Showing papers by "University College London published in 1997"
TL;DR: Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
Abstract: The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
4,558 citations
TL;DR: Various applications of pAx measurements are discussed based on the hypothesis that drugs and drug antagonists compete for receptors according to the mass law, and a new measure, pAh, is introduced to express the activity of unsurmountable antagonists.
Abstract: Various applications of pAx measurements are discussed based on the hypothesis that drugs and drug antagonists compete for receptors according to the mass law. Examples are given illustrating the use of pAx measurements to identify agonists which act on the same receptors and to compare the receptors of different tissues. Tests of competitive and noncompetitive antagonism are considered in relation to the antagonisms acetylcholine-atropine, histamine-atropine and acetylcholine-cinchonidine. A new measure, pAh, is introduced to express the activity of unsurmountable antagonists.
3,531 citations
TL;DR: In this article, the authors developed a theory of the allocation of formal authority and real authority within organizations, and illustrated how a formally integrated structure can accommodate various degrees of "real" integration.
Abstract: This paper develops a theory of the allocation of formal authority (the right to decide) and real authority (the effective control over decisions) within organizations, and it illustrates how a formally integrated structure can accommodate various degrees of "real" integration. Real authority is determined by the structure of information, which in turn depends on the allocation of formal authority. An increase in an agent's real authority promotes initiative but results in a loss of control for the principal. After spelling out (some of) the main determinants of the delegation of formal authority within organizations, the paper examines a number of factors that increase the subordinates' real authority in a formally integrated structure: overload, lenient rules, urgency of decision, reputation, performance measurement, and multiplicity of superiors. Finally, the amount of communication in an organization is shown to depend on the allocation of formal authority.
2,959 citations
TL;DR: Because of the limited number of references allowed, the authors were unable to cite many important papers; they apologize to their authors.
2,737 citations
TL;DR: Analysis of the structural families generated by CATH reveals the prominent features of protein structure space and a database of well-characterised protein structure families will facilitate the assignment of structure-function/evolution relationships to both known and newly determined protein structures.
2,551 citations
TL;DR: In this paper, the authors observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to 157 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype.
2,223 citations
TL;DR: Although both IL-6 and TNF alpha are expressed by adipose tissue, the results show that there are important differences in their systemic release.
Abstract: We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.
2,169 citations
TL;DR: It is proposed that the degree of immersion can be objectively assessed as the characteristics of a technology, and has dimensions such as the extent to which a display system can deliver an inclusive, extensive, surrounding, and vivid illusion of virtual environment to a participant.
Abstract: This paper reviews the concepts of immersion and presence in virtual environments VEs. We propose that the degree of immersion can be objectively assessed as the characteristics of a technology, and has dimensions such as the extent to which a display system can deliver an inclusive, extensive, surrounding, and vivid illusion of virtual environment to a participant. Other dimensions of immersion are concerned with the extent of body matching, and the extent to which there is a self-contained plot in which the participant can act and in which there is an autonomous response. Presence is a state of consciousness that may be concomitant with immersion, and is related to a sense of being in a place. Presence governs aspects of autonomie responses and higher-level behaviors of a participant in a VE. The paper considers single and multiparticipant shared environments, and draws on the experience of ComputerSupported Cooperative Working CSCW research as a guide to understanding presence in shared environments. The paper finally outlines the aims of the FIVE Working Group, and the 1995 FIVE Conference in London, UK.
1,809 citations
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TL;DR: In this article, a version of the neoclassical growth model is used in which the key feature of aggregate technology is capital-skill complementarity: the elasticity of substitution is higher between capital equipment and unskilled workers than between skilled workers and capital equipment.
Abstract: The notion of skilled-biased technological change is often held responsible for the recent behavior of the U.S. skill premium, or the ratio between the wages of skilled and unskilled labor. This paper develops a framework for understanding this notion in terms of observable variables and uses the framework to evaluate the fraction of the skill premium's variation that is caused by changes in observables. A version of the neoclassical growth model is used in which the key feature of aggregate technology is capital-skill complementarity: the elasticity of substitution is higher between capital equipment and unskilled labor than between capital equipment and skilled labor. With this feature, changes in observables can account for nearly all the variation in the skill premium over the last 30 years. This finding suggests that increased wage inequality results from economic growth driven by new, efficient technologies embodied in capital equipment.
