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 829 records · Page 46Linked to original sources
PubMed2006

Quasicrystalline and rational approximant wave patterns in hydrodynamic and quantum nested wells.

The eigenfunctions of nested wells with an incommensurate boundary geometry, in both the hydrodynamic shallow water regime and quantum cases, are systematically and exhaustively studied in this Letter. The boundary arrangement of the nested wells consists of polygonal ones, square or hexagonal, with a concentric immersed, similar but rotated, well or plateau. A rich taxonomy of wave patterns, such as quasicrystalline states, their crystalline rational approximants, and some other exotic but well known tilings, is found in these mimicked experiments. To the best of our knowledge, these hydrodynamic rational approximants are presented here for the first time in a hydrodynamic-quantum framework. The corresponding statistical nature of the energy level spacing distribution reflects this taxonomy by changing the spectral types.

Journal Article↗
PubMed2002

Self-interaction chromatography: a novel screening method for rational protein crystallization.

The osmotic second virial coefficient, B(22), has become the quantity most widely used in developing a rational understanding of protein crystallization. In this work a novel method of measuring B22 using self-interaction chromatography (SIC) is presented that is at least an order of magnitude more efficient than traditional characterization methods, such as static light scattering. It is shown that SIC measurements of second virial coefficients for BSA are in quantitative agreement with static light scattering results. The measured virial coefficient for both BSA and myoglobin reveal a surprisingly narrow range of concentrations of ammonium sulfate that promote weakly attractive interactions that are optimal for crystallization. Using the virial coefficient information, myoglobin crystals were obtained by ultracentrifugal crystallization in a rational and rapid manner.

Animals↗
PubMed2003

Rationally selected basis proteins: a new approach to selecting proteins for spectroscopic secondary structure analysis.

Protein basis sets have been extensively used as reference data for the determination of protein structure with optical methods such as circular dichroism and infrared spectroscopies. We have taken a new approach to basis protein selection by utilizing three crystal structure classification databases: CATH, SCOP, and PDB_SELECT. Through the use of the information available in these and other online resources, we identified 115 commercially available proteins as potential basis set candidates. By carefully screening the quality of the crystal structures and commercial protein preparations, we obtained a final set of 50 rationally selected proteins (RaSP50) that has been optimized for use in spectroscopic protein structure determination studies. These proteins span the full range of known protein folds as well as alpha-helix and beta-sheet contents, and they represent a more comprehensive variety of fold types than any previous reference set. This report includes a detailed presentation of the reasoning behind the rational protein selection process, a description of the properties of the RaSP50 set, and a discussion of the types of structural and spectral variations that are represented in the set.

Circular Dichroism↗
PubMed2003

Prospects and limitations of the rational engineering of fibrillar collagens.

Recombinant collagens are attractive proteins for a number of biomedical applications. To date, significant progress was made in the large-scale production of nonmodified recombinant collagens; however, engineering of novel collagen-like proteins according to customized specifications has not been addressed. Herein we investigated the possibility of rational engineering of collagen-like proteins with specifically assigned characteristics. We have genetically engineered two DNA constructs encoding multi-D4 collagens defined as collagen-like proteins, consisting primarily of a tandem of the collagen II D4 periods that correspond to the biologically active region. We have also attempted to decrease enzymatic degradation of novel collagen by mutating a matrix metalloproteinase 1 cleavage site present in the D4 period. We demonstrated that the recombinant collagen alpha-chains consisting predominantly of the D4 period but lacking most of the other D periods found in native collagen fold into a typical collagen triple helix, and the novel procollagens are correctly processed by procollagen N-proteinase and procollagen C-proteinase. The nonmutated multi-D4 collagen had a normal melting point of 41 degrees C and a similar carbohydrate content as that of control. In contrast, the mutant multi-D4 collagen had a markedly lower thermostability of 36 degrees C and a significantly higher carbohydrate content. Both collagens were cleaved at multiple sites by matrix metalloproteinase 1, but the rate of hydrolysis of the mutant multi-D4 collagen was lower. These results provide a basis for the rational engineering of collagenous proteins and identifying any undesirable consequences of altering the collagenous amino acid sequences.

