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At least 415 records · Page 23Linked to original sources
PubMed1998

Neural correlates of visual and motor decision processes.

Recent research has clarified and revealed characteristics of perceptual and motor decision processes in the brain. A democracy of sensory neurons discriminate the properties of a stimulus, while competition contrasts the attributes of stimuli across the visual field to locate conspicuous stimuli. Salience and significance are weighed to select an object on which to focus attention and action. Experimentally combining neural and mental chronometry has determined the contribution of perceptual and motor processes to the duration and variability of behavioral reaction time. Whereas perceptual processing occupies a relatively constant amount of time for a given stimulus condition, the processes of mapping particular stimuli onto the appropriate behavior and preparing the motor response provide flexibility but introduce delay and variability in reaction time.

Animals↗
PubMedDate not supplied

Integrated case management: the 21st century challenge for HMO case managers: Part I.

As HMOs approach the new millennium, their care and cost management strategies still will be under attack by policy-makers, legislative bodies, the media, American businesses, and the medical professions. The HMO industry will continue to be held accountable for the efficiency of its services, the quality of its care, and the performance and outcome measures that are the results of managing both the care and medical costs of its membership. This first of a two-part series put forward the concept of an integrated CM model to manage the total care of needs of HMO members at the turn of the century. This model consists of three care management approaches commonly used in mature HMOs: demand management, CM, and DM, as illustrated in Figure 1 and defined in Table 1. This article also described the new challenges facing HMOs, physicians, and nurse case managers and how they are navigating the difficult process of mapping demand management and CM approaches to the medical, social, and environmental needs of HMO members. With the costs of chronic conditions consuming 61% of the nation's annual health bill and increased numbers of the elderly joining HMOs, HMOs strongly need to implement DM approaches for economic survival reasons alone. Part two of this series will focus on the newest care management approach: disease state management.

Case Management↗
PubMed2003

Reading maps of the genes: interpreting the spatiality of genetic knowledge.

Genetics has become the pre-eminent interpretation of the body and health and illness. This paper engages with a central technique and metaphor of the new genetics-gene mapping. Through an exploration of the process of gene mapping, the paper argues that the genetic material of the body is spatialised and transformed into a knowable and manipulable entity. Three interpretations of this spatial transformation of the body's materiality are discussed, in turn drawing on Foucault's notion of the construction of medical knowledge, the deconstruction of geographical maps and Haraway's 'fetishised' conception of the gene map. The paper concludes by considering contestations to this dominant discourse, and begins to construct an alternative spatialisation of the body that attempts to 'place' the gene more appropriately in a socially-embedded body and health.

Chromosome Mapping↗
PubMedDate not supplied

Flux balance analysis of photoautotrophic metabolism.

Photosynthesis is the principal process responsible for fixation of inorganic carbon dioxide into organic molecules with sunlight as the energy source. Potentially, many chemicals could be inexpensively produced by photosynthetic organisms. Mathematical modeling of photoautotrophic metabolism is therefore important to evaluate maximum theoretical product yields and to deeply understand the interactions between biochemical energy, carbon fixation, and assimilation pathways. Flux balance analysis based on linear programming is applied to photoautotrophic metabolism. The stoichiometric network of a model photosynthetic prokaryote, Synechocystis sp. PCC 6803, has been reconstructed from genomic data and biochemical literature and coupled with a model of the photophosphorylation processes. Flux map topologies for the hetero-, auto-, and mixotrophic modes of metabolism under conditions of optimal growth were determined and compared. The roles of important metabolic reactions such as the glyoxylate shunt and the transhydrogenase reaction were analyzed. We also theoretically evaluated the effect of gene deletions or additions on biomass yield and metabolic flux distributions.

Biomass↗
PubMed2006

Low-dimensional manifolds in reaction-diffusion equations. 1. Fundamental aspects.

The approach to equilibrium for systems of reaction-diffusion equations on bounded domains is studied geometrically. It is shown that equilibrium is approached via low-dimensional manifolds in the infinite-dimensional function space for these dissipative, parabolic systems. The fundamental aspects of this process are mapped out in some detail for single species cases and for two-species cases where there is an exact solution. It is shown how the manifolds reduce the dimensionality of the system from infinite dimensions to only a few dimensions.

Journal Article↗
PubMedDate not supplied

Multiple functional categories of proteins identified in an in vitro cellular ubiquitin affinity extract using shotgun peptide sequencing.