1,607 citations
TL;DR: In this article, the authors trace the relationship between attachment processes and the development of the capacity to envision mental states in self and others, and suggest that the ability to mentalize, to represent behavior in terms of mental states, or to have a theory of mind is a key determinant of self-organization.
Abstract: The paper traces the relationship between attachment processes and the development of the capacity to envision mental states in self and others. We suggest that the ability to mentalize, to represent behavior in terms of mental states, or to have “a theory of mind” is a key determinant of self-organization which is acquired in the context of the child’s early social relationships. Evidence for an association between the quality of attachment relationship and reflective function in the parent and the child is reviewed and interpreted in the context of current models of theory of mind development. A model of the development of self-organization is proposed which has at its core the caregiver’s ability to communicate understanding of the child’s intentional stance. The implications of the model for pathological self-development are explored, with specific reference to the consequences of maltreatment.
1,482 citations
TL;DR: To the authors' knowledge, this is the first nonsyndromic sensorineural autosomal deafness susceptibility gene to be identified, which implicates Cx26 as an important component of the human cochlea.
Abstract: Severe deafness or hearing impairment is the most prevalent inherited sensory disorder, affecting about 1 in 1,000 children. Most deafness results from peripheral auditory defects that occur as a consequence of either conductive (outer or middle ear) or sensorineuronal (cochlea) abnormalities. Although a number of mutant genes have been identified that are responsible for syndromic (multiple phenotypic disease) deafness such as Waardenburg syndrome and Usher 1B syndrome, little is known about the genetic basis of non-syndromic (single phenotypic disease) deafness. Here we study a pedigree containing cases of autosomal dominant deafness and have identified a mutation in the gene encoding the gap-junction protein connexin 26 (Cx26) that segregates with the profound deafness in the family. Cx26 mutations resulting in premature stop codons were also found in three autosomal recessive non-syndromic sensorineuronal deafness pedigrees, genetically linked to chromosome 13q11-12 (DFNB1), where the Cx26 gene is localized. Immunohistochemical staining of human cochlear cells for Cx26 demonstrated high levels of expression. To our knowledge, this is the first non-syndromic sensorineural autosomal deafness susceptibility gene to be identified, which implicates Cx26 as an important component of the human cochlea.
TL;DR: In this paper, a model of consumer demand that is consistent with the observed expenditure patterns of individual consumers in a long time series of expenditure surveys and is also able to provide a detailed welfare analysis of shifts in relative prices is presented.
Abstract: This paper presents a model of consumer demand that is consistent with the observed expenditure patterns of individual consumers in a long time series of expenditure surveys and is also able to provide a detailed welfare analysis of shifts in relative prices. A nonparametric analysis of consumer expenditure patterns suggests that Engel curves require quadratic terms in the logarithm of expenditure. While popular models of demand such as the Translog or the Almost Ideal Demand Systems do allow flexible price responses within a theoretically coherent structure, they have expenditure share Engel curves that are linear in the logarithm of total expenditure. We derive the complete class of integrable quadratic logarithmic expenditure share systems. A specification from this class is estimated on a large pooled data set of U.K. households. Models that fail to account for Engel curvature are found ro generate important distortions in the patterns of welfare losses associated with a tax increase.
TL;DR: In this study, it is shown that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range.
TL;DR: Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp 90 and not the binding to incompletely folded client polypeptides as previously suggested.
TL;DR: Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment, and from factors that act early in life, as represented by physical height.
TL;DR: Any assessment of medical or surgical therapeutic response requires a method of quantifying disease severity that will be widely accepted by practitioners in the field, and this acceptance will largely depend on how easy the method is to apply.
Abstract: Interest in the surgical treatment of chronic rhinosinusitis has increased, primarily because rigid endoscopy and, more particularly, computed tomographic scanning have facilitated the visualization of disease. At the same time it has become both scientifically and financially imperative to audit therapeutic outcome. Consequently, a staging system for nonneoplastic sinus disease is needed. It is clear that any assessment of medical or surgical therapeutic response requires a method of quantifying disease severity that will be widely accepted by practitioners in the field. This acceptance will largely depend on how easy the method is to apply. With computed tomographic scanning it is possible to more accurately determine the extent of the pathologic condition in rhinosinusitis, a disease in which the severity of symptoms and the appearances on nasal endoscopy have a significantly more unpredictable correlation with the extent of disease. One goal of the Task Force on Rhinosinusitis of the American Academy of Otolaryngology-Head and Neck Surgery was to recommend a system for outcomes research that combines quantification with ease of application.
