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At least 757 records · Page 42Linked to original sources

PubMed2003

Exploring the patient's experiences of learning to live with an implantable cardioverter defibrillator (ICD) from one UK centre: a qualitative study.

BACKGROUND: International expansion of indications for implantable cardioverter defibrillator (ICD) implant means increasing numbers of patients with devices worldwide. However, smaller numbers of patients with ICDs in the UK has meant that clinical expertise available to care for this specialized group is limited. Whilst North American patients' experiences of living with an ICD are well documented, European perspectives remain underrepresented. AIM: The aim of this study was to explore and describe patient's experiences around the time of their ICD device implant and after they returned home from one UK centre. METHODS AND RESULTS: Eligible patients were recruited from one regional cardiothoracic centre and interviewed in their own homes using semi-structured schedules. Analysis of data elicited three themes; non-individualised nature of information, adjustments to living with the device and future outlook. Unique findings identified were; (a) concealment of concerns and symptoms; (b) funding issues; and (c) unavailability of appropriate support and advice during and after time in hospital. CONCLUSION: Individualized care and support for these ICD patients appeared lacking according to respondents. Opportunities to discuss concerns appeared non-existent, which may indicate that UK patients are disadvantaged in the domain of psychological support compared with their European and North American counterparts. Findings remain tentative until explored with a larger, more representative and international sample.

Activities of Daily Living↗

PubMed1999

Limitations of imaging for foreign bodies in parapharyngeal abscess and the importance of surgical exploration.

A rare cause of parapharyngeal abscess in association with a wooden skewer is presented. Despite the use of both ultrasound and computed tomography (CT) scanning as diagnostic tools, the foreign body could not be identified. Only through a meticulous exploration of the neck was the foreign body located. The importance of surgical exploration even with negative imaging is discussed.

Abscess↗

PubMed2002

Protein conformations explored by difference high-angle solution X-ray scattering: oxidation state and temperature dependent changes in cytochrome C.

We demonstrate the use of high-angle X-ray scattering to explore protein conformational states in solution by resolving oxidation state- and temperature-dependent changes in the conformation of horse heart cytochrome c. Several detailed models exist for oxidation-dependent changes in mitochondrial class I c cytochromes determined by X-ray crystallography and solution NMR techniques. These models differ in the magnitude and locations of structural change. Our scattering measurements show that high-angle X-ray scattering can discriminate between these models, and that the experimental scattering data for horse cytochrome c can be best reconciled with selected NMR models for the same protein. These results demonstrate the ability to use high-angle X-ray scattering to resolve conformational states of proteins in solution, and to relate these measurements to detailed structural models. Furthermore, temperature-dependent changes are found in the high angle scattering patterns for horse cytochrome c, illustrating the sensitivity of these measurements to dynamic aspects of protein structure. These results demonstrate the ability to use difference high angle scattering as a quantitative monitor of reaction-linked changes in protein conformation and structural dynamics. Synchrotron-based high-angle scattering holds promise as a widely applicable, high throughput technique for exploring conformational states linked to physiological protein function, for resolving configurational differences between protein structures in solution and crystalline states, and for bridging the gap between solution NMR and crystallographic structure techniques.

Animals↗

PubMed2005

Exploring the mechanism of binding of UDP-galactopyranose to UDP-galactopyranose mutase by STD-NMR spectroscopy and molecular modeling.

UDP-galactopyranose mutase (UGM) is the key enzyme involved in the biosynthesis of Galf. In this study, reliable structural binding modes of the natural substrate, UDP-Galp, and inhibitor, UDP, in the UGM active site were provided with the combined use of STD-NMR spectroscopy, molecular modeling, and CORCEMA-ST calculations. UDP-Galp and UDP exhibited similar binding epitopes recognized by UGM. However, the relative binding affinities of the ligands changed dramatically upon reduction of UGM, as explored by competitive STD-NMR experiments. UDP-Galp competes with UDP for binding to UGM, especially when UGM is in its reduced state. Docking studies for predicting the binding mode within the active site of the two monomers in UGM explored the possibility that the mobile loop might act as a gateway for substrate binding, and the structure of the binding cleft in monomer A might be a closer approximation of the substrate-bound active site than monomer B. Important information regarding the critical interactions of UGM with UDP-Galp has been obtained.