To construct a high information content assay for examination of the function of the cellular ubiquitin system, we added his-tagged ubiquitin, ATP, and an ATP-regenerating system to endogenous human cellular ubiquitin system enzymes, and labeled cellular proteins with hexa-histidine tagged ubiquitin in vitro. Labeling depended on ATP, the ATP recycling system, the proteasome inhibitor MG132, and the ubiquitin protease inhibitor ubiquitin aldehyde, and was inhibited by iodoacetamide. Quadruplicate affinity extracted proteins were digested with trypsin, and the peptides were analyzed by 2D capillary LC-MS/MS, SEQUEST, MEDUSA, and support vector machine calculations. Identified proteins included 22 proteasome subunits or associated proteins, 18 E1, E2, or E3 ubiquitin system enzymes or related proteins, 4 ubiquitin domain proteins and 36 proteins in functional clusters associated with redox processes, endocytosis/vesicle trafficking, the cytoskeleton, DNA damage/repair, calcium binding, and mRNA splicing. This suggests a link between the ubiquitin system and these cellular processes. This map of cellular ubiquitin-associated proteins may be useful for further studies of ubiquitin system function.

Algorithms↗
PubMed1988

Understanding the central processing limit in consistent-mapping visual search tasks.

Effects of load (i.e., the number of stimuli in the display) have been observed in multiple-frame studies using a consistent mapping of stimuli to responses (e.g., Fisher, 1982, 1984). In a series of four experiments, it is shown that these effects are not the consequence of differences across the high- and low-load conditions in either decision noise or peripheral masking. Additionally, it is shown that of two modes of limited capacity (a limited-channel and divided-capacity model) considered as possible explanations of load effects in tasks where subjects are required to locate a target, only one--the limited-channel model--is consistent with the results from all three location tasks. Finally, it is argued that the limited-channel model predicts not only the behavior observed in the four consistent-mapping experiments reported in this article but also the behavior observed in several related consistent-mapping tasks (Kleiss & Lane, 1986; Shiffrin & Gardner, 1972).

Attention↗
PubMed1998

Gene transfer to the nucleus and the evolution of chloroplasts.

Photosynthetic eukaryotes, particularly unicellular forms, possess a fossil record that is either wrought with gaps or difficult to interpret, or both. Attempts to reconstruct their evolution have focused on plastid phylogeny, but were limited by the amount and type of phylogenetic information contained within single genes. Among the 210 different protein-coding genes contained in the completely sequenced chloroplast genomes from a glaucocystophyte, a rhodophyte, a diatom, a euglenophyte and five land plants, we have now identified the set of 45 common to each and to a cyanobacterial outgroup genome. Phylogenetic inference with an alignment of 11,039 amino-acid positions per genome indicates that this information is sufficient--but just rarely so--to identify the rooted nine-taxon topology. We mapped the process of gene loss from chloroplast genomes across the inferred tree and found that, surprisingly, independent parallel gene losses in multiple lineages outnumber phylogenetically unique losses by more that 4:1. We identified homologues of 44 different plastid-encoded proteins as functional nuclear genes of chloroplast origin, providing evidence for endosymbiotic gene transfer to the nucleus in plants.

Cell Nucleus↗
PubMed2026

Radiomics as a spatial context for treatment decision-making in head and neck cancer.

Radiomics has been widely explored as a non-invasive biomarker in head and neck squamous cell carcinoma (HNSCC), yet its clinical role remains unclear. Tissue-based biomarkers differ in their susceptibility to spatial sampling. Biomarkers such as PD-L1 expression, immune-cell infiltration, necrosis, and immune exclusion may exhibit substantial spatial heterogeneity, whereas HPV/p16 status and some genomic alterations are generally more stable across the tumor. Nevertheless, localized sampling may incompletely capture heterogeneity in selected clinical contexts. This mismatch becomes clinically relevant when treatment decisions, particularly for chemoradiotherapy, immunotherapy, or de-escalation, are based on potentially non-representative biopsy findings. In this narrative review, we argue that the role of radiomics is not to outperform established biomarkers, but to contextualize them by capturing spatial heterogeneity related to hypoxia, necrosis, stromal architecture, and immune exclusion. We synthesize current evidence linking radiomic features to these biological processes and map them to specific clinical decision points, including larynx preservation, immunotherapy stratification, and recurrence assessment. Rather than serving as a standalone predictor, radiomics may provide complementary spatial information that helps identify situations in which biopsy-derived biomarkers should be interpreted with caution. Although current evidence is largely retrospective, radiomics offers a pragmatic framework for integrating spatial information into biomarker-guided clinical workflows.

Journal Article↗
PubMed2004

The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell cytotoxicity.