Amino Acids↗
PubMed2001

The rationality of resistance: alternatives for engagement in complex emergencies.

The different conceptualisations of conflict in the complex emergency literature have profound implications on the perception of the agency of different groups and the prospects for conflict management. While much recent analysis has focused on the rational political and economic functions of violence, relatively little analysis has focused on why the majority of people chose not to resort to violence. Using Foucault's analysis of power relations, a new framework for conflict analysis is proposed which includes non-violent resistance as well as violence as a means of domination. Non-violent resistance is explored as a rational, highly adaptable response to acts of domination. A comprehensive understanding of conflict must recognise local forms of resistance and identify the barriers and opportunities for the engagement of the international humanitarian community with these groups. This engagement can be used to foster capacities for the creation of legitimate, inclusive, non-violent political and economic processes in the attempt to provide alternatives for everyone in the conflict. If the purpose of the study of complex emergencies is to understand the nature of various conflicts and, based on that understanding, make recommendations for possible routes to conflict management, the analysis of local resistance and efforts to foster it must become a major aspect of the research agenda.

Altruism↗
PubMed1997

Liberal rationalism and medical decision-making.

I contrast Robert Veatch's recent liberal vision of medical decision-making with a more rationalist liberal model. According to Veatch, physicians are biased in their determination of what is in their patient's overall interests in favour of their medical interests. Because of the extent of this bias, we should abandon the practice of physicians offering what they guess to be the best treatment option. Patients should buddy up with physicians who share the same values -- 'deep value pairing'. The goal of choice is maximal promotion of patient values. I argue that if subjectivism about value and valuing is true, this move is plausible. However, if objectivism about value is true -- that there really are states which are good for people regardless of whether they desire to be in them -- then we should accept a more rationalist liberal alternative. According to this alternative, what is required to decide which course is best is rational dialogue between physicians and patients, both about the patient's circumstances and her values, and not the seeking out of people, physicians or others, who share the same values. Rational discussion requires that physicians be reasonable and empathic. I describe one possible account of a reasonable physician.

Coercion↗
PubMed1991

Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks.

Administration, Cutaneous↗
PubMed1996

Optimization of single-strand conformation polymorphism and sequence analysis of the mitochondrial control region in Pagellus bogaraveo (Sparidae, Teleostei): rationalized tools in fish population biology.

We report the isolation and sequencing of 400-550 base pairs (bp) of the mitochondrial DNA (mtDNA) control region of eight species of Sparidae (Perciformes, Teleostei). This sequence information allowed us to design specific primers to one of these species (Pagellus bogaraveo). The new set of primers was used to test a rationalized approach to study the mtDNA nucleotide variability at the intraspecific level. The single-strand conformation polymorphism (SSCP) technique was applied to detect sequence variation in two non-overlapping fragments of the control region of 32 individuals of P. bogaraveo. To assess the sensitivity of the method, the nucleotide sequence of the analysed region was determined for all the specimens. The results showed that, for one of the two fragments, SSCP analysis was able to detect 100% of the underlying genetic variability. In sharp contrast, nucleotide variation of the second DNA fragment was completely unresolved by SSCP under different experimental conditions. This suggests that the resolution power of SSCP is crucially dependent on the nature of the fragment subjected to the analysis; therefore, a preliminary test of the sensitivity of the method should be performed on each specific DNA fragment before starting a large-scale survey. A rationalized approach, combining the SSCP technique and a simplified sequencing procedure, is proposed for studying intraspecific polymorphism at the mtDNA control region in fish.

Animals↗
PubMed2005

Rational design of hypoallergens applied to the major cat allergen Fel d 1.

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.

Allergens↗
PubMed1983

Ritual and rational action in hospitals.