Binding Sites↗

PubMed2006

A multifactor exploration of the photobleaching of Suwannee River dissolved organic matter across the freshwater/saltwater interface.

A four factor central composite experimental design was applied to explore the photobleaching of Suwannee River dissolved organic matter (SRDOM) at 350 nm as a function of the tetravariate system of [SRDOM], total [Fe(III)], [NO3-], and salinity. The ranges of each factor were setto cover their likely concentrations atthe freshwater/ saltwater interface, to encompass the possible conditions encountered during the transition from the terrestrial to marine environment. Each experiment was carried out using a minimum of 25 different initial conditions, with 3-6 replicates/condition. The resulting data set mapped out the effects of multiple photoactive components on the rate of photobleaching. Under the conditions tested (nominally total [Fe(III)] 0.00-4.00 microM; [NO3-] 0.00-60.00 microM; SRDOM 0.00-30.00 mg/L; salinity 0.00-35.00 ppt, polychromatic illumination, pH 8.2) all samples photobleached at all wavelengths measured, and the absorption at 350 nm bleached the most rapidly. The most important factor for predicting the rate of photobleaching at 350 nm was the initial loading of SRDOM; the effect of all other factors on photobleaching was not significant at the 95% level of confidence. Varied salinity, Fe(III), or added D2O had no effect on the rate of photobleaching, indicating that hydroxyl radical, singlet oxygen, and superoxide did not contribute significantly to the loss of the chromophore at 350 nm. The addition of hydroquinone or thiosulfate inhibited photobleaching, suggesting photobleaching may depend on a weaker oxidant such as the excited-state acceptors (derived from SRDOM directly) produced during photoinitiated charge-transfer processes. The advantages of multifactor experimental techniques for exploring SRDOM photochemistry are discussed.

Ferric Compounds↗

PubMed2006

Conformationally constrained analogues of diacylglycerol. 26. Exploring the chemical space surrounding the C1 domain of protein kinase C with DAG-lactones containing aryl groups at the sn-1 and sn-2 positions.

Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by the different cellular scaffolds, the lipid composition of the specific membranes, and the targeting information intrinsic to the individual isoforms bound to DAG. This multifaceted control of diversity suggests that, to develop effective DAG-lactones capable of honing in on a specific cellular target, we need to gain a better understanding of the chemical space surrounding its binding site. Seeking to augment the chemical repertoire of DAG-lactone side chains that could steer the translocation of PKC to specific cellular domains, we report herein the effects of incorporating simple or substituted phenyl residues. A combined series of n-alkyl and phenyl substitutions were used to explore the optimal location of the phenyl group on the side chains. The substantial differences in binding affinity between DAG-lactones with identical functionalized phenyl groups at either the sn-1 or sn-2 position are consistent with the proposed binding model in which the DAG-lactone binds to the C1 domain of PKC with the acyl chain oriented toward the interior of the membrane and the alpha-alkylidene or alpha-arylalkylidene chains directed to the surface of the C1 domain adjacent to the lipid interface. We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity.

Diglycerides↗

PubMed1999

Exploring the structure-activity relationships of [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), a high-affinity and selective delta-opioid receptor nonpeptide agonist ligand.

SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the delta-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation.(6) To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH(2)-O-CH(2)-Ph; b = Me; c = CH(2)Ph; d = CH(2)OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the delta-receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.

Animals↗

PubMed2000

3D-QSAR CoMFA study on imidazolinergic I(2) ligands: a significant model through a combined exploration of structural diversity and methodology.

Displaying an unprecedented structural diversity, 119 I(2) ligands, and their pK(i) values, were collected and submitted to a comparative molecular fields analysis (CoMFA) study. They were discerned into three structural subsets (A, B, C), to explore the I(2) 3D-QSARs from finite structural systems (A, B, C) to more complex ones (AB, AC, BC, ABC). In addition, various key steps of the CoMFA methology were explored. The applied method used two pharmacophore templates and seven molecular field combinations (electrostatic, lipophilic, steric), as well as eight alignment methods (two point-by-point and six similarity-based variations). That way, 644 CoMFA models were obtained and further selected according to their predictive ability through two filters. The first filter was mainly based on the q(2), which internally evaluates the predictive ability from the training set. For the second filter, the predictive ability was externally evaluated through the prediction of test sets. Finally, one model was extracted from the whole data as the best. Indeed, it combines three features of upmost importance for the further design of ligands endowed with high I(2) affinity: structural diversity (n = 73), robustness (N = 9, r(2) = 0.96, s = 0. 28, F = 148), and a great fully assessed predictive ability (q(2) = 0.50, r(2)(test set) = 0.81, n(test set) = 46). On the basis of structural data and CoMFA isocontours, some elements of the I(2) tridimensional pharmacophore are also suggested.