Hallmarks of the inflammatory process in Type I diabetes are macrophage activation, local release of beta-cell-toxic cytokines and infiltration of cytotoxic T lymphocytes. We have observed recently that mice overexpressing active FRK (fyn-related kinase)/RAK (previously named GTK/Bsk/IYK, where GTK stands for gut tyrosine kinase, Bsk for beta-cell Src-homology kinase and IYK for intestinal tyrosine kinase) in beta-cells exhibit increased susceptibility to beta-cell-toxic events, and therefore, we now attempt to find a more precise role for FRK/RAK in these processes. Phosphopeptide mapping of baculovirus-produced mouse FRK/RAK revealed an autophosphorylation pattern compatible with Tyr-394 being the main site. No evidence for in vitro phosphorylation of the C-terminal regulatory sites Tyr-497 and Tyr-504 was obtained, nor was there any indication of in vitro regulation of FRK/RAK kinase activity. Screening a panel of known tyrosine kinase inhibitors for their ability to inhibit FRK/RAK revealed several compounds that inhibited FRK/RAK, with a potency similar to that reported for their ability to inhibit other tyrosine kinases. Cytokine-induced islet toxicity was reduced in islets isolated from FRK/RAK knockout mice and this occurred without effects on the production of nitric oxide. Addition of the nitric oxide inhibitor nitroarginine to FRK/RAK knockout islets exposed to cytokines decreased cell death to a basal level. In normal islets, cytokine-induced cell death was inhibited by the addition of two FRK/RAK inhibitors, SU4984 and D-65495, or by transfection with short interfering RNA against FRK/RAK. It is concluded that FRK/RAK contributes to cytokine-induced beta-cell death, and inhibition of this kinase could provide means to suppress beta-cell destruction in Type I diabetes.

Animals↗
PubMed2001

GABA(A) and GABA(B) receptors on neocortical neurons are differentially distributed.

The distribution of functional neurotransmitter receptors on the surface of neurons is highly relevant for synaptic transmission and signal processing. To map functional GABA(A) and GABA(B) receptors on the somadendritic membrane of rat neocortical layer V pyramidal neurons we used patch-clamp recording in combination with infrared-guided laser stimulation to release gamma-aminobutyric acid (GABA) photolytically. The data strongly suggest that relatively more GABA(A) receptors are located at the apical dendrite and relatively more GABA(B) receptors near the soma. Such a specific distribution of GABA(A) and GABA(B) receptors may serve to compensate for differences in electrotonic voltage attenuation between GABA(A) and GABA(B) receptor-mediated inhibitory postsynaptic potentials (IPSPs).

Animals↗
PubMed2002

Cross-boundary working: implications for the multiprofessional team.

This paper explores cross-boundary working and the impact it may have on the manner in which multiprofessional teams function. It draws on data collected for a study commissioned by the Department of Health, Human Resource Initiative entitled Evaluating New Roles in Practice (ENRiP). A series of case studies formed one part of the study that aimed to map the process of implementation of new roles in practice, identify the organizational barriers and levers that affected the implementation process and explore the meaning of the new roles from the perspective of postholders, patients and stakeholders. A naturalistic approach to enquiry was taken using a combination of participant observation, interviews and reflection. The article includes an overview of the current context in which cross-boundary work is developing, a review of current literature related to multiprofessional issues and team-working, a brief descriptions of the typology of new roles that emerged as one strand of the ENRiP study, and the impact that these roles had on both interprofessional and multiprofessional working. It concludes with a discussion of the implications for practice and the need to ensure that both education and policy are considered in planning for the future.

Attitude of Health Personnel↗
PubMed1998

The genetic analysis of cancer.

During the past two decades an overwhelming amount of knowledge has been acquired on the molecular genetics of human cancer. It is now evident that cancer is essentially a genetic disease, arising from inherited and/or somatically acquired mutations at different genetic loci, and that tumourigenesis is a multistep process. Gene mapping studies of inherited cancer syndromes have resulted in the identification of many genes implicated in the initiation of tumours. Importantly, alterations of the same genes were also found to play a role in the development of common, non-familial tumours. The genes involved belong to distinct functional classes, and include proto-oncogenes and tumour suppressor genes, which are regulators of cellular growth and proliferation, cell adhesion and programmed cell death. Another class of cancer susceptibility genes consists of DNA repair genes, which are involved in maintaining genomic stability. In unravelling the genetic basis of cancer, the localization and identification of genes involved in tumourigenesis can be considered as the 'easy' part; determination of the normal physiological function of these genes and their precise role in tumourigenesis has proved to be much more difficult. In this review, we highlight some of the major breakthroughs in the field of cancer genetics, and discuss recent insights in the putative role of proto-oncogenes, tumour suppressor genes and DNA repair genes in the initiation and progression of cancer. Also, we point to some of the challenges to be faced in the coming years.

DNA, Neoplasm↗
PubMed2002

Diagnosis of AOS: definition and criteria.

Presented in this article is a discussion of current progress in behavioral, cognitive, and neuroanatomic definitions of apraxia of speech (AOS). A behavioral definition summarizes the speech symptoms that should be considered diagnostic of AOS with or without co-occurring aphasia and dysarthria. AOS is defined in cognitive terms as an impairment in the translation of phonological representations into specifications for articulation. Progress toward a neuroanatomic definition of AOS will rely on mapping the processes described by increasingly sophisticated cognitive models of normal speech production to the brain. The article describes criteria that have been proposed for differentiating apraxic from phonological and dysarthric disorders and suggests that syndrome-based approaches to the diagnosis of AOS may obscure important differences between individual presentations of apraxic disruption as well as similarities between AOS and other speech-language disorders.

