Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rationalization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed2004

Rational design of potent and selective VLA-4 inhibitors and their utility in the treatment of asthma.

Asthma, a chronic inflammatory disease of the airways, is a significant burden on our healthcare system. There is high unmet need for treatments directed towards the underlying causes of the disease. The cell surface integrin VLA-4 (very late antigen-4; alpha4beta1; CD49d/CD29) plays an important role in the trafficking of white blood cells to sites of inflammation and represents an exciting target for the development of novel anti-inflammatory drugs for the treatment of asthma. Here, we review our efforts to use rational design to identify potent, selective inhibitors of VLA-4. We describe the discovery of a series of potent VLA-4 inhibitors through the addition of a novel N-terminal organic cap to a tetrapeptide VLA-4 binding motif 4-((N'-2-methylphenyl)uriedo)phenylacetyl-Leu-Asp-Val-Pro ; Kd = 70 pM), and rationalize their structure-activity relationships using 3D-QSAR. Also, we show our rational peptidomimetic design strategy using "template hopping" from the gpIIb/IIIa integrin antagonist field, and also a novel virtual screening strategy. Two series have been developed, one that has high selectivity for the activated over the non-activated state of the receptor, and the other which is non-selective inhibiting both activated and non-activated VLA-4. Both series are highly selective for VLA-4 versus against other integrin family members. These inhibitors show promise in the treatment of asthma, based upon efficacy in a sheep model of asthma, where they inhibit both the early and late-phase responses to asthma and also block hypersensitivity.

Amides↗
PubMed1998

Psychiatric hospitals and instrumental rationality.

Therapists in psychiatric hospitals often overuse a model borrowed from natural science, with the patient becoming an object to be examined, assessed, and altered, and underuse an interpretive psychotherapeutic approach, or misuse it to control patients. And while expressing an interest in the meaning of what patients say, they exclude most of the traditional sources of meaning, in ethics, religion, literature, art, and political thought. The author argues that therapists do these things for two ideological reasons: to maintain their position in the authoritarian structure of the hospital and to maintain the hospital as an agent of class domination. Along with other groups, therapists bring instrumental rationality, such as that of natural science, to bear on political, cultural, and personal questions for which this type of rationality is often destructive. In the long run, political participation and social integration decrease, culture traditions provide less meaning, and personality formation is disrupted. Thus the end result of the overuse of instrumental rationality is not only domination by one class of others, but a decrease in the stability of the society as a whole. Hospital therapists participate in these trends, but they could do otherwise, by working to create a more democratic form of therapy.

Culture↗
PubMed2004

Composition and aroma compounds of Ragusano cheese: native pasture and total mixed rations.

Raw milk from 13 cows fed TMR supplemented with native pasture and from 13 cows fed only TMR on one farm was collected separately 4 times with an interval of 15 d between collections. Two blocks (14 kg each) of cheese were made from each milk. The objective was to determine the influence of consumption of native plants in Sicilian pastures on the aroma compounds present in Ragusano cheese. Milk from cows that consumed native pasture plants produced cheeses with more odor-active compounds. In 4-mo-old cheese made from milk of pasture-fed cows, 27 odor-active compounds were identified, whereas only 13 were detected in cheese made from milk of total mixed ration-fed cows. The pasture cheeses were much more rich in odor-active aldehyde, ester, and terpenoid compounds than cheeses from cows fed only total mixed ration. A total of 8 unique aroma-active compounds (i.e., not reported in other cheeses evaluated by gas chromatography olfactory) were detected in Ragusano cheese made from milk from cows consuming native Sicilian pasture plants. These compounds were 2 aldehydes ([E,E]-2,4-octadienal and dodecanal), 2 esters (geranyl acetate and [E]-methyl jasmonate), 1 sulfur compound (methionol), and 3 terpenoid compounds (1-carvone, L(-) carvone, and citronellol). Geranyl acetate and (E)-methyl jasmonate were particularly interesting because these compounds are released from fresh plants as they are being damaged and are part of a possible plant defense mechanism against damage from insects. Most of the odor-active compounds that were unique in Ragusano cheese from pasture-fed cows appeared to be compounds created by oxidation processes in the plants that may have occurred during foraging and ingestion by the cow. Some odor-active compounds were consistently present in pasture cheeses that were not detected in the total mixed ration cheeses or in the 14 species of pasture plants analyzed. Either these compounds were present in other plants not analyzed, created in the rumen or in cheese after the pasture-plant material had been consumed, or the compounds were lost in the method of sample extraction used for the plant analysis (i.e., steam distillation) versus the solid-phase microextraction method used for the cheeses. This research has demonstrated clearly that some unique odor-active compounds found in pasture plants can be transferred to the cheese.

