Showing papers by "King's College London published in 1995"
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01 Jan 1995TL;DR: In this paper, the authors provide global and asymptotic estimates for the eigenvalues of - + q when q is real and for -+ q when 1 is complete.
Abstract: Linear operations in Banach spaces Entropy numbers, s-numbers, and eigenvalues Unbounded linear operators Sesquilinear forms in Hilbert spaces Sobolev spaces Generalized Dirichlet and Neumann boundary-value problems Second-order differential operators on arbitrary open sets Capacity and compactness criteria Essential spectra Essential spectra of general second-order differential operators Global and asymptotic estimates for the eigen-values of - + q when q is real. Estimates for the singular values of - + q when 1 is complete Bibliography Notation index Subject index
1,792 citations
TL;DR: The recent discovery of two other MAPK subtypes, the JNK/SAPK subfamily and p38/RK (mammalian equivalents of HOG1 in yeast), reveals extreme complexity within the family and the existence in mammalian cells of parallel MAPK cascades that can be activated simultaneously.
1,028 citations
TL;DR: The pharmacological properties of the oil support the traditional use of N. sativa and its derived products as a treatment for rheumatism and related inflammatory diseases and is greater than is expected from its content of thymoquinone.
Abstract: Samples of the expressed fixed oil from different sources of Nigella sativa seeds were examined by thin-layer and gas chromatography for content of fixed oils and thymoquinone, and these substances were tested as possible inhibitors of eicosanoid generation and membrane lipid peroxidation The crude fixed oil and pure thymoquinone both inhibited the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism in rat peritoneal leukocytes stimulated with calcium ionophore A23187, as shown by dose-dependent inhibition of thromboxane B2 and leukotriene B4, respectively Thymoquinone was very potent, with approximate IC50 values against 5-lipoxygenase and cyclo-oxygenase of < 1 microgram/ml and 35 micrograms/ml, respectively Both substances also inhibited non-enzymatic peroxidation in ox brain phospholipid liposomes, but thymoquinone was about ten times more potent However, the inhibition of eicosanoid generation and lipid peroxidation by the fixed oil of N sativa is greater than is expected from its content of thymoquinone (ca 02% w/v), and it is possible that other components such as the unusual C20:2 unsaturated fatty acids may contribute also to its anti-eicosanoid and antioxidant activity These pharmacological properties of the oil support the traditional use of N sativa and its derived products as a treatment for rheumatism and related inflammatory diseases
850 citations
TL;DR: If 'burnout' and psychiatric disorder among cancer clinicians are to be reduced, increased resources will be required to lessen overload and to improve training in communication and management skills.
Abstract: The prevalence and causes of 'burnout' and psychiatric disorder among senior oncologists and palliative care specialists have been measured in a national questionnaire-based survey. All consultant non-surgical oncologists in the UK were asked to participate. Sources of work-related stress and satisfaction were measured using study-specific questions which were aggregated into factors. Psychiatric disorder was estimated using the 12-item General Health Questionnaire. The three components of 'burnout'--emotional exhaustion, depersonalisation and low personal accomplishment--were assessed using the Maslach Burnout Inventory. Three hundred and ninety-three out of 476 (83%) consultants returned their questionnaires. The estimated prevalence of psychiatric disorder in cancer clinicians was 28%, and this is similar to the rate among British junior house officers. The study group had equivalent levels of emotional exhaustion and low personal accomplishment to those found in American doctors and nurses, but lower levels of depersonalisation. Among cancer clinicians, 'burnout' was more prevalent among clinical oncologists than among medical oncologists and palliative care specialists. Psychiatric disorder was independently associated with the stress of feeling overloaded (P < 0.0001), dealing with treatment toxicity/errors (P < 0.004) and deriving little satisfaction from professional status/esteem (P = 0.002). 'Burnout' was also related to these factors, and in addition was associated with high stress and low satisfaction from dealing with patients, and with low satisfaction from having adequate resources (each at a level of P < or = 0.002). Clinicians who felt insufficiently trained in communication and management skills had significantly higher levels of distress than those who felt sufficiently trained. If 'burnout' and psychiatric disorder among cancer clinicians are to be reduced, increased resources will be required to lessen overload and to improve training in communication and management skills.
588 citations
TL;DR: The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neurodegenerative disease, ischaemia‐reperfusion and cancer.
