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PubMedDate not supplied

[The biophysical foundations of the localisation of encephalogram generators in the brain. The application of a distribution-type model to the localisation of epileptic foci].

INTRODUCTION: The brain electrical activity measured as the EEG signal is a powerful tool for the understanding of normal and pathological brain function. The EEG presents a high temporal resolution but a low spatial resolution. The latter can be improved solving the so-called inverse problem, if some a priori physiological and anatomical information is included. DEVELOPMENT: The present review presents the biophysical bases that allows brain source localization in realistic head models, as well as the two basic source models used: dipolar models and distributed source models. Finally, an example of practical application for the localization of epileptic focus using the distributed solution EPIFOCUS will be presented.

Brain↗

PubMed2005

A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs.

Heparan sulfate (HS) is an essential and dynamic regulator of fibroblast growth factor (FGF) signaling. Two fundamentally different crystallographic models have been proposed to explain, at the molecular level, how HS/heparin enables FGF and FGF receptor (FGFR) to assemble into a functional dimer on the cell surface. In the symmetric 'two-end' model, the heparin-binding sites of FGF and FGFR merge to form a basic canyon that recruits two HS for binding. Within this canyon, the HS molecules primarily act to orchestrate and fortify multivalent and cooperative protein-protein contacts within the dimer that are the foundations of dimerization. In contrast, in the asymmetric model, which mechanistically resembles the previously proposed trans FGF dimer model, a single heparin molecule facilitates dimerization by cross-linking two FGFs into a trans dimer that brings together the two FGFRs. Interestingly, the crystal structure upon which the asymmetric model is based contains a symmetric dimer reminiscent of the symmetric two-end model, suggesting that a different interpretation of the crystal structure has led to the postulation of the asymmetric model. Importantly, the symmetric two-end model provides an intriguing solution to the problem of how HS selectivity is achieved in FGF signaling. The model reveals that, within the canyon, FGF and FGFR no longer adhere to their individual HS binding specificities, but instead act in unison to search for a unique HS motif from a plethora of HS epitopes that are expressed in a tissue-specific and developmentally regulated fashion. Primary sequence differences within the heparin-binding sites of FGFs and FGFRs, together with ligand-induced changes in FGFR conformation, lead to the formation of distinct canyons with unique HS specificity for individual FGF-FGFR complexes.

Animals↗

PubMed2001

Acute exposure to extremely hazardous substances: an analysis of environmental equity.

Although environmental equity research has focused primarily on chronic pollution sources, recent advances in environmental modeling and geographic information systems (GIS) provide a foundation for developing measures that can be used to evaluate differential exposure to acute pollution events. This article describes a methodology that uses facility-specific information to develop a risk surface representing the spatial distribution of accidental exposure to hazardous substances in a study area. Environmental pollution models recommended by the U.S. Environmental Protection Agency were used in conjunction with GIS software to achieve this objective. The methodology was implemented in a large metropolitan region (Hillsborough County, Florida) to examine disproportionate exposure to worst-case releases of extremely hazardous substances. The environmental inequity hypothesis was investigated by directly comparing the distribution of potential exposures within each racial (non-White versus White) and income (below poverty versus above poverty) subgroup. The results indicate that a significantly large proportion of both non-White and impoverished individuals resided in areas potentially exposed to multiple accidental releases.

Environmental Exposure↗

PubMedDate not supplied

"Research" and "science" in the first half of the chiropractic century.

In the first 50 years of the chiropractic profession, a variety of unorthodox meanings for the terms "research," "science" and related words were in evidence. In harmony with popular conceptions of the day, science was constructed as a relatively static body of knowledge and was thought to reflect the will of God. Research was an ill-defined activity, and acquisition of new knowledge did not involve the experimental methodology that increasingly took hold in biology and medicine in the twentieth century. Chiropractors often viewed science and research as marketing strategies. Clinical data collection, when it occurred at all, was not described in sufficient detail to permit replication. Results were enthusiastically interpreted as indisputable proof of investigators' a priori assumptions about the effectiveness of chiropractic methods. A few in the profession recognized the general lack of understanding of the scientific method and sought reform from within. However, the colleges were unwilling to introduce coursework in research methods. At the end of World War II, the broad-scope national association of chiropractors in the United States established a nonprofit foundation for the purpose of raising funds for chiropractic research and education. Research plans were poorly conceived and grandiose: the first major initiative of the Chiropractic Research Foundation involved a nationwide publicity and fund-raising campaign modeled after the March of Dimes. When these efforts failed and the possibility of establishing free-standing research centers collapsed, the Foundation sought to shift responsibility for research to the schools. The poverty-stricken chiropractic colleges lacked the research sophistication for this task. Several more decades would pass before a sustained research effort and interest in clinical experimentation would become evident in chiropractic.