Animal Feed↗
PubMed2004

Effects of feeding rations with genetically modified whole cottonseed to lactating Holstein cows.

Two experiments were conducted to evaluate dry matter intake (DMI), milk yield, and milk composition from feeding rations that contained different sources of genetically modified whole cottonseed to Argentinean Holstein dairy cows. Twenty-four lactating multiparous Argentinean Holstein dairy cows were used in 2 experiments with a replicated 4 x 4 Latin square design, with cows averaging 565 kg body weight and 53 d in milk at the beginning of the experiments. Treatments in Experiment 1 were: Bollgard cotton containing the cry1Ac gene, Bollgard II cotton containing cry1Ac and cry2Ab genes, Roundup Ready cotton containing the cp4 epsps gene, and a control nongenetically modified but genetically similar cottonseed. In Experiment 2, two commercial sources, a parental control line, and the transgenic cotton containing both cry1Ac and cp4 epsps genes were used as treatments. All cows received the same total mixed ration but with different whole cottonseed sources. Cottonseed was included to provide 2.50 kg per cow daily (dry matter [DM] basis) or about 10% of the total diet DM. The ingredient composition of the total mixed ration was 32% alfalfa hay, 28% corn silage, 22% corn grain, 17% soybean meal, and 2% minerals and vitamins. In addition, genomic DNA was extracted from a subset of milk samples and analyzed by polymerase chain reaction followed by Southern blot hybridization for small fragments of the cry1Ac transgene and an endogenous cotton gene, acp1. No sample was positive for transgenic or plant DNA fragments at the limits of detection for the assays following detailed data evaluation criteria. The DMI, milk yield, milk composition, body weight, and body condition score did not differ among treatments. Cottonseed from genetically modified varieties used in these studies yielded similar performance in lactating dairy cows when compared to non-transgenic control and reference cottonseed.

Animal Feed↗
PubMed1976

Effects of citrus pulp in high urea rations for steers.

Effects of pelleted and conventional citrus pulp as a replacement for corn, with soybean meal added to keep protein comparable, were tested in rations with 5% urea and 33.33% sugarcane bagasse for fistulated steers. Thus, all rations were low in readily fermented carbohydrates other than those of corn or citrus pulp. Evaluation criteria were concentrations of urea in blood and of pH, ammonia, and volatile fatty acids of rumen fluid. Citrus pulp for diets 1, 2, 3, and 4 was 0, 19, 38, or 55%. Rumen fluid and blood were sampled 1 h before and 2, 4, 7, and 12 h after feed was placed directly into the rumen. No differences between pelleted and conventional pulp or among time trends were significant except that for both forms rumen ammonia was lower with the two highest percents of citrus pulp. Addition of citrus pulp at 0, 19, 38, or 55% of the ration reduced rumen pH (6.85, 6.65, 6.61, 6.51). Blood urea and rumen ammonia decreased in steers fed 19, 38, or 55% pulp; thus, the acetic to propionic ratio was higher. Butyric acid changed only in the time trend. Total volatile fatty acid concentrations were higher at 19, 38, and 55% than at 0% pulp. They were higher at 38 and 55 than at 19%.

