor derived from these data permitted estimation of production from thymidine incorporation results. A very similar conversion factor was independently derived from the empirical relationship between thymidine incorporation and growth of natural bacterioplankton under controlled conditions. Combined results show that this technique, which can be performed rapidly and easily at sea, provides good estimates of production. Data from Southern California Bight waters, which contain oligotrophic as well as moderately eutrophic regions, show that average bacterioplankton doubling times, like those of the phytoplankton, are on the order of a few days, with fastest growth at depths just below those of greatest phytoplankton abundance. Offshore bacterial production is roughly 5 to 25% of the primary production; thus, at a 50% assimilation efficiency, the bacterioplankton would consume 10 to 50% of the total fixed carbon.
1,495 citations
TL;DR: RNA viruses show high mutation frequencies partly because of a lack of the proofreading enzymes that assure fidelity of DNA replication, and high rates of replication reflected in rates of RNA genome evolution which can be more than a millionfold greater than the rates of the DNA chromosome evolution of their hosts.
Abstract: RNA viruses show high mutation frequencies partly because of a lack of the proofreading enzymes that assure fidelity of DNA replication. This high mutation frequency is coupled with high rates of replication reflected in rates of RNA genome evolution which can be more than a millionfold greater than the rates of the DNA chromosome evolution of their hosts. There are some disease implications for the DNA-based biosphere of this rapidly evolving RNA biosphere.
1,394 citations
TL;DR: A DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone was microinjected into the pronuclei of fertilized mouse eggs, and seven mice developed that carried the fusion gene and six of these grew significantly larger than their littermates.
Abstract: A DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone was microinjected into the pronuclei of fertilized mouse eggs. Of 21 mice that developed from these eggs, seven carried the fusion gene and six of these grew significantly larger than their littermates. Several of these transgenic mice had extraordinarily high levels of the fusion mRNA in their liver and growth hormone in their serum. This approach has implications for studying the biological effects of growth hormone, as a way to accelerate animal growth, as a model for gigantism, as a means of correcting genetic disease, and as a method of farming valuable gene products.
1,306 citations
TL;DR: When two signals are presented, responses are faster than separate-activation models can explain, and the results favor “coactivation” models, in which signals presented on different channels contribute to a common pool of activation that initiate a response.
1,159 citations
TL;DR: Observations confirm that the distal stump influences proximal regeneration and indicate that this influence can act only over a limited distance or volume.
607 citations
TL;DR: A model for the control of the hands and fingers during typing based upon an Activation-Trigger-Schema system in which a hierarchical structure of schemata directs the selection of the letters to be typed and, then, controls the hand and finger movements by a cooperative, relaxation algorithm.
550 citations
TL;DR: An error-based method called weak mutation testing is described, in which tests are constructed which are guaranteed to force program statements which contain certain classes of errors to act incorrectly during the execution of the program over those tests.
Abstract: Different approaches to the generation of test data are described. Error-based approaches depend on the definition of classes of commonly occurring program errors. They generate tests which are specifically designed to determine if particular classes of errors occur in a program. An error-based method called weak mutation testing is described. In this method, tests are constructed which are guaranteed to force program statements which contain certain classes of errors to act incorrectly during the execution of the program over those tests. The method is systematic, and a tool can be built to help the user apply the method. It is extensible in the sense that it can be extended to cover additional classes of errors. Its relationship to other software testing methods is discussed. Examples are included.
481 citations
TL;DR: The results show that wounds in the brain of developing or adult rats stimulate the accumulation of neuronotrophic factors and that the activity of these factors increases over the first few days after infliction of the damage.
Abstract: A cavity was made in the brain (entorhinal cortex) of developing or adult rats, and a small piece of Gelfoam was emplaced to collect fluid secreted into the wound. The neuronotrophic activity of the fluid was assayed with sympathetic and parasympathetic neurons in culture. The results show that wounds in the brain of developing or adult rats stimulate the accumulation of neuronotrophic factors and that the activity of these factors increases over the first few days after infliction of the damage.
476 citations
TL;DR: The probability distribution of the phase angle between two vectors perturbed by correlated Gaussian noises is studied in detail and its asymptotic behavior for large signal-to-noise for "small," "near \pi/2 ," and "large" angles is found.