Apraxias↗
PubMed2003

Dynamics of the interaction between a fibronectin molecule and a living bacterium under mechanical force.

Fibronectin (Fn) is an important mediator of bacterial invasions and of persistent infections like that of Staphylococcus epidermis. Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis takes place under physiological shear rates. We investigated the dynamics of the interaction between individual living S. epidermidis cells and single Fn molecules under mechanical force by using the scanning force microscope. The mechanical strength of this interaction and the binding site in the Fn molecule were determined. The energy landscape of the binding/unbinding process was mapped, and the force spectrum and the association and dissociation rate constants of the binding pair were measured. The interaction between S. epidermidis cells and Fn molecules is compared with those of two other protein/ligand pairs known to mediate different dynamic states of adhesion of cells under a hydrodynamic flow: the firm adhesion mediated by biotin/avidin interactions, and the rolling adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1 interactions. The inner barrier in the energy landscape of the Fn case characterizes a high-energy binding mode that can sustain larger deformations and for significantly longer times than the correspondent high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode. The association kinetics of the former interaction is much slower to settle than the latter. On this basis, the observations made at the macroscopic scale by other authors of a strong lability of the bacterial adhesions mediated by Fn under high turbulent flow are rationalized at the molecular level.

Avidin↗
PubMed2003

ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation.

Ataxia-telangiectasia Mutated (ATM), mutated in the human disorder ataxia-telangiectasia, is rapidly activated by DNA double strand breaks. The mechanism of activation remains unresolved, and it is uncertain whether autophosphorylation contributes to activation. We describe an in vitro immunoprecipitation system demonstrating activation of ATM kinase from unirradiated extracts by preincubation with ATP. Activation is both time- and ATP concentration-dependent, other nucleotides fail to activate ATM, and DNA is not required. ATP activation is specific for ATM since it is not observed with kinase-dead ATM, it requires Mn2+, and it is inhibited by wortmannin. Exposure of activated ATM to phosphatase abrogates activity, and repeat cycles of ATP and phosphatase treatment reveal a requirement for autophosphorylation in the activation process. Phosphopeptide mapping revealed similarities between the patterns of autophosphorylation for irradiated and ATP-treated ATM. Caffeine inhibited ATM kinase activity for substrates but did not interfere with ATM autophosphorylation. ATP failed to activate either A-T and rad3-related protein (ATR) or DNA-dependent protein kinase under these conditions, supporting the specificity for ATM. These data demonstrate that ATP can specifically induce activation of ATM by a mechanism involving autophosphorylation. The relationship of this activation to DNA damage activation remains unclear but represents a useful model for understanding in vivo activation.

Adenosine Triphosphate↗
PubMed2004

Advances in laboratory testing for HIV.

In 2004, the diagnosis of established human immunodeficiency virus (HIV) infection can be made with close to 100% assurity. The extraordinarily engineered performances of HIV-screening assays are unprecedented. The well-established confirmatory tests performed by well-versed laboratories using criteria that are well understood in order to interpret the results of these tests give highly accurate outcomes of diagnostic testing strategies. Furthermore, the ability to monitor the progress of the infection and the viral pathogenesis is possible through the use of tests that quantify viral load or the peripheral CD4+ T-cells and other lymphocyte sub-type levels. Newer laboratory testing mechanisms, such as assessment of reverse transcriptase activity and sophisticated cell staining and flow cytometric analyses, have been used to map disease processes and progress on a research level and may be used in future to fine-tune therapy and to follow disease progression in even greater detail. Regulation of all HIV tests is of the highest level in Australia. In-house tests will be expected to conform to the levels specified for commercially produced tests.

Clinical Laboratory Techniques↗
PubMed2003

The time course of negative repetition effects in post-cue naming.

It has previously been shown that when picture pairs are repeated across blocks in a post-cue naming task, former distractors are named faster than former targets: the "negative repetition effect" (Mayall, Humphreys, & Kotsanis, 2002). In the present study the time course of this effect was examined. Experiment 1 demonstrated that the effect became apparent after a lag of only two intervening trials, with former targets being named faster than former distractors after a lag of zero trials. Experiment 2 used a new baseline condition with repeated picture pairs for which no response was required on the first presentation. Comparisons with this baseline indicated that the negative repetition effect is the result of suppression of former targets as opposed to facilitation of former distractors. The results support the proposal of Mayall et al. that the negative repetition effect reflects a form of speech monitoring that is applied when there is competition in the process of mapping from semantics to name representations.

Adult↗