Ammonia↗
PubMed1985

Nutritive value of potato processing wastes in total mixed rations for dairy cattle.

The nutritive value of wet potato processing waste for dairy cattle was determined in two experiments. In Experiment 1, rations contained, on a dry matter basis, 0, 10, 15, and 20% potato waste and were substituted for high moisture corn in diets for 32 lactating Holstein cows for 12 wk. Substituting potato waste for corn did not significantly affect milk yield, milk composition, milk production persistency, or dry matter intake. Cows fed 20% potato waste tended to decrease in milk fat percent and to shift molar proportions of rumen volatile fatty acids toward a decrease in acetate: propionate ratio. In Experiment 2, six steers were used in a 3 X 3 Latin square design to test digestibility and nitrogen utilization of potato waste substituted for high moisture corn at 0, 10, and 20% of the ration dry matter. A second group of four steers with rumen fistulas were used in a 4 X 4 Latin square to test rumen fermentation parameters. Diets contained 0, 10, 20, and 30% potato wastes and were similar to Experiment 1. Potato waste did not significantly affect digestibility of crude protein or dry matter, but at 20% substitution digestibility of acid detergent fiber decreased. Rumen ammonia, acetate, acetate to propionate ratios, and total volatile fatty acids were lower at high intakes of potato waste and pH was increased. The shift in rumen fermentation when large amounts of potatoes were fed explains the depressed butter fat on these rations.

Animal Feed↗
PubMed1985

Effects of adding beta-carotene to rations of lactating cows consuming different forages.

Thirty-six Holstein cows fed a corn silage-based ration and 34 fed an alfalfa-grass silage-based ration were assigned according to calving date to receive either 300 mg/head per day of synthetic beta-carotene in a gelatin capsule or an empty gelatin capsule daily for the first 100 days postpartum. Supplemental vitamin A was provided at 3919 IU/kg of ration dry matter. Cervix diameters for cows supplemented with beta-carotene were smaller at 21 days and 28 days postpartum. Days from parturition to first observed estrus were less when beta-carotene was added and less when corn silage was fed. Means of other reproductive traits were more favorable for cows treated with beta-carotene (fewer services per conception and shorter intervals between parturition and conception). Milk progesterone at 21 and 28 days postpartum was not affected by either roughage or beta-carotene treatment. Milk from cows receiving alfalfa-grass silage contained lower somatic cell concentrations than that produced by cows fed corn silage. Milk somatic cell concentrations were lower in both roughage treatment groups for cows supplemented with beta-carotene. No effects of roughage or beta-carotene on milk production or milk fat percentages were significant.

Animal Feed↗
PubMed1989

Improved energy prediction equations for dairy cattle rations.

The objective was to develop equations that would accurately predict energy contents of rations commonly fed to milking cows and that were simple to apply. Six published equations that predicted TDN from ration content of crude fiber or ADF or predicted digestible energy, metabolize energy, or NE(1) from ration ADF content were modified to remove bias caused by dietary fiber contents. The modified equation that predicted metabolizable energy from ADF was tested for accuracy using data from several feeding trials in which DM intakes and dietary ADF contents were known. Dietary metabolizable energy content calculated by the equation was multiplied by DM consumed to obtain metabolizable energy intake. Requirement of dietary metabolizable energy was calculated using factors for maintenance, milk produced, and BW changes from 1988 NRC feeding standard. Concurrence values (energy intake/energy required) from feeding trials were calculated and served as the criterion of equation accuracy. Several trials resulted in concurrence values approximating 1.0, indicating that the equation to predict dietary metabolizable content was accurate. However, values for individual trials ranged from .84 to 1.21. Concurrence values that deviated considerably from 1.0 occurred most frequently in trials in which animals experienced negative or large changes in BW. It appeared that errors may have occurred in calculating energy requirements when BW changes were negative or large. It was concluded that the modification improved the original equation and it probably was accurate. The other modified equations would be expected to be equally accurate.