Chiropractic↗

PubMed2000

Fear and anxiety: animal models and human cognitive psychophysiology.

The aim of this paper is to explicate what is special about emotional information processing, emphasizing the neural foundations that underlie the experience and expression of fear. A functional, anatomical model of defense behavior in animals is presented and applications are described in cognitive and physiological studies of human affect. It is proposed that unpleasant emotions depend on the activation of an evolutionarily primitive subcortical circuit, including the amygdala and the neural structures to which it projects. This motivational system mediates specific autonomic (e.g., heart rate change) and somatic reflexes (e.g., startle change) that originally promoted survival in dangerous conditions. These same response patterns are illustrated in humans, as they process objective, memorial, and media stimuli. Furthermore, it is shown how variations in the neural circuit and its outputs may separately characterize cue-specific fear (as in specific phobia) and more generalized anxiety. Finally, again emphasizing links between the animal and human data, we focus on special, attentional features of emotional processing: The automaticity of fear reactions, hyper-reactivity to minimal threat-cues, and evidence that the physiological responses in fear may be independent of slower, language-based appraisal processes.

Animals↗

PubMed1999

Emerging strategies in the prevention of domestic violence.

Responses to domestic violence have focused, to date, primarily on intervention after the problem has already been identified and harm has occurred. There are, however, new domestic violence prevention strategies emerging, and prevention approaches from the public health field can serve as models for further development of these strategies. This article describes two such models. The first involves public health campaigns that identify and address the underlying causes of a problem. Although identifying the underlying causes of domestic violence is difficult--experts do not agree on causation, and several different theories exist--these theories share some common beliefs that can serve as a foundation for prevention strategies. The second public health model can be used to identify opportunities for domestic violence prevention along a continuum of possible harm: (1) primary prevention to reduce the incidence of the problem before it occurs; (2) secondary prevention to decrease the prevalence after early signs of the problem; and (3) tertiary prevention to intervene once the problem is already clearly evident and causing harm. Examples of primary prevention include school-based programs that teach students about domestic violence and alternative conflict-resolution skills, and public education campaigns to increase awareness of the harms of domestic violence and of services available to victims. Secondary prevention programs could include home visiting for high-risk families and community-based programs on dating violence for adolescents referred through child protective services (CPS). Tertiary prevention includes the many targeted intervention programs already in place (and described in other articles in this journal issue). Early evaluations of existing prevention programs show promise, but results are still preliminary and programs remain small, locally based, and scattered throughout the United States and Canada. What is needed is a broadly based, comprehensive prevention strategy that is supported by sound research and evaluation, receives adequate public backing, and is based on a policy of zero tolerance for domestic violence.

Adolescent↗

PubMed2000

Developmental dysplasia of the hip practice guideline: technical report. Committee on Quality Improvement, and Subcommittee on Developmental Dysplasia of the Hip.