574 citations
472 citations
TL;DR: Its performance in the presence of noise is found to be superior to that of other blind deconvolution algorithms and the algorithm is developed further to incorporate functional forms of the point-spread function with unknown parameters.
Abstract: A blind deconvolution algorithm based on the Richardson–Lucy deconvolution algorithm is presented. Its performance in the presence of noise is found to be superior to that of other blind deconvolution algorithms. Results are presented and compared with results obtained from implementation of a Weiner filter blind deconvolution algorithm. The algorithm is developed further to incorporate functional forms of the point-spread function with unknown parameters. In the presence of noise the point-spread function can be evaluated with 1.0% error, and the object can be reconstructed with a quality near that of the deconvolution process with a known point-spread function.
469 citations
TL;DR: This article explored social class variations in choice of school in one specific locality and argued that middle-class parents are taking full advantage of "the market" to sustain or re-assert their class advantages.
Abstract: Parental choice of school is one of the main platforms of government education policy and is the centre piece of the Parents Charter. But sociological understanding of choice and choice-making is woefully underdeveloped. This paper draws on an ESRC study of market forces in education to explore social class variations in choice of school in one specific locality. The complexity of choice-making is portrayed using data from interviews with parents and it is argued that middle-class parents are taking full advantage of ‘the market’ to sustain or re-assert their class advantages.
452 citations
TL;DR: The results suggest that a signal emanating from the midline, which is absent in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6 expression in cells destined to form the optic stalks and thus may regulate the partitioning of the optic primordia into opticStalks and retinal tissue.
Abstract: Pax6 and Pax2 are members of the Pax family of transcription factors that are both expressed in the developing visual system of zebrafish embryos. Pax6 protein is present in all cells that form the neural retina and pigment epithelium, whereas Pax2 is located primarily in cells that will give rise to the optic stalk. In this study, we have addressed the role of midline signalling in the regulation of Pax2 and Pax6 distributions and in the subsequent morphogenesis of the eyes. Midline signalling is severely perturbed in cyclops mutant embryos resulting in an absence of ventral midline CNS tissue and fusion of the eyes. Mutant embryos ectopically express Pax6 in a bridge of tissue around the anterior pole of the neural keel in the position normally occupied by cells that form the optic stalks. In contrast, Pax2 protein is almost completely absent from this region in mutant embryos. Concommitant with the changes in Pax protein distribution, cells in the position of the optic stalks differentiate as retina. These results suggest that a signal emanating from the midline, which is absent in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6 expression in cells destined to form the optic stalks. Sonic hedgehog (Shh also known as Vhh-1 and Hhg-1) is a midline signalling molecule that is absent from the neuroepithelium of cyclops mutant embryos at early developmental stages. To test the possibility that Shh might be able to regulate the spatial expression of Pax6 and Pax2 in the optic primordia, it was overexpressed in the developing CNS. The number of cells containing Pax2 was increased following shh overexpression and embryos developed hypertrophied optic stalk-like structures. Complimentary to the changes in Pax2 distribution, there were fewer Pax6-containing cells and pigment epithelium and neural retina were reduced. Our results suggest that Shh or a closely related signalling molecule emanating from midline tissue in the ventral forebrain either directly or indirectly induces the expression of Pax2 and inhibits the expression of Pax6 and thus may regulate the partitioning of the optic primordia into optic stalks and retinal tissue.
449 citations
TL;DR: In this paper, the authors present some image processing techniques being developed at King's College London which, using existing closed-circuit television systems, can support both data collection and on-line monitoring of crowds.
Abstract: The understanding of crowd behaviour in semi-confined spaces is an important part of the design of new pedestrian facilities, for major layout modifications to existing areas and for the daily management of sites-subject to crowd traffic. Conventional manual measurement techniques are not suitable for comprehensive data collection of patterns of site occupation and movement. Real-time monitoring is tedious and tiring, but safety-critical. This paper presents some image processing techniques being developed at King's College London which, using existing closed-circuit television systems, can support both data collection and on-line monitoring of crowds. The application of these methods could lead to a better understanding of crowd behaviour, improved design of the built environment and increased pedestrian safety.
406 citations
TL;DR: The authors discusses some problems with the field of educational studies and considers the role of post-structuralist theory in shifting the study of education away from a technical rationalist approach towards an 'intellectual intelligence' stance that stresses contingency, disidentification and risk-taking.