Animal Feed↗
PubMed1983

Phosphorus. 1. Effect of breed and strain on utilization of suboptimal levels of phosphorus in the ration.

Single Comb White Leghorn cockerel chickens were able to utilize suboptimal levels of phosphorus in the ration more efficiently than broiler cockerel chickens as measured by growth, livability, and bone calcification. The superiority of the Leghorn-type over the broiler-type in utilizing suboptimal levels of phosphorus was accentuated by high levels of calcium in the ration. Among broiler strains the Athens Canadian Randombred cockerel chicken utilized suboptimal levels of phosphorus more efficiently than the two commercial strains tested. The Single Comb White Leghorn chickens showed higher retention values for calcium, phosphorus, and phytin phosphorus than the broiler strain. High calcium levels in the ration caused a much lower retention of phytin phosphorus by both Single Comb White Leghorn and broiler chickens.

Animals↗
PubMed1985

The effect of pelleting the layer ration on egg size in early-housed brown-egg-type layers.

Harco Sex-Link pullets (n = 360) were reared in cages and given a 15% protein grower ration. At 17 weeks of age, half the birds were transferred to laying cages and the photoperiod was increased to 13 hr for the first week and to 15 hr thereafter. The remaining birds were continued in the growing facility on 8 hr of light until 19 weeks when lights were increased to 13 hr daily. These birds were transferred to the laying cages at 20 weeks of age where they received 15 hr of light. At 2% production, all birds were fed a 17% protein layer diet in either a mash or pelleted form. Neither egg production nor feed efficiency was affected by age at housing or the physical form of the ration. Early-lighted pullets produced a greater percentage of small and medium-sized eggs. Egg size distribution was not affected by the physical form of the ration

Animal Feed↗
PubMed1982

Effects of ration, season and animal handling on composition of bison and cattle blood.

Composition of ration and season of sampling markedly affected the composition of blood in six tamed bison (Bison bison) steers and eight Hereford cattle (Bos taurus) steers. Observed values extended reported ranges for albumin, phosphorus and blood urea nitrogen (BUN) in bison serum. There were several differences between species in blood composition. In particular, erythrocytic and BUN values were higher in bison than in cattle. Overall mean values for bison and cattle receiving experimental rations were, respectively: BUN, 17.1 mg/dl and 14.1 mg/dl; hemoglobin, 17.8 g/dl and 13.3 g/dl; packed cell volume (PCV), 47.6% and 35.6%; red blood cells, 9.3 x 10(6)/mm3 and 8.2 x 10(6)/mm3; mean corpuscular volume (MCV), 51.3 mean 3; mean corpuscular hemoglobin, 18.9 pg and 16.1 pg. The significant changes in blood composition associated with changes in ration composition support the use of blood composition as an index of nutritional status. There were no sex-specific differences in blood of 20 bison from Elk Island National Park and 34 bison from Wood Buffalo National Park, Alberta. Alkaline phosphatase (ALP) level was higher in juvenile than in adult bison. Impoundment of wild bison for 24 hr was accompanied by a decrease in BUN and an increase in PCV. Wild bison that were killed during handling had significantly higher blood levels of ALP, glutamate oxaloacetate transaminase, MCV and phosphorus.

Animal Feed↗
PubMed2000

Plasticity and steric strain in a parallel beta-helix: rational mutations in the P22 tailspike protein.