OBJECTIVE: To create a recommendation for pediatricians and other primary care providers about their role as screeners for detecting developmental dysplasia of the hip (DDH) in children. PATIENTS: Theoretical cohorts of newborns. METHOD: Model-based approach using decision analysis as the foundation. Components of the approach include the following: PERSPECTIVE: Primary care provider. OUTCOMES: DDH, avascular necrosis of the hip (AVN). OPTIONS: Newborn screening by pediatric examination; orthopaedic examination; ultrasonographic examination; orthopaedic or ultrasonographic examination by risk factors. Intercurrent health supervision-based screening. PREFERENCES: 0 for bad outcomes, 1 for best outcomes. MODEL: Influence diagram assessed by the Subcommittee and by the methodology team, with critical feedback from the Subcommittee. EVIDENCE SOURCES: Medline and EMBASE search of the research literature through June 1996. Hand search of sentinel journals from June 1996 through March 1997. Ancestor search of accepted articles. EVIDENCE QUALITY: Assessed on a custom subjective scale, based primarily on the fit of the evidence to the decision model. RESULTS: After discussion, explicit modeling, and critique, an influence diagram of 31 nodes was created. The computer-based and the hand literature searches found 534 articles, 101 of which were reviewed by 2 or more readers. Ancestor searches of these yielded a further 17 articles for evidence abstraction. Articles came from around the globe, although primarily Europe, British Isles, Scandinavia, and their descendants. There were 5 controlled trials, each with a sample size less than 40. The remainder were case series. Evidence was available for 17 of the desired 30 probabilities. Evidence quality ranged primarily between one third and two thirds of the maximum attainable score (median: 10-21; interquartile range: 8-14). Based on the raw evidence and Bayesian hierarchical meta-analyses, our estimate for the incidence of DDH revealed by physical examination performed by pediatricians is 8.6 per 1000; for orthopaedic screening, 11.5; for ultrasonography, 25. The odds ratio for DDH, given breech delivery, is 5.5; for female sex, 4.1; for positive family history, 1.7, although this last factor is not statistically significant. Postneonatal cases of DDH were divided into mid-term (younger than 6 months of age) and late-term (older than 6 months of age). Our estimates for the mid-term rate for screening by pediatricians is 0.34/1000 children screened; for orthopaedists, 0.1; and for ultrasonography, 0.28. Our estimates for late-term DDH rates are 0.21/1000 newborns screened by pediatricians; 0.08, by orthopaedists; and 0.2 for ultrasonography. The rates of AVN for children referred before 6 months of age is estimated at 2.5/1000 infants referred. For those referred after 6 months of age, our estimate is 109/1000 referred infants. The decision model (reduced, based on available evidence) suggests that orthopaedic screening is optimal, but because orthopaedists in the published studies and in practice would differ, the supply of orthopaedists is relatively limited, and the difference between orthopaedists and pediatricians is statistically insignificant, we conclude that pediatric screening is to be recommended. The place of ultrasonography in the screening process remains to be defined because there are too few data about postneonatal diagnosis by ultrasonographic screening to permit definitive recommendations. These data could be used by others to refine the conclusions based on costs, parental preferences, or physician style. Areas for research are well defined by our model-based approach.

Decision Support Techniques↗

PubMed1992

The importance of maternal lineage on milk yield traits of dairy cattle.

Maternal lineage effects on milk yield traits, considered indicative of cytoplasmic inheritance, were evaluated with animal models. Cattle were from a selection experiment begun in 1968. Maternal pedigrees were traced to the first female member in the Holstein-Friesian Herdbook; purchased cows entering the herd, considered foundation females, were assigned to maternal lineage groups. All models accounted for year-season of calving, parity, and selection lines. Maternal lineage effects were included in a repeated records model with cow effects and preadjustment for sire and maternal grandsire transmitting abilities. Maternal lineage accounted for 5.2, 4.1, and 10.5% of phenotypic variation of preadjusted records of milk yield, fat yield, and fat percentage, respectively. Maternal lineage was evaluated as a fixed effect in an animal model including random animal and permanent environmental effects. Maternal lineage significantly affected fat percentage but not milk yield. Maternal genetic (nuclear) effects and their covariance with additive animal effects did not significantly account for additional variation nor did they influence maternal lineage estimates. Maternal lineage affected calculated net energy of milk but was not important for SNF yield or concentration. Maternal lineage influenced fat percentage, energy concentration, and, to a lesser extent, fat yield in milk of dairy cattle.

Animals↗

PubMed1997

Safety of in vivo adenovirus-mediated thymidine kinase treatment of oral cancer.

BACKGROUND: Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene (tk) is one of the most effective gene therapy strategies for solid tumors in experimental animal studies. Foundational animal studies in an oral cancer model have demonstrated significant antitumor effects and improved animal survival using this treatment strategy. OBJECTIVE: To assess the safety of adenovirus-mediated transfer of the herpes simplex virus tk gene for the treatment of oral cancer. DESIGN: Oral tumors were established in C3H/HeJ mice and were treated with tk followed by systemic ganciclovir administration. Polymerase chain reaction amplification techniques were used to screen local surrounding tissues and distant organs for the presence of the adenoviral construct. Microscopic examination of the tissues was performed to determine the cytopathic effects of the vector. Blood samples were obtained from the animals to test for liver, renal, and bone marrow function after treatment. RESULTS: The adenoviral vector was present in the livers, lungs, and kidneys of animals treated with the maximal single injection dose of 2 x 10(9) plaque forming units (pfu). No vector was noted systemically after delivery of an equally effective low dose of 1 x 10(8) pfu. Microscopic examination revealed no cytopathic effects in distant organs despite the presence of vector. Results of liver and renal function tests revealed no differences between treated and control animals. There was no statistical difference in white blood cell count, hematocrit, or platelet count between animals treated with ganciclovir and control animals. CONCLUSIONS: Based on these results, the direct delivery of adenovirus-tk followed by ganciclovir administration appears both efficacious and safe in an animal model. However, serum evaluation for adenovirus vector and screening organ function studies should be included in human protocols using this gene therapy scheme.