Abstract: The probability distribution of the phase angle between two vectors perturbed by correlated Gaussian noises is studied in detail. Definite integral expressions are derived for the distribution function, and its asymptotic behavior for large signal-to-noise is found for "small," "near \pi/2 ," and "large" angles. The results are applied to obtain new formulas for the symbol error rate in MDPSK, to calculate the distribution of instantaneous frequency, to study the error rate in digital FM with partial-bit integration in the postdetection filter, and to obtain a simplified expresion for the error rate in DPSK with a phase error in the reference signal. In the degenerate case in which one of the vectors is noise free, the results lead to the symbol error rate in MPSK.
TL;DR: In this paper, the effects of flow inhomogeneities on the dynamics of laminar flamelets in turbulent flames, with account taken of influences of the gas expansion produced by heat release, were investigated.
Abstract: To study effects of flow inhomogeneities on the dynamics of laminar flamelets in turbulent flames, with account taken of influences of the gas expansion produced by heat release, a previously developed theory of premixed flames in turbulent flows, that was based on a diffusive-thermal model in which thermal expansion was neglected, and that applied to turbulence having scales large compared with the laminar flame-thickness, is extended by eliminating the hypothesis of negligible expansion and by adding the postulate of weak-intensity turbulence. The consideration of thermal expansion motivates the formal introduction of multiple-scale methods, which should be useful in subsequent investigations. Although the hydrodynamic-instability mechanism of Landau is not considered, no restriction is imposed on the density change across the flame front, and the additional transverse convection correspondingly induced by the tilted front is described. By allowing the heat-to-reactant diffusivity ratio to differ slightly from unity, clarification is achieved of effects of phenomena such as flame stretch and the flame-relaxation mechanism traceable to transverse diffusive processes associated with flame-front curvature. By carrying the analysis to second order in the ratio of the laminar flame thickness to the turbulence scale, an equation for evolution of the flame front is derived, containing influences of transverse convection, flame relaxation and stretch. This equation explains anomalies recently observed at low frequencies in experimental data on power spectra of velocity fluctuations in turbulent flames. It also shows that, concerning the diffusive-stability properties of the laminar flame, the density change across the flame thickness produces a shift of the stability limits from those obtained in the purely diffusive-thermal model. At this second order, the turbulent correction to the flame speed involves only the mean area increase produced by wrinkling. The analysis is carried to the fourth order to demonstrate the mean-stretch and mean-curvature effects on the flame speed that occur if the diffusivity ratio differs from unity.
TL;DR: The life quality of patients with COPD was found to be impaired relative to healthy subjects on all dimensions; depression was the preponderant emotional disturbance reported; difficulties with home management and reduction in social interaction were the primary social-role deficits.
Abstract: • Two hundred three patients with hypoxemic chronic obstructive pulmonary disease (COPD) and 73 healthy control subjects matched for age, sex, race, and neighborhood of residence were administered three self-report inventories concerned with the following four dimensions of life quality: emotional functioning, social-role functioning, activities of daily living, and recreational pastimes. An additional inventory was administered to a spouse or another close relative of each patient. The life quality of patients with COPD was found to be impaired relative to healthy subjects on all dimensions. Depression was the preponderant emotional disturbance reported; difficulties with home management and reduction in social interaction were the primary social-role deficits. Ambulation, mobility, sleep and rest, and a variety of recreational pastimes were also severely affected. Life quality exhibited moderate but significant relationships to neuropsychological, pulmonary, and cardiac functioning and to exercise capability. Age and socioeconomic status were found to be possible moderators of the relationship of COPD to life quality. A model to integrate these findings is proposed. Implications for the management of COPD and for the evaluation of medical treatments of chronic disabling conditions are described. (Arch Intern Med1982;142:473-478)
TL;DR: Results suggest that both the Golgi apparatus and the microtubule-organizing center may participate in directing cell movement, and are discussed in the light of previous hypotheses and experimental evidence concerning cell motility.
Abstract: We have used the technique of experimental wounding of confluent monolayers of normal fibroblasts to induce essentially unidirectional and synchronous cell movement at the edge of the wound. The intracellular location of the Golgi apparatus and the microtubule-organizing center was determined by double indirect immunofluorescence microscopy, using antibodies specific for the membranes of the Golgi apparatus and antibodies specific for tubulin, respectively. In cells at the wound edge, the immunolabeled Golgi apparatus and microtubule-organizing center were in close proximity to one another and located predominantly forward of the cell nucleus facing the wound. In the same cultures in cells removed from the wound, the two organelles were also coordinately located; however, they were randomly oriented with respect to the wound edge. This reorientation of the two organelles in cells at the wound edge was evident within minutes after wounding and persisted as cell extension subsequently occurred into the wound. These results suggest that both the Golgi apparatus and the microtubule-organizing center may participate in directing cell movement. The possible mechanisms involved are discussed in the light of previous hypotheses and experimental evidence concerning cell motility.