By means of genetic screens, a great number of mutations that affect the folding and stability of the tailspike protein from Salmonella phage P22 have been identified. Temperature-sensitive folding (tsf) mutations decrease folding yields at high temperature, but hardly affect thermal stability of the native trimeric structure when assembled at low temperature. Global suppressor (su) mutations mitigate this phenotype. Virtually all of these mutations are located in the central domain of tailspike, a large parallel beta-helix. We modified tailspike by rational single amino acid replacements at three sites in order to investigate the influence of mutations of two types: (1) mutations expected to cause a tsf phenotype by increasing the side-chain volume of a core residue, and (2) mutations in a similar structural context as two of the four known su mutations, which have been suggested to stabilize folding intermediates and the native structure by the release of backbone strain, an effect well known for residues that are primarily evolved for function and not for stability or folding of the protein. Analysis of folding yields, refolding kinetics and thermal denaturation kinetics in vitro show that the tsf phenotype can indeed be produced rationally by increasing the volume of side chains in the beta-helix core. The high-resolution crystal structure of mutant T326F proves that structural rearrangements only take place in the remarkably plastic lumen of the beta-helix, leaving the arrangement of the hydrogen-bonded backbone and thus the surface of the protein unaffected. This supports the notion that changes in the stability of an intermediate, in which the beta-helix domain is largely formed, are the essential mechanism by which tsf mutations affect tailspike folding. A rational design of su mutants, on the other hand, appears to be more difficult. The exchange of two residues in the active site expected to lead to a drastic release of steric strain neither enhanced the folding properties nor the stability of tailspike. Apparently, side-chain interactions in these cases overcompensate for backbone strain, illustrating the extreme optimization of the tailspike protein for conformational stability. The result exemplifies the view arising from the statistical analysis of the distribution of backbone dihedral angles in known three-dimensional protein structures that the adoption of straight phi/psi angles other than the most favorable ones is often caused by side-chain interactions. Proteins 2000;39:89-101.

Bacteriophage P22↗
PubMed1999

[Lead and cadmium content in daily food rations of children and adolescents from copper basin of the Legnica region].

Environmental pollution still remains a serious problem in some heavily industrialized regions of Poland. Among various xenobiotics prevalent in human environment heavy metals such as lead and cadmium are considered as most harmful to living systems. The main source of these metals for humans is food and water, therefore increased dietary lead and cadmium intake may cause functional disturbances of various body systems, especially in young developing organisms. The objective of this study was to evaluate the lead and cadmium content in daily food rations served at two selected Children Guardian Centres (CGC) located in the region of Copper Basin Legnica (Głogów and Polkowice), during winter and spring seasons in 1996. The lead and cadmium content was determined after dry mineralization of samples by the FAAS method with deuterium BC. It was found that the lead and cadmium content in daily food rations exceeded the PTWI limits for children and adolescents in both CGC. Moreover, seasonal and regional variations of the lead and cadmium content in daily meals were observed. Generally, higher levels of lead in food rations were determined in the winter season whereas the cadmium content was higher in the CGC in Głogów in comparison to Polkowice.

Adolescent↗
PubMed2001

Diet restriction in rat toxicity studies: automated gravimetric dispensing equipment for allocating daily rations of powdered rodent diet into pouches and 7-day feeders.

Survival of ad libitum-fed rats has declined in the 2-year carcinogenicity bioassay. Restriction of the number of calories, without compromise of the overall nutrition offered to animals including rats, results in increased lifespan of animals. Diet restriction in rats is best achieved through offering of rations of feed daily instead of weekly, as is routinely done in ad libitum studies. The objective of this project was to develop an accurate and precise method of dispensing daily rations of feed. A gravimetric vibratory-type dispenser was used to dispense target weights of 15 and 20 g of powdered certified rodent diet into either labeled pouches or seven-well carousel feeders. The tolerance of the dispenser was the target weight +/- 3%. The amount of food offered to the diet-restricted rats was approximately 25% lower than that consumed by rats offered diet ad libitum. After 2 years, male rats offered 20 g and female rats offered 15 g of powdered rodent diet daily had remarkably lower body weights than did animals offered the diet ad libitum. Generally, the rats ate the entire ration of food offered to them each day. Survival of the diet-restricted rats was 70% to 82% at the end of a 2-year study. This investigation demonstrates that modest reduction of food intake, resulting in increased survival of Sprague Dawley rats in 2-year carcinogenicity bioassays, can be achieved reliably and efficiently through use of an accurate and precise automated method of dispensing powdered diet for use in multiple rat studies. In addition, this method of food dispensing provides a practical way to administer test compound in the diet under the conditions of diet restriction.