Adenoviruses, Human↗

PubMed2006

Research on psychoneuroimmunology: tai chi as a stress management approach for individuals with HIV disease.

Psychoneuroimmunology is a framework for mind-body practice and research that combines cutting-edge scientific exploration with holistic philosophy to appreciate and understand stress responses. The rapidly growing research literature provides a foundation for building an integrative stress management model with the potential to positively influence the stress-disease relationship and, ultimately, health outcomes. This article introduces a novel tai chi intervention and provides quantitative and qualitative data from a randomized clinical trial indicating its effects on psychosocial variables in individuals living with various stages of HIV disease.

Adaptation, Psychological↗

PubMed2006

Analysis of apoptotic cell death, Bcl-2, and p53 protein expression in freshly fixed and cryopreserved ovarian tissue after exposure to warm ischemia.

OBJECTIVE: To evaluate the effect of ischemia time on the expression of Bcl-2 and p53 proteins on freshly fixed and cryopreserved-thawed ovarian tissue. DESIGN: Experimental study using porcine animal model. SETTING: Biological Resources Unit, Cleveland Clinic Foundation. ANIMAL(S): Eight nonpregnant adult sows. INTERVENTION(S): Bilateral oophorectomy was performed in eight sows and the ovaries were subjected to time-dependent (1, 10, 20, and 30 min) warm ischemia (room temperature). Each specimen was divided into two parts, One was fixed as a fresh tissue (freshly fixed) and the other was subjected to cryopreservation, thawing, and fixation (cryopreserved). MAIN OUTCOME MEASURE(S): Apoptosis (TUNEL assay) and Bcl-2 and p53 protein expression (immunoperoxidase method) were assessed. RESULT(S): At 1, 10, 20, 30 min of warm ischemia the apoptotic indices were: 1) statistically significantly higher in the atretic (1.36 +/- 0.20, 1.59 +/- 0.20, 1.67 +/- 0.22, and 1.67 +/- 0.24, respectively) than in the nonatretic follicles (0.69 +/- 0.06, 0.69 +/- 0.06, 0.76 +/-, and 0.06, 0.71 +/- 0.06, respectively; P<.05); 2) not significantly different between freshly fixed and cryopreserved tissues; and 3) nonsignificantly higher with the increased duration of ischemia. Bcl-2 expression was seen in the granulosa but not in the theca cells of most of the healthy and occasional atretic follicles. p53 expression was seen only in few atretic follicles. Increased duration of ischemia was associated with insignificant incremental rise of the number of follicles with Bcl-2 expression (1.82 +/- 0.30, 2.01 +/- 0.44, 2.02 +/- and 0.35, 2.05 +/- 0.42 for healthy follicles at 1, 10, 20, and 30 min, respectively; P=.99). CONCLUSION(S): (1) Apoptosis is involved in follicular atresia; (2) Bcl-2 is induced by warm ischemia; and (3) cryopreservation insult does not alter the apoptotic signals with short tissue preparation time.

Animals↗

PubMed2005

Design and optimization of a recombinant system for large-scale production of the MPT64 antigen from Mycobacterium tuberculosis.

Early clinical trials of a potential new tuberculosis (TB) diagnostic, the Patch Test for Active TB (PTAT), used MPB64 protein that was purified from the spent medium of Bacillus Calmette-Guérin (BCG) Tokyo 172 vaccine production. The yield was poor, 0.05 mg/L, and the process for purification of the protein was complex, requiring four chromatographic steps. The combination of yield and purification complexity compromised the ability to produce the PTAT diagnostic in quantities sufficient for larger clinical trials and commercialization. We report here a highly efficient method for the overexpression and purification of recombinant MPT64 from Escherichia coli (rMPT64) based upon a mild insolubility of rMPT64 following induction, and scalable anion-exchange and gel filtration chromatographies. Yields of protein were improved substantially to approximately 250 mg/L, and resulted in a preparation greater than 98% pure. Quantitative release assays were developed and used with MALDI-TOF mass spectrometry to confirm the identity of rMPT64. Using a guinea pig model of active TB, we found that rMPT64 elicited a specific immune response indistinguishable from that of MPB64 purified from BCG Tokyo culture filtrates. These results describe the first efficient and scalable protocol for production of rMPT64, demonstrate its activity in an animal model of active TB, and lay the foundation of ongoing and future use of the PTAT in clinical settings.