Abstract: This paper discusses some problems with the field of educational studies and considers the role of post‐structuralist theory in shifting the study of education away from a ‘technical rationalist’ approach (as evidenced in the case of much research on educational management and school effectiveness) towards an ‘intellectual intelligence’ stance that stresses contingency, disidentification and risk‐taking.
TL;DR: Results suggest a requirement of shh/vhh-1 protein for the spatial regulation of nk2.2 expression in zebrafish, which is expressed in a continuous narrow band of cells along a boundary zone demarcating the location at which two of the earliest nuclei in the brain differentiate.
Abstract: We have isolated zebrafish nk2.2, a member of the Nk-2 family of homeobox genes. nk2.2 is expressed in a continuous narrow band of cells along a boundary zone demarcating the location at which two of the earliest nuclei in the brain differentiate. This band of cells is located within a few cell diameters of cells expressing the signalling molecule sonic hedgehog/vertebrate hedgehog-1 (shh/vhh-1). Injection of shh/vhh-1 RNA results in ectopic expression of nk2.2 and concomitant abnormalities in the forebrain and eyes. Moreover, cyclops mutant embryos, which initially lack neurectodermal expression of shh/vhh-1, show a concomitant lack of nk2.2 expression. Together, these results suggest a requirement of shh/vhh-1 protein for the spatial regulation of nk2.2 expression.
TL;DR: In Xenopus and zebrafish embryos expressing truncated Sek-1, lacking kinase sequences, expression of r3/r5 markers occurs in adjacent even-numbered rhombomeres, in domains contiguous with r3 or r5, suggesting a requirement for the kinase domain in the segmental restriction of gene expression.
Abstract: During development of the vertebrate hindbrain regulatory gene expression is confined to precise segmental domains. Studies of cell lineage and gene expression suggest that establishment of these domains may involve a dynamic regulation of cell identity and restriction of cell movement between segments. We have taken a dominant negative approach to interfere with the function of Sek-1, a member of the Eph-related receptor tyrosine kinase family expressed in rhombomeres r3 and r5. In Xenopus and zebrafish embryos expressing truncated Sek-1, lacking kinase sequences, expression of r3/r5 markers occurs in adjacent even-numbered rhombomeres, in domains contiguous with r3 or r5. This disruption is rescued by full-length Sek-1, indicating a requirement for the kinase domain in the segmental restriction of gene expression. These data suggest that Sek-1, perhaps with other Eph-related receptors, is required for interactions that regulate the segmental identity or movement of cells.
TL;DR: Evidence is found that allelic variation of genes which encode neurotransmitter receptors can influence clinical response to antipsychotic drugs.
TL;DR: In this article, the authors discuss the role of surface active materials, such as proteins and pentosans, in gas cell stabilisation and gas retention in whole-meal doughs, in particular the physical disruption of the foam structure by components of the outer layers of the grain.
TL;DR: A summary of the published information relating to all aspects of Quaternary travertine formation in Europe west of the Ural Mountains can be found in this paper, where the combined effects of temperature and rainfall are used to provide a zoned map showing the potential of limestones within the region.
TL;DR: It is suggested that acamprosate may reduce craving that is associated with conditioned withdrawal and be a novel kind of agent that suppresses "craving" in weaned alcohol dependent patients.
Abstract: Acamprosate is a relatively new drug that appears to be clinically useful in the treatment of alcohol dependence. Although it has proved effective in reducing relapse into drinking in clinical trials its exact mechanism of action is uncertain. Evidence is presented that the drug does not act in any of the conventional ways to reduce alcohol intake and it is proposed that it may be a novel kind of agent that suppresses "craving". On the basis of its known pharmacological effects in pre-clinical studies it is suggested that acamprosate may reduce craving that is associated with conditioned withdrawal. In addition to the potential therapeutic value of acamprosate, the drug may be useful because work directed toward understanding its mechanism of action may shed light on some of the fundamental processes that govern alcohol abuse and relapse in weaned alcohol dependent patients.
TL;DR: It is suggested that Ca2+ is required for functional changes in bull sperm, with aCa2+‐ATPase modulating intracellular Ca2 + during capacitation and calcium channels controlling the Ca2- influx required for acrosomal exocytosis.