Menzies argues that nursing hierarchies and ritual practices protect nurses from the anxieties provoked by encountering human suffering. This proposition is examined with particular reference to ritual practices in nursing. It is argued that Menzies studied nurses in isolation from the societal and subcultural norms and values which direct hospital activity. Her psychodynamic model is contrasted with a sociological model of human conduct and action. The characteristics of ritual and rational action, and the difference between non-rational and irrational rituals, is explored. The findings of three 5-month periods of participant observation are presented as illustrative case material to support the authors view, that ritual procedures are not only defence mechanisms against anxiety, but social acts which generate and convey meaning. Ritual practices described in this analysis include rituals surrounding birth, death, status and power. It is concluded that if nurses wish to change or alter ritual nursing practices in hospital it is necessary to understand their social as well as their psychological meaning.

Anxiety↗
PubMed1991

Cultural and political limitations within a rational approach towards educational change.

This paper considers the use of a rational curriculum planning model within nurse education. It suggests that the process of change within the model is oversimplified and mechanistic. As such it denies or ignores the experience of individuals involved in the change process by reducing their personal, cultural and political realities to a level of idealogical control. The unrestrained or unmodified application of a rational approach may, by this control, inhibit the development of change arising from subjective experiences. It may further be viewed as a political strategy which benefits powerful groupings within the school thus institutionalizing this power and maintaining the status quo in terms of power and influence.

Conflict, Psychological↗
PubMed2006

Complete alanine scanning of the two-component lantibiotic lacticin 3147: generating a blueprint for rational drug design.

Lantibiotics are post-translationally modified antimicrobial peptides which are active at nanomolar concentrations. Some lantibiotics have been shown to function by targeting lipid II, the essential precursor of cell wall biosynthesis. Given that lantibiotics are ribosomally synthesized and amenable to site-directed mutagenesis, they have the potential to serve as biological templates for the production of novel peptides with improved functionalities. However, if a rational approach to novel lantibiotic design is to be adopted, an appreciation of the roles of each individual amino acid (and each domain) is required. To date no lantibiotic has been subjected to such rigorous analysis. To address this issue we have carried out complete scanning mutagenesis of each of the 59 amino acids in lacticin 3147, a two-component lantibiotic which acts through the synergistic activity of the peptides LtnA1 (30 amino acids) and LtnA2 (29 amino acids). All mutations were performed in situ in the native 60 kb plasmid, pMRC01. A number of mutations resulted in the elimination of detectable bioactivity and seem to represent an invariable core within these and related peptides. Significantly however, of the 59 amino acids, at least 36 can be changed without resulting in a complete loss of activity. Many of these are clustered to form variable domains within the peptides. The information generated in this study represents a blue-print that will be critical for the rational design of lantibiotic-based antimicrobial compounds.

Alanine↗
PubMed1988

Simplification of antiepileptic pharmacotherapy: from the viewpoint of rational management for epilepsy.

Rational management for epilepsy was investigated mainly from the viewpoint of antiepileptic pharmacotherapy. At first, diagnoses were reviewed by the ILAE classification for epilepsies and epileptic syndromes in 603 patients who visited a newly-established outpatient clinic for epilepsy and problems concerning the diagnosis of epilepsy were pointed out. Then, habitual pharmacotherapy in the past was assessed critically in cases where details of treatment before hospital attendance could be known. Further, the results of prospectively conducted simplification of pharmacotherapy where the appropriate choice of drugs and dosage were taken into account were reported. Furthermore, questions about the conventional criteria for drug effect evaluation were described and new criteria through which the influence on the daily life was also evaluated were presented. Finally, from the standpoint of comprehensive treatment, the system of rational management was discussed.

Anticonvulsants↗
PubMedDate not supplied

Vigabatrin: clinical evidence supporting rational polytherapy in management of uncontrolled seizures.

Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on "rational pharmacology," taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in approximately 50% of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in "socially integrated and active outpatients" as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had > 50% reduction in seizure frequency, and 10 of 19 (52%) had > 70% reduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Water intake and its thermal energy cost in reindeer fed lichen or various protein rations during winter.