Animal Feed↗
PubMed2001

Dietary intakes of Mg, Ca and P with whole-day food rations from Cracovie, Lodz, Olsztyn and Poznan, Poland.

Magnesium, calcium and phosphorus have been determined in whole-day food rations collected during three consecutive days in winters of 1993/4, 1995 and 1996 in hospital canteens in Krakow, Lodz, Olsztyn and Poznan, Poland. Portions of food for one person were collected. In 1998 whole-day food rations of seven students (five consecutive days) and, in 1999, of eight adults (three consecutive days) were also prepared for Mg, Ca and P determination. Mg and Ca were determined by ASA and P by colorimetric method. The diets collected at hospital canteens were deficient in magnesium but not in calcium. Duplicate diets did not supply enough magnesium and calcium. All the whole-day food rations contained 2-4-fold excess of phosphorus. Such a composition of macroelements in food can pose a threat to human health.

Adult↗
PubMed2001

[Sodium chloride in food rations and dinners in mass catering institutions].

The sodium chloride content in meals given by mass catering institution in all over country in 1988-1998 years was estimated. This study included daily food rations from 183 mass catering institution as hospitals, sanatoriums for both children and adults, boarding schools, infant schools and social welfare homes. We assessed also school dinners from 422 randomized selected schools and dinners from 55 internal and 56 surgical departments of provincial and regional hospitals in Poland. The mass of each meal was evaluated and sodium chloride content by Mohr's method was assessed. In most cases the salt content by 100 g of meal of 1000 kcal was calculated. The dinners and daily food rations analyze showed that sodium chloride content in meals was much higher than value recommended by World Health Organization (WHO). Salt amount in daily food rations of both children and adults was above 16 g. This value didn't include salt added to meals by boarders. School dinners provided about 7-10 g of salt. The average sodium chloride content in hospital dinners was about 16-20 g. In each studied group the NaCl content per 100 g of meal was similarly high and was 0.7-0.9 g. The results of this study show that meals given by mass catering institutions can increase risk of hypertension, strokes and gastric cancers because of high sodium chloride content.

Adult↗
PubMed1975

Preliminary study on using fermented skim milk in poultry rations.

80 (4 X 20) four-month-old cockerels were fed the following rations for six weeks: Group 1 = corn and green berseem, group 2 = corn, green berseem, and skim milk, groups 3 and 4 = corn, green berseem, and fermented skim milk. Feeding was ad libitum in groups 1 to 3, and 80% of the group 3 standard in group 4. The live weight increased in all groups during the experimental period. In group 4 it was higher at the end of the experiment than that of groups 1 to 3. But the difference was statistically not significant. The amount of starch units required per unit of live weight increase during the experimental period was 9.76 (group 1) 11.00 (group 2), 10.72 (group 3), and 9.66 (group 4). The visceral fat weights were higher in groups 2 and 3 (not significant). 40 (2 x 20) four-week-old ducklings were fed a commercial ration (group 5) or 65% of this ration supplemented with 35 ml of fermented skim milk (group 6). There were no significant differences in the live weight gains. The amount of starch units required per unit of live weight increase was 2.89 (group 5) and 3.61 (group 6).

Animal Feed↗
PubMed1987

[Internal migration in developing countries: rationality of rural-urban migration].

"In many developing countries there is a positive and nondecreasing rural-urban net migration. As a rule, making migration decisions jointly is advantageous for individual potential migrants and their families. Rationality of migration decisions depends on the specific character of the constituents of the basic decision model. In most cases, individual or family rationality of migration does not coincide with collective rationality. Trying to bring the two together requires trying to improve the coordinative function of main economic variables and trying to improve the decision makers' information." (SUMMARY IN ENG)

Behavior↗