Abstract: We have used chlortetracycline (CTC) analysis to investigate mechanisms that may play important roles during bull sperm capacitation in a culture medium (containing glucose, heparin, and caffeine) known to promote capacitation and fertilization in vitro. In initial experiments employing the Ca2+ ionophore A23187, we identified three discrete CTC patterns so similar to those described for mouse and human sperm that we have employed the same nomenclature: “F,” characteristic of uncapacitated, acrosome-intact cells; “B,” characteristic of capacitated, acrosome-intact, cells; “AR,” characteristic of capacitated, acrosome-reacted cells. Over a 60-min period, A23187 stimulated significant increases in B and AR pattern cells, with concomitant decreases in F pattern cells, suggesting a very rapid transition from the uncapacitated to the capacitated state and then on to exocytosis. Without ionophore, significant changes in the proportions of F and B pattern cells were also observed, but the maximum responses required 4 hr; the proportion of AR cells was consistently ∼ 15% throughout, indicating a low incidence of spontaneous acrosome loss. Analysis of cells in media with altered composition indicated that the inclusion of either heparin or caffeine significantly promoted capacitation to about the same extent, but together, heparin plus caffeine had an even more stimulatory effect. Despite this, none of these treatments triggered acrosome loss above the levels seen in media lacking these constituents. In the presence of caffeine, with or without heparin, the inclusion of glucose had little effect on responses, but in the presence of heparin there were fewer B cells. In the presence of either quercetin, a Ca-ATPase inhibitor used at 50–200 μM, or W-7, a calmodulin antagonist used at 5–125 μM, capacitation per se was accelerated, as evidenced by significant decreases in F and significant increases in B pattern cells; only the highest concentration of each caused significant increases in AR cells. In addition, 25 and 125 μM W-7 markedly stimulated motility, both quantitatively and qualitatively. Finally the Na+ ionophore monensin at 500 μM significantly accelerated both capacitation and acrosomal exocytosis. The addition of the dihydropyridine calcium channel blocker nifedipine at 10 nM, just prior to monensin, did not inhibit capacitation (F to B transition) but blocked acrosomal exocytosis (B to AR transition). We suggest that Ca2+ is required for functional changes in bull sperm, with a Ca2+-ATPase modulating intracellular Ca2+ during capacitation and calcium channels controlling the Ca2+ influx required for acrosomal exocytosis. © 1995 Wiley-Liss, Inc.
TL;DR: It is concluded that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA and not cell‐specific factors, as previously concluded.
Abstract: We have analysed the endogenous retinoids present in whole mouse embryos from day 9 to day 14 of development and in individual components of the embryo at two stages, day 10.5 and day 13, by HPLC. We can only detect two retinoids, all-trans-RA (tRA) and all-trans-retinol (t-retinol), and t-retinol is 5-10-fold in excess over tRA. We cannot detect 9-cis-RA or any didehydroretinoids; thus mammalian embryos seem to differ in their retinoid content from other embryos such as chick, Xenopus, and fish. The levels of tRA do not change significantly over the 6 days of development analysed, whereas t-retinol rises sharply as the liver develops. Within the embryo, tRA is present at high levels in the developing spinal cord and at very low levels in the forebrain; indeed there is a gradient of endogenous tRA from the forebrain to the spinal cord. Other parts of the embryo had intermediate levels of tRA. When a teratogenic dose of RA was administered to day 10.5 embryos, the levels of tRA present in individual tissues of the embryo rose dramatically--from 175-fold to 1,400-fold--and the levels rose in all tissues not in any exclusive areas. We then determined which areas of the embryo were malformed by such a teratogenic dose. The lower jaw, palate, vertebrae, tail, and limbs were consistently abnormal, and since these areas received a dose of tRA no higher than any other it was concluded that cell-specific factors must determine the teratogenic response of these tissues. We then considered whether cellular retinoic acid-binding protein I or II (CRABP I or II) played any role in this response by determining their relative levels in each of the tissues analysed. There was no correlation between the presence of CRABP I and II and the distribution of administered RA. Neither was there a clear correlation in detail between the presence of CRABP I and II and the sites of teratogenesis. We therefore conclude that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA.
TL;DR: It is suggested that the germ ring acts as a posteriorising centre during AP patterning, mediated by FGF activity in this tissue, where these genes, and ntl, are expressed.