TL;DR: In this article, it is shown that the principle can be justified under certain assumptions, but that in cases where these assumptions do not hold, the principle is not valid, and the major problem appears to lie in the way the principle considers each document independently of the rest.
Abstract: The principle that, for optimal retrieval, documents should be ranked in order of the probability of relevance or usefulness has been brought into question by Cooper. It is shown that the principle can be justified under certain assumptions, but that in cases where these assumptions do not hold, the principle is not valid. The major problem appears to lie in the way the principle considers each document independently of the rest. The nature of the information on the basis of which the system decides whether or not to retrieve the documents determines whether the document‐by‐document approach is valid.
TL;DR: The pathways by which mammalian Ras proteins induce cortical actin rearrangement and cause cellular transformation are investigated using partial loss of function mutants of Ras and activated and inhibitory forms of various postulated target enzymes for Ras.
TL;DR: The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.
Abstract: OBJECTIVE: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants. DESIGN: Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years. SETTING: London based office staff in 20 civil service departments. SUBJECTS: 10,308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%). MAIN OUTCOME MEASURES: New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event. RESULTS: Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease. CONCLUSIONS: Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.
TL;DR: In this article, an R -squared measure of goodness of fit for the class of exponential family regression models, which includes logit, probit, Poisson, geometric, gamma, and exponential, was proposed.
TL;DR: In this article, it was shown that the presence of local Ising anisotropy leads to a geometrically frustrated ground state, preventing long-range magnetic order down to at least 0.05 K. But unlike in the case of a frustrated antiferromagnet, this disorder is principally static.
Abstract: We report a detailed study of the pyrochlore ${\mathrm{Ho}}_{2}{\mathrm{Ti}}_{2}{\mathrm{O}}_{7}$, in which the magnetic ions $({\mathrm{Ho}}^{3+})$ are ferromagnetically coupled with $J\ensuremath{\sim}1\mathrm{K}$. We show that the presence of local Ising anisotropy leads to a geometrically frustrated ground state, preventing long-range magnetic order down to at least 0.05 K. However, unlike in the case of a frustrated antiferromagnet, this disorder is principally static. In a magnetic field, the ground-state degeneracy is broken and ordered magnetic phases are formed which display an unusual history dependence due to the slow dynamics of the system. These results represent the first experimental evidence for geometrical frustration in a ferromagnetic system.
TL;DR: For instance, this paper used PET to image the neural system underlying visuospatial attention and found that the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices were observed to form the core of a neural network for spatial attention.
Abstract: PET was used to image the neural system underlying visuospatial attention. Analysis of data at both the group and individual-subject level provided anatomical resolution superior to that described to date. Six right-handed male subjects were selected from a pilot behavioural study in which behavioural responses and eye movements were recorded. The attention tasks involved covert shifts of attention, where peripheral cues indicated the location of subsequent target stimuli to be discriminated. One attention condition emphasized reflexive aspects of spatial orientation, while the other required controlled shifts of attention. PET activations agreed closely with the cortical regions recently proposed to form the core of a neural network for spatial attention. The two attention tasks evoked largely overlapping patterns of neural activation, supporting the existence of a general neural system for visuospatial attention with regional functional specialization. Specifically, neocortical activations were observed in the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices (Brodmann area 6).
TL;DR: The Raman spectra of over 60 pigments, both natural and synthetic, known to have been in use before ≈ 1850 AD, have been studied by Raman microscopy.
TL;DR: Qualitative methods aim to make sense of phenomena in terms of the meanings people bring to them and use “a holistic perspective which preserves the complexities of human behaviour.”