TL;DR: The findings are that changes in stress and motion significantly altered the tissue properties as well as mass in the case of ligaments and digital extensor tendons, Whereas, no significant changes in properties and mass were detected for the digital flexor tendons.
TL;DR: Model-building studies indicate that this structure is important in DNA binding, and it is suggested that it may be a common feature of many DNA-binding proteins.
Abstract: The amino acid sequences of the repressor and cro proteins of phages lambda, 434 and P22 are homologous, especially in a region in which repressor and lambda cro have a similar alpha-helix-turn-alpha-helix secondary structure Model-building studies indicate that this structure is important in DNA binding, and we suggest it may be a common feature of many DNa-binding proteins
TL;DR: Findings indicate that early protected passive mobilization augments the physiologic processes that determine the strength and excursion of repaired flexor tendons.
Abstract: The response of healing canine flexor tendons to motion was investigated using protected passive mobilization techniques. Early motion, delayed motion, and immobilization groups were compared over a 12-week period,for their strength and excursion characteristics. Tendons which were mobilized early showed progressively greater ultimate load and linear slope values at each time interval tested. The ultimate load of the immediately mobilized tendons, those tested at 3 weeks, was twice as great, and the linear slope values were almost three times greater than the immobilized repairs at 3 weeks. Similar differences were noted at each time interval through 12 weeks. The differences in angular rotation of the distal interphalangeal joint.following the application ql a small load were also significant. At 12 weeks, the angular rotation of the tendons of the immobilization group averaged only 19% ± 2%r of their intact contralateral controls. The delayed mobilization tendons produced values (?f'67% ± 8%, and the immediate mobilization tendons produced 95% ± 10% of the control joint motion. These findings indicate that earls protected passive mobilization augments the physiologic processes that determine the strength and excursion of repaired flexor tendons.
TL;DR: It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain.
Abstract: • As part of a six-center clinical trial of the effectiveness of continuousvnocturnal oxygen in the management of hypoxemic chronic obstructive pulmonary disease (COPD), we performed detailed neuropsychologic assessments of these patients prior to their beginning treatment. The 203 patients (age, 65 years; Pao2, 51 mm Hg; forced expiratory volume in 1 s, 0.74 L) performed significantly worse than controls on virtually all neuropsychologic tests. Moderate to severe test impairment suggestive of cerebral dysfunction was found in 42% of the patients, as compared with 14% of controls. Higher cognitive functions (abstracting ability, complex perceptual-motor integration) were most severely affected, although half the patients also showed decrements in motor speed, strength, and coordination. Low-order significant inverse correlations were found between neuropsychologic impairment and Pao2, resting arterial oxygen saturation and hemoglobin levels and maximum work. It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain. (Arch Intern Med1982;142:1470-1476)
TL;DR: Since, like other plasma proteins, LDL undergoes glucosylation in diabetes, its turnover and sites of catabolism may differ from normal and this may be relevant to the accelerated atherosclerosis of diabetes.
Abstract: Human low-density lipoprotein (LDL) was glucosylated by incubation in vitro with glucose (20-80 mM) with or without addition of cyanoborohydride. The incorporation of covalently bound glucose was linear over time, and amino acid analysis showed the presence of glucosyllysine residues. The glucosylated LDL (glc LDL) moved more rapidly than normal LDL on agarose electrophoresis. The rate of degradation of 125I-labeled glucosylated LDL (glc LDL) by cultured human fibroblasts was reduced compared with that of native I-LDL, the difference increasing with extent of glucosylation. Effects were seen with blockage of as few as 6-15% of the LDL lysine residues; high-affinity degradation was completely lost when one-third of the lysine residues were blocked. Conjugation of LDL with glucose-6-phosphate also blocked high-affinity uptake and degradation. Whereas native LDL uptake inhibited the activity of beta-hydroxy-beta-methylglutaryl coenzyme A reductase and stimulated acyl coenzyme A:cholesterol acyltransferase activity, glc LDL had no effects on these enzymes. The fractional catabolic rate of glc LDL in guinea pigs was reduced. Degradation of glc LDL by mouse peritoneal macrophages was not significantly faster than that of native LDL. Finally, the presence of glc LDL in human plasma was demonstrated. Preliminary data show that 1.3% of lysine residues in normal LDL and 2-5.3% of lysines in diabetic LDL were glucosylated. Since, like other plasma proteins, LDL undergoes glucosylation in diabetes, its turnover and sites of catabolism may differ from normal and this may be relevant to the accelerated atherosclerosis of diabetes.