Abstract: To analyse the roles of FGF activity and brachyury during gastrulation we have directly compared the consequences of inhibition of FGF-receptor signalling with the phenotype of the zebrafish brachyury mutant, no tail (ntl). We show that expression of ntl is regulated by FGF and that inhibition of FGF receptor-signalling leads to complete loss of the trunk and tail. Since the ntl mutant lacks the tail and notochord but has an otherwise normal trunk, this demonstrates that trunk development is dependent upon an unidentified gene, or set of genes, referred to as no trunk (ntk) which is regulated by FGF. We propose a model to explain the FGF-dependent regulation of ntl and ntk that accounts for the above phenotypes. Consistent with this model, over-expression of eFGF led to suppression of anterior fates and development of trunk and tail derivatives only. In addition, widespread activation of convergence and extension movements resulted in the formation of multiple axis-like structures. Expression of eve1 and cad1 was also regulated by FGF activity, suggesting that during gastrulation FGF activity is normally restricted to the germ ring where these genes, and ntl, are expressed. Taken together these data suggest that the germ ring acts as a posteriorising centre during AP patterning, mediated by FGF activity in this tissue.
TL;DR: The MPTP‐treated marmoset provides a useful model in which to study dyskinesias in Parkinson's disease and to examine new therapeutic strategies aimed at alleviating this common side effect of chronic dopamine replacement therapy.
Abstract: Dyskinesias occur in the majority of patients with Parkinson's disease chronically treated with L-DOPA and also occur in several nonhuman primate species after 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) and L-DOPA treatment. The common marmoset (Callithrix jacchus) shows parkinsonian motor deficits after MPTP administration, and we now report dyskinesias occurring in this species during chronic L-DOPA exposure. Marmosets rendered chronically parkinsonian after MPTP administration were treated orally with L-DOPA plus carbidopa for 3 weeks. After several days the animals began to display chorea, choreoathetosis, and dystonia. The severity of dyskinesias varied between the animals, with the most severely parkinsonian animals displaying the most dyskinetic movements. Each animal showed an idiosyncratic pattern of dyskinesias, which was highly reproducible. These L-DOPA-primed animals also received other D2 D1, and mixed D1/D2 agonist drugs. Quinpirole, bromocriptine, pergolide, apomorphine, and A-77636 all produce dyskinesias that were identical in character to those seen after L-DOPA administration, but the D1 agonist A-77636 gradually abolished dyskinesias while preserving its antiparkinsonian activity. The MPTP-treated marmoset provides a useful model in which to study dyskinesias in Parkinson's disease and to examine new therapeutic strategies aimed at alleviating this common side effect of chronic dopamine replacement therapy.
TL;DR: The dipeptide carnosine (β‐alanyl‐l‐histidine) was readily glycosylated non‐enzymatically upon incubation with the sugars glucose, galactose, deoxyribose and the triose dihydroxyacetone and it protected α‐crystallin, superoxide dismutase and catalise against glycation and cross‐linking mediated by ribose, of course.
TL;DR: Plants used in traditional medicine have an important role to play in the maintenance of health in all parts of the world and in the introduction of new treatments.
Abstract: Recent years have witnessed a renewed interest in plants as pharmaceuticals in the Western world. This interest is channeled into the discovery of new biologically-active molecules by the pharmaceutical industry and into the adoption of crude extracts of plants for self-medication by the general public. In both of these areas some attention is being paid to the investigation and use of ethnopharmacology, the traditional use of plants for medicinal purposes by particular cultural groups. Ethnopharmacologic leads have resulted in the introduction of new single molecule drugs but have a greater role to play if crude extracts are accepted for clinical use in the West. The problems confronting such usage are discussed. Considerable benefits for developing countries are possible when the local medicinal plants are subjected to scientific methods of validation of traditional use and quality control. This approach has met with success in some parts of the world but is not always appreciated by national government...
TL;DR: In this paper, the effects of vegetation change on interrill runoff and erosion are investigated by performing field experiments on small and large runoff plots located on contemporary grassland and shrubland hillslopes in Walnut Gulch Experimental Watershed.
TL;DR: This study supports the use of tea‐tree oil in the treatment of acne, and demonstrates that terpinen‐4‐ol is not the sole active constituent of the oil.