Drug Design↗

PubMed2006

Excited-state dynamics of carotenoids in light-harvesting complexes. 1. Exploring the relationship between the S1 and S* states.

Dispersed transient absorption spectra collected at variable excitation intensities in combination with time-resolved signals were used to explore the underlying connectivity of the electronic excited-state manifold of the carotenoid rhodopin glucoside in the light-harvesting 2 complex isolated from Rhodopseudomonas acidophila. We find that the S state, which was recently identified as an excited state in carotenoids bound in bacterial light-harvesting complexes, exhibits a different response to the increase of excitation intensity than the S(1) state, which suggests that the models used so far to describe the excited states of carotenoids are incomplete. We propose two new models that can describe both the time-resolved and the intensity-dependent data; the first postulates that S(1) and S* are not populated in parallel after the decay of the initially excited S(2) state but instead result from the excitation of distinct ground-state subpopulations. The second model introduces a resonantly enhanced light-induced transition during excitation, which promotes population to higher-lying excited states that favors the formation of S* over S(1). Multiwavelength target analysis of the time-resolved and excitation-intensity dependence measurements were used to characterize the involved states and their responses. We show that both proposed models adequately fit the measured data, although it is not possible to determine which model is most apt. The physical origins and implications of both models are explored.

Antioxidants↗

PubMed2006

Exploring the interaction of ruthenium(II) polypyridyl complexes with DNA using single-molecule techniques.

Here we explore DNA binding by a family of ruthenium(II) polypyridyl complexes using an atomic force microscope (AFM) and optical tweezers. We demonstrate using AFM that Ru(bpy)2dppz2+ intercalates into DNA (K(b) = 1.5 x 10(5) M(-1)), as does its close relative Ru(bpy)2dppx2+ (K(b) = 1.5 x 10(5) M(-1)). However, intercalation by Ru(phen)3(2+) and other Ru(II) complexes with K(b) values lower than that of Ru(bpy)2dppz2+ is difficult to determine using AFM because of competing aggregation and surface-binding phenomena. At the high Ru(II) concentrations required to evaluate intercalation, most of the DNA strands acquire a twisted, curled conformation that is impossible to measure accurately. The condensation of DNA on mica in the presence of polycations is well known, but it clearly precludes the accurate assessment by AFM of DNA intercalation by most Ru(II) complexes, though not by ethidium bromide and other monovalent intercalators. When stretching individual DNA molecules using optical tweezers, the same limitation on high metal concentration does not exist. Using optical tweezers, we show that Ru(phen)2dppz2+ intercalates avidly (K(b) = 3.2 x 10(6) M(-1)) whereas Ru(bpy)3(2+) does not intercalate, even at micromolar ruthenium concentrations. Ru(phen)3(2+) is shown to intercalate weakly (i.e., at micromolar concentrations (K(b) = 8.8 x 10(3) M(-1))). The distinct differences in DNA stretching behavior between Ru(phen)3(2+) and Ru(bpy)3(2+) clearly illustrate that intercalation can be distinguished from groove binding by pulling the DNA with optical tweezers. Our results demonstrate both the benefits and challenges of two single-molecule methods of exploring DNA binding and help to elucidate the mode of binding of Ru(phen)3(2+).

DNA↗

PubMed2004

Am I a carer and do I care? An exploration of the concept of care as applied to osteopathic practice.

