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A 28-kDa cerebral neuropeptide from Manduca sexta: relationship to the insect prothoracicotropic hormone.

1. A 28-kDa peptide from the brain of the tobacco hornworm, Manduca sexta, was purified via HPLC. The peptide copurified with the insect neurohormone, prothoracicotropic hormone (PTTH), through two HPLC columns. 2. Immunocytochemistry using polyclonal antibodies against the 28-kDa peptide revealed that the peptide was produced in the same protocerebral neurons that produce PTTH. Western blot analysis demonstrated that the 28-kDa peptide and big PTTH are different molecules. 3. A PTTH in vitro bioassay indicated that despite having chromatographic properties similar to those of big PTTH and being produced by the same neurons, the 28-kDa peptide did not have PTTH activity. 4. Amino acid sequence analysis yielded a 27 N-terminal amino acid sequence that had no similarity with known peptides. 5. Immunocytochemical studies revealed that the 28-kDa peptide is present as early as 30% embryonic development and is absent by adult eclosion. This is in contrast to big PTTH, which is expressed throughout the Manduca life cycle. 6. These data suggest that the 28-kDa peptide is another secretory phenotype of the lateral neurosecretory cell group III (L-NSC III) which may have functions distinct from those for big PTTH or may act synergistically with big PTTH.

Animals↗

Using urbanization profiles to assess screening performance.

The large Dutch data sets acquired as a result of population-based cervical smear screening programs can be further exploited to obtain an urbanization-weighted score to gain insight into the quality of the performance of the individual cytology laboratories. Based on the first four digits of the postal code of the screenees, the data are stratified according to urbanization. Urb 1 corresponds to (semi)rural, which includes villages and small townships with less than 20,000 inhabitants; Urb 2, to towns with between 20,000 and 250,000 inhabitants; and Urb 3, to big cities, in this case, The Hague. From the postal code data of the screenees, the urbanization profiles of the laboratories can be calculated. The urbanization degree proved to have a substantial effect on the cytologic scores in the four laboratories. The number of expected, urbanization-weighted patient cases is calculated. Accordingly, the laboratories could be compared with respect to performance. We conclude that laboratories in our screening program were quite similar in performance for the cytologic diagnosis leading to referral to the hospital, with little difference between the actual and the expected, urbanization-weighted number of cases. It is evident that the equation for calculating the expected scores for S5-S9 is relevant for control of quality of care provided by laboratories and regions, but also for the quality of these assessments.

Female↗

Detection of cyclophosphamide-induced mutations at the Hprt but not the lacI locus in splenic lymphocytes of exposed mice.

The relative sensitivities and specificities of the endogenous Hprt gene and the lacI transgene as mutational targets were evaluated in splenic lymphocytes from male standard B6C3F1 mice (only Hprt assayed) and from lacI transgenic B6C3F1 mice treated at 6-7 weeks- of-age with the indirect-acting agent, cyclophosphamide (CP). To define the effects of the time elapsed since CP treatment on Hprt mutant frequencies (Mfs), nontransgenic mice were given single i.p. injections of 25 mg CP/kg or vehicle (PBS) alone and then necropsied 2, 4, 6, 8, or 10 weeks after treatment. Peak Mfs were found at 6 weeks postexposure, with mean Mf values ranging from 2.27 to 3.27 x 10(-5) using two different lots of CP in standard packaging (compared with mean control Mf values of 0.14 to 0.26 x 10(-5) in various experiments). To determine the dose response for Hprt Mfs, nontransgenic mice were given single doses of 0, 12.5, 25, 50, or 100 mg CP/kg and necropsied 4 weeks postexposure. These treatments produced a supralinear dose response curve for CP-induced Hprt Mfs. Based on these experiments, CP mutagenicities at Hprt and lacI were compared in transgenic mice treated with 0, 25, or 100 mg CP/kg (using another lot of CP in ISOPAC((R)) bottles; Sigma) and necropsied 6 weeks later. There was a significant increase in Hprt Mfs in treated transgenic mice (100 mg CP/kg: 0.75 +/- 0.09 x 10(-5); 25 mg CP/kg: 0.39 +/- 0.05 x 10(-5)) versus controls (0.10 +/- 0.01 x 10(-5)); however, the Mfs in lacI of lymphocytes from the same CP-treated animals were not significantly different from controls (100 mg CP/kg: 9.4 +/- 1.1 x 10(-5); 25 mg CP/kg: 6.7 +/- 0. 8 x 10(-5); control: 7.7 +/- 0.7 x 10(-5)). Hprt mutational spectra data in CP-treated transgenic and nontransgenic mice were different from those of control mice, whereas the spectra of mutations in lacI of lymphocytes from Big Blue((R)) transgenic mice were not significantly changed after CP treatment. These data indicate that, under these treatment conditions, CP-induced mutations in splenic lymphocytes were detectable in the Hprt gene but not the lacI transgene of this nontarget tissue for CP-induced cancer.

Animals↗

Employer health insurance and local labor market conditions.

Theory suggests that an employer's decisions about the amount of health insurance included in the compensation package may be influenced by the practices of other employers in the market. We test the role of local market conditions on decisions of small employers to offer insurance and their dollar contribution to premiums using data from two large national surveys of employers. These employers are more likely to offer insurance and to make greater contributions in communities with tighter labor markets, less concentrated labor purchasers, greater union penetration, and a greater share of workers in big business and a small share in regulated industries. However, our data do not support the notion that marginal tax rates affect employers' offer decision or contributions.

Adult↗

[Relation between osmo- and volume-regulation in mammals with different renal capacities for osmotic concentration of urine].

The effect of increase in osmolarity of the blood on osmotic and volume controls has been investigated in Wistar rats, Brattleboro rats and big gerbil by means of i. v. administration of polyethyleneglycol-400 (PEG). PEG injections (0.17 ml/100 g) increased osmolarity of the blood by 3-4% in rodents of the species under study; concentrations of sodium, potassium and urea changed unequally. Significant differences were revealed when comparing the work of kidneys: the diuresis elevated by 55.7 times in Wistar rats and their renal sodium and urea excretions exceeded more than two-fold the level of that at the peak of the diuresis in big gerbil and Brattleboro rat. PEG excretion rate was significantly lower in latters than in Wistar rats. The data obtained suggest that the volume regulation is predominant under osmotic control in Brattleboro rat and in big gerbil.

Animals↗

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 2. Semipredictive or semiempirical models.

The solubility of stearic acid, ranitidine hydrochloride, and stavudine were predicted in selected organic solvents. The experimental solubility data of stearic acid and ranitidine hydrochloride were reported in previous work of the authors and stavudine's solubility was measured in this work. Equilibrium aqueous solubility of crystalline stauvudine was determined at controlled temperatures by stirring and filtration, with spectrophotometric quantification. The new model developed in Part 11 of this communication was modified as a semipredictive model with two adjustable parameters. Predicting the solubility data with the NRTL model using just one experimental point resulted in a big error while the modified new model and the UNIQUAC model showed much smaller errors. A new method was proposed in this work for predicting the solubility data of all polymorphs of a given compound using the experimental solubility data of one of the polymorphs of the same chemical compound. Although in general, the UNIQUAC model predictions were marginally superior, the new model is simpler and does not require the molecular parameters such as Van der Waals area and volume. The solubility prediction in a mixture of solvents using the NRTL and UNIQUAC models was also discussed.

2-Propanol↗

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