Amino Acid Sequence↗

PubMed1998

Solving belief problems: toward a task analysis.

Solving belief problems develops as a skill in normal children during the preschool years. To understand this process of development, it is necessary to provide an analysis of the tasks used to test preschool 'theory of mind' skills. This analysis should allow us to relate the structure of a given task to the underlying cognitive mechanisms that the task engages. In two experiments, we find that 3-year-old children show a pattern of success and failure on belief tasks that is not consistent with 'conceptual deficit' accounts. Young children possess the concept, BELIEF, but have certain characteristic difficulties with correctly calculating the contents of beliefs. In childhood autism, by contrast, the mechanisms that in normal development bestow conceptual competence in this domain are impaired. In the first experiment, parallel task structures are used to show that 3-year-olds are no better at predicting behavior from a partially true belief than they are at predicting behavior from an entirely false belief. We develop specific proposals about task structural factors that either facilitate or hinder success in belief-content calculation. These proposals are supported in a second experiment. We compare two false-belief tasks, one of which has helpful structural factors, the other of which has hampering factors, with a third task which exemplifies a hampering task structure but without any theory of mind content. We compare 3- and 4-year-olds' patterns of performance with that of autistic children. Each of the three groups shows a distinct performance profile across the three tasks, as predicted for each case by our model. Innate attentional mechanisms provide the conceptual foundations for 'theory of mind' but must be supplemented by a robust executive process that allows false beliefs to achieve 'conceptual pop-out.' Our approach has general implications for the study of conceptual development.

Autistic Disorder↗

PubMed2001

The design of self-replicating helical peptides.

The self-assembly of helical peptides and information transfer through autocatalysis and cross-catalysis are the foundation of peptide-based molecular evolution models. Many fundamental properties of living systems, such as environmental sensitivity, chiroselectivity, cross-catalysis, dynamic error correction and conditional selection, are exhibited by various self-replicating peptide systems. Recently, advances have been made in the design of peptide systems with autocatalytic and cross-catalytic properties.

Amino Acid Sequence↗

PubMed1989

The cellular immunotherapy of cancer: current and potential uses of interleukin-2.

The potential for immune-mediated destruction of neoplasms was suggested nearly one century ago. Despite this, no "magic bullet" has yet been identified. Nevertheless, the physiology of cell-mediated immune reactions has been well characterized in molecular, cellular, and clinical studies of allograft and microbial immunity. Extensive studies performed in laboratory animal models have documented the in vitro and in vivo destruction of various neoplastic tissues by immune cells. This destruction can be directed against autologous, syngeneic, or allogeneic tumors in several systems with varying degrees of "tumor specificity". Two approaches exist towards utilizing these immune reaction in vivo. The first involves providing the tumor bearer with immunostimulatory agents, either specific or nonspecific, designed to activate and amplify the destructive potential of the individual's endogenous immune cells able to recognize and destroy autologous tumor. The second approach provides immune cells with antitumor capacity to a tumor-bearing individual, these cells having been activated exogenously. A number of successful regimens involving these two approaches, and combinations of them, have been delineated in animal tumor models. These experimental studies lay a strong foundation for initiating clinical trials of these concepts for patients with cancer. This review summarizes the diverse experimental studies in animals leading to clinical trials, presents recent data from ongoing clinical trials directly testing the potential for cellular immunotherapy, and then presents some of the major challenges facing further development and application of this potential therapeutic approach.

Animals↗

PubMed2001

Potentiometric polymeric membrane electrodes for measurement of environmental samples at trace levels: new requirements for selectivities and measuring protocols, and comparison with ICPMS.