Abstract: Epidemiologist Nick Black has argued that a finding or a result is more likely to be accepted as a fact if it is quantified (expressed in numbers) than if it is not1 There is little or no scientific evidence, for example, to support the well known “facts” that one couple in 10 is infertile, or that one man in 10 is homosexual Yet, observes Black, most of us are happy to accept uncritically such simplified, reductionist, and blatantly incorrect statements so long as they contain at least one number
Researchers who use qualitative methods seek a deeper truth They aim to “study things in their natural setting, attempting to make sense of, or interpret, phenomena in terms of the meanings people bring to them,”2 and they use “a holistic perspective which preserves the complexities of human behaviour”1
#### Summary points
Qualitative methods aim to make sense of, or interpret, phenomena in terms of the meanings people bring to them
Qualitative research may define preliminary questions which can then be addressed in quantitative studies
A good qualitative study will address a clinical problem through a clearly formulated question and using more than one research method (triangulation)
Analysis of qualitative data can and should be done using explicit, systematic, and reproducible methods
Questions such as “How many parents would consult their general practitioner when their child has a mild temperature?” or “What proportion of smokers have tried to give up?” clearly need answering through quantitative methods But questions like “Why do parents worry so much about their children's temperature?” and “What stops people giving up smoking?” cannot and should not be answered by leaping in and measuring the first aspect of the problem that we (the outsiders) think might be important Rather, we need to listen to what people have to say, …
TL;DR: Rho, Rac and Cdc42 are three Ras-related GTP-binding proteins that control the assembly and disassembly of the actin cytoskeleton in response to extracellular signals as discussed by the authors.
TL;DR: Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay.
Abstract: Objectives: To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture. Design: Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period. Setting: Teaching hospital, London. Subjects: 40 patients undergoing repair of proximal femoral fracture under general anaesthesia. Interventions: Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients). Main outcome measures: Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes. Results: Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (−5 ml (−10 to 1 ml) and −0.4 l/min (−1.0 to 0.2 l/min)) (P Conclusions: Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay. Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery, but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital stay
TL;DR: The data showed that the concerted action of Rho and Rac modulate the establishment of cadherin adhesion: a constitutively active form of Rac was not sufficient to stabilize cadherindependent cell–cell contacts when endogenous Rho was inhibited.
Abstract: Cadherins are calcium-dependent cell–cell adhesion molecules that require the interaction of the cytoplasmic tail with the actin cytoskeleton for adhesive activity. Because of the functional relationship between cadherin receptors and actin filament organization, we investigated whether members of the Rho family of small GTPases are necessary for cadherin adhesion. In fibroblasts, the Rho family members Rho and Rac regulate actin polymerization to produce stress fibers and lamellipodia, respectively. In epithelial cells, we demonstrate that Rho and Rac are required for the establishment of cadherin-mediated cell–cell adhesion and the actin reorganization necessary to stabilize the receptors at sites of intercellular junctions. Blocking endogenous Rho or Rac selectively removed cadherin complexes from junctions induced for up to 3 h, while desmosomes were not perturbed. In addition, withdrawal of cadherins from intercellular junctions temporally precedes the removal of CD44 and integrins, other microfilament-associated receptors. Our data showed that the concerted action of Rho and Rac modulate the establishment of cadherin adhesion: a constitutively active form of Rac was not sufficient to stabilize cadherindependent cell–cell contacts when endogenous Rho was inhibited. Upon induction of calcium-dependent intercellular adhesion, there was a rapid accumulation of actin at sites of cell–cell contacts, which was prevented by blocking cadherin function, Rho or Rac activity. However, if cadherin complexes are clustered by specific antibodies attached to beads, actin recruitment to the receptors was perturbed by inhibiting Rac but not Rho. Our results provide new insights into the role of the small GTPases in the cadherin-dependent cell– cell contact formation and the remodelling of actin filaments in epithelial cells.
TL;DR: This introductory article is to provide an overview of transcription factors, their mechanism of action, their regulation and the manner in which alterations in them can result in disease.
TL;DR: A version of Bush and Mosteller's stochastic learning theory in the context of games is considered and it is shown that in the continuous time limit the biological model coincides with the deterministic, continuous time replicator process.
TL;DR: Three large sample studies, one British and two American, brought together for their complementarity in samples, measures, and design, all show similar social gradients for adult men and women in physical and mental morbidity and in psychological well-being, suggesting that indirect selection cannot account for inequalities in health.