TL;DR: In this review, only complete disappearance of the gallstones is accepted as a successful result, since reduction of size during treatment does not guarantee that continued treatment will result in complete dissolution.
Abstract: Effectiveness Dissolution of Gallstones. In almost every report of treatment of patients with cholesterol gallstones with UDCA, the calculation of the success rate is based on the sum of the complete and partial dissolutions, in this review~ only complete disappearance of the gallstones is accepted as a successful result, since reduction of size during treatment does not guarantee that continued treatment will result in complete dissolution. Data from publications which do not distinguish between partial and complete dissolution in presenting the rate of successful treatment are therefore not included in the tabulations. Furthermore, some of the authors display their data in a way which makes it impossible to understand their results. This is attributable in no small measure to changes of dosage during the trial instead of continuing with a given dose in a given patient. Where the dose is stated in mg/kg/day, it was certainly not prescribed that way. The investigators prescribed the number of tablets or capsules to be taken daily, then calculated the dose on a weight basis. The smallest number of patients in any series was 12 (140), the largest 106 (145), the latter a multicenter study. The total number of patients entered in all series (Table 18) was 852, of whom 128 (15%) dropped out. Drop-outs are defined in this review as
TL;DR: The results indicate that the hippocampus, amygdala, or both, but not the temporal stem, are involved in memory in the monkey and suggest that a rapprochement between the findings for the human and the nonhuman primate may be close at hand.
Abstract: Using a task known to be sensitive to human amnesia, we have evaluated two current hypotheses about which brain regions must be damaged to produce the disorder. Monkeys with bilateral transections of the white matter of the temporal stem were unimpaired, but monkeys with conjoint amygdala-hippocampal lesions exhibited a severe memory deficit. The results indicate that the hippocampus, amygdala, or both, but not the temporal stem, are involved in memory in the monkey and suggest that a rapprochement between the findings for the human and the nonhuman primate may be close at hand.
TL;DR: In this article, a diagnostic test is formulated by taking the current model as the null hypothesis and a particular form of misspecification as the alternative, and the test is derived in two theorems corresponding to different models.
TL;DR: The viral glycoprotein GP-1 likely contains both the attachment and fusion activities of mouse hepatitis virus-4, as well as three viral polypeptide specificities characterized by indirect immunofluorescence and immune precipitation.
TL;DR: In patients without complicating factors in the electrocardiogram and with a single infarct, the electro Cardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarCT size.
Abstract: This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.
TL;DR: The purification of p97 by affinity chromatography with monoclonal antibody, followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and determination of the N-terminal amino acid sequence using a new, highly sensitive protein sequencer found the sequence to be homologous to the N -terminal sequences of transferrin and lactotransferrin.
Abstract: p97 is a 97,000-molecular weight (MW) cell-surface glyco-protein, which is present in most human melanomas but in only trace amounts in normal tissues1–4. We describe here the purification of p97 by affinity chromatography with monoclonal antibody, followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and determination of the N-terminal amino acid sequence using a new, highly sensitive protein sequencer5. The sequence was found to be homologous to the N-terminal sequences of transferrin and lactotransferrin. This structural homology was confirmed by the observation that antiserum to denatured p97 cross-reacted with denatured transferrin and lactotransferrin. We have also demonstrated that p97 is functionally related to transferrin and lactotransferrin in that it binds iron. This is one of the first reports of the amino acid sequence of a human tumour-associated cell-surface antigen and one of the few cases in which insight has been obtained into its function.
TL;DR: In this paper, a simple physical model is presented to explain the oscillatory oxidation of CO over Pt, Pd and Ir catalysts, where the slow oxidation and reduction of the metal surface layer induces transitions between these two branches of a Langmuir-Hinshelwood reaction mechanism.
TL;DR: Free-oscillation data reveal heterogeneity in the Earth's mantle whose geographical pattern is dominated by spherical harmonics of angular degree two and correlates well with the hydrostatically referenced geoid.
Abstract: Free-oscillation data reveal heterogeneity in the Earth's mantle whose geographical pattern is dominated by spherical harmonics of angular degree two and correlates well with the hydrostatically referenced geoid. The heterogeneity can be modelled as localized in the transition zone (420–670 km depth) and may be related to a large-scale component of mantle convection.
TL;DR: A cDNA clone of the mRNA encoding the glycoprotein (G) of vesicular stomatitis virus was inserted into plasmid vectors under the control of either the SV40 early promoter (pSV2G) or the SV 40 late promoter ( pSVGL).