A number of dichotomies bedevil the concept of care, among them, the question of whether healthcare is posited on care or cure. On one side the question is whether it is enough to cure without caring (to cure is to care) and on the other whether caring is sufficient without a cure. This has received attention in recent years from feminists, particularly in the nursing profession, and from renewed interest in virtue ethics. This paper describes a study that was undertaken to explore what a group of experienced United Kingdom based osteopaths understand care to be. Following interviews and transcript analysis using Grounded Theory, a number of themes were identified: Care as communication; Care as understanding the patient; Care as the therapeutic relationship; Care as action; Care as most beneficial outcome. The relationships between the various themes were explored and a 'model of osteopathic care' was proposed. Most of the respondents put beneficial outcome of some kind at the heart of their understanding but the process of caring was not regarded as particularly important on its own. In fact the expressed intention of osteopathic care was to facilitate a beneficial outcome. However, beneficial outcome was described in very broad terms and was not confined to the resolution of patients' presenting symptoms. In placing beneficial outcome at the heart of their model of care, respondents did not appear to recognize the dichotomy between care and cure, a finding that contrasts sharply with a number of nursing studies. The paper concludes by suggesting how it may be possible to differentiate between care and good practice.

Caregivers↗

PubMed2004

Raman spectroscopic protocol for the molecular recognition of key biomarkers in astrobiological exploration.

Raman spectroscopy is proposed as novel instrumentation for the remote, robotic exploration of planetary surfaces, especially Mars. In recent years, information about the chemicals produced by organisms at the terrestrial limits of life, such as those surviving in Antarctic habitats, has facilitated the assembly of a spectral database of key biomarkers. In addition biogeological modifications which are essential for the survival strategies of environmentally stressed organisms have been identified. In this paper, the requirements for Raman spectroscopic instrumental detection of key bio--and bio-geological markers are outlined and a preliminary protocol established for the molecular spectral recognition of biological signatures in remote astrobiological exploration.

Biomarkers↗

PubMed1999

Exploring for a record of ancient Martian life.

The immediate task facing exopaleontology is to define a strategy to explore Mars for a fossil record during the decade-long exploration program that lies ahead. Consideration of the quality of paleontological information preserved under different geological conditions is important if we are to develop a strategy with broad applicability. The preservation of microbial fossils is strongly influenced by the physical, chemical, and biological factors of the environment which, acting together, determine the types of information that will be captured and retained in the rock record. In detrital sedimentary systems, preservation is favored by rapid burial in fine-grained, clay-rich sediments. In chemical sedimentary systems, preservation is enhanced by rapid entombment in fine-grained chemical precipitates. For long-term preservation, host rocks must be composed of stable minerals that are resistant to chemical weathering and that form an impermeable matrix and closed chemical system to protect biosignatures from alteration during subsequent diagenesis or metamorphism. In this context, host rocks composed of highly ordered, chemically stable mineral phases, like silica (e.g., cherts) or phosphate (e.g., phosphorites), are especially favored. Such lithologies tend to have very long crustal residence times and, along with carbonates and shales, are the most common host rocks for the Precambrian microfossil record on Earth. Although we make the defensible assumption that Mars was more like the Earth early in its history, clearly, the geological and historical differences between the two planets are many. Such differences must be carefully considered when adapting an Earth-based strategy to Mars.

Carbonates↗

PubMed1999

A Mossbauer investigation of iron-rich terrestrial hydrothermal vent systems: lessons for Mars exploration.

Hydrothermal spring systems may well have been present on early Mars and could have served as a habitat for primitive life. The integrated instrument suite of the Athena Rover has, as a component on the robotic arm, a Mossbauer spectrometer. In the context of future Mars exploration we present results of Mossbauer analysis of a suite of samples from an iron-rich thermal spring in the Chocolate Pots area of Yellowstone National Park (YNP) and from Obsidian Pool (YNP) and Manitou Springs, Colorado. We have found that Mossbauer spectroscopy can discriminate among the iron-bearing minerals in our samples. Those near the vent and on the surface are identified as ferrihydrite, an amorphous ferric mineraloid. Subsurface samples, collected from cores, which are likely to have undergone inorganic and/or biologically mediated alteration (diagenesis), exhibit spectral signatures that include nontronite (a smectite clay), hematite (alpha-Fe2O3), small-particle/nanophase goethite (alpha-FeOOH), and siderite (FeCO3). We find for iron minerals that Mossbauer spectroscopy is at least as efficient in identification as X-ray diffraction. This observation is important from an exploration standpoint. As a planetary surface instrument, Mossbauer spectroscopy can yield high-quality spectral data without sample preparation (backscatter mode). We have also used field emission scanning electron microscopy (FESEM), in conjunction with energy-dispersive X ray (EDX) fluorescence spectroscopy, to characterize the microbiological component of surface sinters and the relation between the microbiological and the mineralogical framework. Evidence is presented that the minerals found in these deposits can have multi-billion-year residence times and thus may have survived their possible production in a putative early Martian hot spring up to the present day. Examples include the nanophase property and the Mossbauer signature for siderite, which has been identified in a 2.09-billion-year old hematite-rich chert stromatolite. Our research demonstrates that in situ Mossbauer spectroscopy can help determine whether hydrothermal mineral deposits exist on Mars, which is significant for exobiology because of the issue of whether that world ever had conditions conductive to the origin of life. As a useful tool for selection of samples suitable for transport to Earth, Mossbauer spectroscopy will not only serve geological interests but will also have potential for exopaleontology.