Captive reindeer were fed four different rations which supplied equal energy but varying amount of crude protein: lichens (3%), mixed hay plus lichens (10%) and two feed concentrates with medium (12%) or high (18%) protein content. Kinetics of total body water were measured with tritiated water from February to March 1985, and thermal energy cost of daily water intake was estimated. Biological half-time of water was shorter, and daily water intake significantly higher on the hay plus lichens diet and on the medium- or high-protein concentrates diet than on the lichens diet during March 1985. Similar differences were found between reindeer on medium-protein concentrate and on lichens at the end of the corresponding feeding period during April 1986. Daily water inflow was positively correlated with a dietary supply of digestible crude protein (r = 0.916). Thermal energy costs of daily water intake were highest 1.9 MJ (3.7 l-1) in reindeer on high-protein concentrate during March 1985, and 2.0 MJ (3.9 l-1) in reindeer on medium-protein concentrate during April 1986. The reindeer fed on lichens had minimal and nearly twice as small thermal energy cost of daily water intake (mean 1.1 MJ 2.1 l-1) as on either of the concentrates. Our results show that even a moderate feed protein ration can significantly increase free water intake and its thermal energy cost in reindeer as compared to dominant natural feed (lichens) during winter. Careful protein supplementation is recommended to support body condition with a concomitant addition of easily soluble carbohydrates to compensate for increased thermal costs of water intake.

Animal Feed↗
PubMed2006

Frames, biases, and rational decision-making in the human brain.

Human choices are remarkably susceptible to the manner in which options are presented. This so-called "framing effect" represents a striking violation of standard economic accounts of human rationality, although its underlying neurobiology is not understood. We found that the framing effect was specifically associated with amygdala activity, suggesting a key role for an emotional system in mediating decision biases. Moreover, across individuals, orbital and medial prefrontal cortex activity predicted a reduced susceptibility to the framing effect. This finding highlights the importance of incorporating emotional processes within models of human choice and suggests how the brain may modulate the effect of these biasing influences to approximate rationality.

Adult↗
PubMed1976

Presence of bifidobacteria in the rumen of calves fed different rations.

A study was made on the numbers and species of bifidobacteria present in the rumen of calves fed high-roughage and high-concentrate diets. With the roughage ration the bifidobacteria were not detectable in a 10(-3) dilution, whereas with the concentrate ration their number was high, usually in the order of 10(8) to 10(9)/ml of rumen fluid. The species most represented, identified by means of deoxyribonucleic acid-deoxyribonucleic acid hybridization tests, included Bifidobacterium ruminale, Bifidobacterium globosum, and an apparently new species.

Actinomycetaceae↗
PubMed2003

Molecular mechanisms, diagnosis, and rational approaches to management of and therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies.

During the last decade, 18 genes and 11 additional loci harboring candidate genes have been associated with Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies. Ten of these 18 genes have been identified in the last 2 years. This phenomenal pace of CMT gene discovery has fomented an unprecedented explosion of information regarding peripheral nerve biology and its pathologic manifestations in CMT. This review integrates molecular genetics with the clinical phenotypes and provides a flowchart for molecular-based diagnostics. In addition, we discuss rational approaches to molecular therapeutics, including novel biologic molecules (eg, small interfering ribonucleic acid [siRNA], antisense RNA, and ribozymes) that potentially could be used as drugs in the future. These may be applicable in attempts to normalize gene expression in cases of CMT type 1A, wherein a 1.5 Mb genomic duplication causes an increase in gene dosage that is associated with the majority of CMT cases. Aggresome formation by the PMP22 gene product, the disease-associated gene in the duplication cases, could thus be avoided. We also discuss alternative therapeutics, in light of other neurodegenerative disorders, to disrupt such aggresomes. Finally, we review rational therapeutic approaches, including the use of antioxidants such as vitamin E, coenzyme Q10, or lipoic acid to relax potential oxidative stress in peripheral nerves, for CMT management.

Charcot-Marie-Tooth Disease↗