It is here established that potentiometric polymeric membrane electrodes based on electrically neutral ionophores are useful analytical tools for heavy metal ion determinations in drinking water at nanomolar total concentrations. This means that they can compete with the most sophisticated techniques of instrumental analysis. With optimized ion-selective membranes based on the lead-selective ionophore 4-tert-butylcalix[4]arenetetrakis(thioacetic acid dimethylamide) as model example, a number of native and spiked drinking water samples are potentiometrically assessed for lead, and the results compared with ICPMS measurements. The goal of this work is to demonstrate that detection limits in real world samples are routinely achieved that are, with 1.5 ppb, at least 10-fold lower than the lead action limit imposed by the U.S. Environmental Protection Agency (15 ppb). In contrast to earlier reports, different conditioning and measuring protocols are followed, and membranes and inner filling solution of optimized composition are used. The sensors are shown to be useful for the speciation analysis of lead in water as well. Typical water samples are acidified to pH 4 to assess total lead rather than free, uncomplexed lead. For lead concentrations above 2 ppb, the values compare very well with ICPMS. Main interferences are found to be H+ and Cu2+, although Cu2+ only shows significant interference at levels around or above its own action limit (1.3 ppm), in which case the water sample would anyway show quality problems. An explicit, simplified flux model targeted to the practical use of these sensors explains the extent of expected interference. Sensors are shown to require a higher selectivity than predicted by models not considering ion fluxes, since in dilute samples, the counterdiffusion flux of lead from the membrane into the sample becomes potential determining. The model and experiments shown here are a foundation for future trace level applications of potentiometric polymeric membrane electrodes.

Algorithms↗

PubMed1999

Retro Models of Pt Anticancer Drug DNA Adducts: Chirality-Controlling Chelate Ligand Restriction of Guanine Dynamic Motion in (2,2'-Bipiperidine)PtG(2) Complexes (G = Guanine Derivative).

Features of cisplatin-type anticancer drug adducts with nucleic acids and their constituents are clouded because they exist as a fluxional mixture of conformers. Retro-model adducts containing the specially designed chiral diamine ligand, Bip = 2,2'-bipiperidine, are dramatically less fluxional. Conformers of BipPtG(2) adducts with R,S,S,R and S,R,R,S asymmetric centers at the N, C, C, and N Bip chelate ring atoms and G = 5'-GMP, 5'-dGMP, 3'-GMP, or 9-ethylguanine are amenable to separate characterization. All possible BipPtG(2) atropisomers (one head-to-head (HH) and Delta and Lambda head-to-tail (HT) atropisomers) were observed by NMR spectroscopy. At equilibrium at low pH, one HT atropisomer dominates. CD spectra, G H8 chemical shifts, and low-pH equilibria of BipPtG(2) and Me(2)()DABPtG(2) (Me(2)()DAB = N,N '-dimethyl-2,3-diaminobutane) are similar when the chelate ring atoms have the same stereochemistries; thus, Bip and Me(2)()DAB are termed chirality-controlling chelates (CCC) since these ligands dictate the absolute conformation of the major HT rotamer. In each case, the HT conformer that cannot form G O6-NH(CCC) hydrogen bonds was dominant, and the G H8 chemical shift indicated that this conformer had less tilted bases, allowing favorable base-base dipole-dipole interactions. For both the R,S,S,R and S,R,R,S Bip chiralities of the BipPt(3'-GMP)(2) complexes, the percentage of DeltaHT rotamer increased near pH 7, a probable consequence of phosphate-cis-G hydrogen bonds accompanied by favorable dipole interactions of less tilted bases. For the 5'-GMP complexes, these factors favor the LambdaHT rotamer near pH 7. When G has a 5'-phosphate group, rotamer distribution is also influenced by phosphate-NH(Bip) hydrogen bonds. At high pH, the nature and/or strength of interactions such as G dipole-G dipole interactions and G O6-NH(Bip) and phosphate-cis-G hydrogen bonding are altered by G N(1)H deprotonation. The features of the complexes at high pH can be largely explained as arising from the net result of these interactions. This information from retro models with a CCC ligand lays the foundation for understanding and evaluating the properties of the highly dynamic adducts of anticancer drugs.

Journal Article↗

PubMed2004

Employee commitment and motivation: a conceptual analysis and integrative model.

Theorists and researchers interested in employee commitment and motivation have not made optimal use of each other's work. Commitment researchers seldom address the motivational processes through which commitment affects behavior, and motivation researchers have not recognized important distinctions in the forms, foci, and bases of commitment. To encourage greater cross-fertilization, the authors present an integrative framework in which commitment is presented as one of several energizing forces for motivated behavior. E. A. Locke's (1997) model of the work motivation process and J. P. Meyer and L. Herscovitch's (2001) model of workplace commitments serve as the foundation for the development of this new framework. To facilitate the merger, a new concept, goal regulation, is derived from self-determination theory (E. L. Deci & R. M. Ryan, 1985) and regulatory focus theory (E. I. Higgins, 1997). By including goal regulation, it is acknowledged that motivated behavior can be accompanied by different mindsets that have particularly important implications for the explanation and prediction of discretionary work behavior.

Employment↗