Colorado↗

PubMed1993

Haptic exploration in the presence of vision.

Two experiments addressed initiation of haptic exploration to encode object properties when vision is present. Ss compared pairs of objects on designated properties, using only vision or with touch permitted. Tough initiation, reach, contact, and visual responses were timed. With difficult material judgments, tough occurred frequently and was initiated faster than the time to respond by vision alone. With geometric judgments, touch was rarely used and then was initiated at the typical time for a visual response. Imposing a visual preview before allowing touch did not reduce the incidence of touch but did speed its initiation. Results support a model in which preliminary visual processing quickly initiates haptic exploration for material judgments that are visually or semantically difficult.

Adult↗

PubMed1991

Imagined haptic exploration in judgments of object properties.

In Experiment 1, each subject rated a single, named object for its roughness, hardness, temperature, weight, size, or shape. In Experiment 2, each subject compared one pair of objects along the same dimensions. In both studies, a substantial proportion of subjects who judged the first four dimensions imagined a hand making exploratory movements appropriate for the designated information. The proportion of hand-exploration images decreased substantially when judging size or shape, or when judgments could be made readily through general semantic knowledge. The results suggest that the incorporation of haptic exploration into visual imagery provides access to information about haptically accessible object properties.

Adult↗

PubMed1989

Object exploration, habituation, and response to a spatial change in rats following septal or medial frontal cortical damage.

Normal rats and rats sustaining septal or medial frontal cortex lesions were compared in experiments dealing with object exploration, habituation, and reaction to novelty (measured by renewed exploration following a spatial change). Normal rats exhibited high levels of initial exploratory activity which decreased over time. Following a spatial change, they reinvestigated both the displaced object and the nondisplaced ones. Frontal animals were similar to normal subjects with respect to their initial exploratory level and habituation pattern. However, frontal rats reexplored only the displaced object and completely neglected the nondisplaced ones. In contrast, the behavioral pattern displayed by septal rats was markedly different from that of normal and frontal animals. Septal rats had lower levels of initial exploratory activity, did not habituate over time, and failed to react to either displaced or nondisplaced objects. These results show that although the septo-hippocampal complex and the medial frontal cortex may share some common function in spatially organized behaviors, both structures have unique roles. Some hypotheses about the possible basic processes subtended by the septal area or the medial frontal cortex are briefly mentioned and discussed.

Animals↗

PubMed1989

2-[3H]deoxyglucose uptake patterns in rats exploring a six-arm radial tunnel maze: differences between experienced and nonexperienced rats.

In an automated tunnel maze, rats were allowed to explore either a 6-arm radial configuration ("experienced") or an alley maze configuration ("nonexperienced"). The activity of control rats was restricted to the center of the maze. After 8 daily sessions and a 5-day break, catheters were implanted into the jugular vein. Two days later, 2-deoxyglucose was administered before both experimental groups were exposed to the 6-arm radial configuration. Nonexperienced rats differed from experienced rats in terms of efficiency of exploration, but not in locomotor activity. Compared with experienced animals, nonexperienced rats showed an increase in 2-deoxyglucose uptake in prefrontal and cingulate cortices and in mediodorsal and laterodorsal thalamic nuclei. Exposure of rats to familiar and unfamiliar maze patterns resulted in different patterns of brain metabolic activity.

Animals↗