Abstract: Major components of two tea-tree oil samples were identified using thin layer and gas-liquid chromatography (TLC and GLC). Using a TLC-bioautographic technique, the tea-tree oils, terpinen-4-ol, alpha-terpineol and alpha-pinene were found to be active against Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes whereas cineole was inactive against these organisms. The MIC values of the three active compounds increased in the order alpha-terpineol < terpinen-4-ol < alpha-pinene for all three micro-organisms. MIC values of the tea-tree oils and terpinen-4-ol were lower for P. acnes than for the two staphylococci. This study supports the use of tea-tree oil in the treatment of acne, and demonstrates that terpinen-4-ol is not the sole active constituent of the oil.
29 May 1995
TL;DR: In this paper, it was shown that a unit-cost RAM with a word length of bits can sort integers in the range in time, for arbitrary!, a significant improvement over the bound of " # $ achieved by the fusion trees of Fredman and Willard, provided that % &'( *),+., for some fixed /102, the sorting can even be accomplished in linear expected time with a randomized algorithm.
Abstract: We show that a unit-cost RAM with a word length of bits can sort integers in the range in time, for arbitrary ! , a significant improvement over the bound of " # $ achieved by the fusion trees of Fredman and Willard. Provided that % & ' ( *),+., for some fixed /102 , the sorting can even be accomplished in linear expected time with a randomized algorithm. Both of our algorithms parallelize without loss on a unitcost PRAM with a word length of bits. The first one yields an algorithm that uses 3 4 5 $ time and 6 ( operations on a deterministic CRCW PRAM. The second one yields an algorithm that uses ' 5 7 expected time and " expected operations on a randomized EREW PRAM, provided that 8 ' 5 7 *),+.for some fixed /90: . Our deterministic and randomized sequential and parallel algorithms generalize to the lexicographic sorting problem of sorting multiple-precision integers represented in several words.
TL;DR: Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most successful group of drugs ever marketed, which demonstrates their overall efficacy, but they are not, however, without side effects.
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most successful group of drugs ever marketed, which demonstrates their overall efficacy. They are not, however, without side effects (...
TL;DR: The results indicate that the 5-HT2C receptor may contain the major site of action through which clozapine mediates its antipsychotic effects.
Abstract: A cysteine to serine substitution at amino acid 23 in the 5-HT 2C receptor gene alters the pharmacological properties of the protein. We investigated this polymorphism in subjects with schizophrenia resistant to conventional neuroleptic drugs, and analysed our data for allelic association between the disease state or clinical response to the atypical antipsychotic drug, clozapine. Ninety percent of subjects who had one or more 5-HT 2C ser alleles (19/21) were classified as clozapine responders compared with 59% (84/141) without this allele (χ 2 = 7.7, p = 0.005), suggesting that this mutation is a predictor of good response to clozapine. There was no association between schizophrenia and the 5-HT 2C ser allele, but our results indicate that the 5-HT 2C receptor may contain the major site of action through which clozapine mediates its antipsychotic effects.
TL;DR: The light-chain region of the myosin head tilts both during the imposed filament sliding and during the subsequent quick force recovery that is thought to signal the elementary force-generating event.
Abstract: Force generation and relative sliding between the myosin and actin filaments in muscle are thought to be caused by tilting of the head region of the myosin crossbridges between the filaments. Structural and spectroscopic experiments have demonstrated segmental flexibility of myosin in muscle, but have not shown a direct linkage between tilting of the myosin heads and either force generation or filament sliding. Here we use fluorescence polarization to detect changes in the orientation of the light-chain region of the head, the part most likely to tilt, and synchronized head movements by imposing rapid length steps. We found that the light-chain region of the myosin head tilts both during the imposed filament sliding and during the subsequent quick force recovery that is thought to signal the elementary force-generating event.
TL;DR: Interest in the role of free radicals in rheumatoid arthritis (RA) stems from the seminal work of McCord,' who noted the decreased viscosity of synovial fluid in RA patients and showed that a similar decrease could be produced by exposing synovials to a system generating superoxide radical.
Abstract: Interest in the role of free radicals in rheumatoid arthritis (RA) stems from the seminal work of McCord,' who noted the decreased viscosity of synovial fluid in RA patients and showed that a similar decrease could be produced by exposing synovial fluid, or solutions of hyaluronic acid, to a system generating superoxide radical, 02-. McCord's observations led to interest in the use of intraarticular injections of the antioxidant enzyme superoxide dismutase as a treatment in RA. However, the clinical data presented did not convince many rheumatologists2 3 and overenthusiastic interpretations of the data may have led to unwarranted scepticism about the real role of free radicals in RA. Let us review our current knowledge.