Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor.

Signaling through growth factor receptors controls such diverse cell functions as proliferation, migration, and differentiation. A critical question has been how the activation of these receptors is regulated. Most, if not all, of the known ligands for these receptors are soluble factors. However, as matrix components are highly tissue-specific and change during development and pathology, it has been suggested that select growth factor receptors might be stimulated by binding to matrix components. Herein, we describe a new class of ligand for the epidermal growth factor (EGF) receptor (EGFR) found within the EGF-like repeats of tenascin-C, an antiadhesive matrix component present during organogenesis, development, and wound repair. Select EGF-like repeats of tenascin-C elicited mitogenesis and EGFR autophosphorylation in an EGFR-dependent manner. Micromolar concentrations of EGF-like repeats induced EGFR autophosphorylation and activated extracellular signal-regulated, mitogen-activated protein kinase to levels comparable to those induced by subsaturating levels of known EGFR ligands. EGFR-dependent adhesion was noted when the ligands were tethered to inert beads, simulating the physiologically relevant presentation of tenascin-C as hexabrachion, and suggesting an increase in avidity similar to that seen for integrin ligands upon surface binding. Specific binding to EGFR was further established by immunofluorescence detection of EGF-like repeats bound to cells and cross-linking of EGFR with the repeats. Both of these interactions were abolished upon competition by EGF and enhanced by dimerization of the EGF-like repeat. Such low affinity behavior would be expected for a matrix-tethered ligand; i.e., a ligand which acts from the matrix, presented continuously to cell surface EGF receptors, because it can neither diffuse away nor be internalized and degraded. These data identify a new class of insoluble growth factor ligands and a novel mode of activation for growth factor receptors

Exploring uplift modelling in direct marketing

Purpose: This research examines the importance of an uplift marketing model compared to traditional response models, used in direct marketing. Research Methodology: A multi-method research approach was used which included a survey using an electronic questionnaire and a semi-structured interview. Results: The research findings reveal that the value of employing uplift models in direct marketing. is that it factors change in behaviour from the action, which traditional response models do not. Limitation: The study was conducted in a single institution and focused only on scustomers with banking needs. Contribution: By employing an uplift model in direct marketing it is possible to increase marketing return-on-investment and positively impact brand loyalty and brand perception. Thus, marketers need to be cognizant of these findings and strategize accordingly. Keywords: Direct marketing, Customer management, Marketing model, Marketing communicatio

Instances and connectors : issues for a second generation process language

This work is supported by UK EPSRC grants GR/L34433 and GR/L32699Over the past decade a variety of process languages have been defined, used and evaluated. It is now possible to consider second generation languages based on this experience. Rather than develop a second generation wish list this position paper explores two issues: instances and connectors. Instances relate to the relationship between a process model as a description and the, possibly multiple, enacting instances which are created from it. Connectors refers to the issue of concurrency control and achieving a higher level of abstraction in how parts of a model interact. We believe that these issues are key to developing systems which can effectively support business processes, and that they have not received sufficient attention within the process modelling community. Through exploring these issues we also illustrate our approach to designing a second generation process language.Postprin

System Evolution, Feedback and Compliant Architectures

Proceedings, International Workshop on Feedback and Evolution in Software and Business Processes (FEAST 2000), Imperial College, London. Supported by EPSRCPostprintNon peer reviewe

Medicare Payment Policy: Does Cost Shifting Matter?

We examine cost shifting within the context of Medicare payment policy. We briefly review economic theory and available data and discuss the importance of cost shifting for policy. Then we present four central findings on cost shifting based on the views of former high-level policymakers. First, Medicare’s early (pre-prospective) payment policy was a boon to hospitals. Second, Medicare payment policy is a “top-down” affair, driven by budgetary and special-interest politics. Third, federal policymakers may not consciously consider cost shifting, but state policymakers do. Fourth, Medicare payment policy requires constant adjustment, but we are “getting it right” most of the time

Concorde noise-induced building vibrations John F. Kennedy International Airport

The outdoor and indoor noise levels resulting from aircraft flyovers and certain nonaircraft events were recorded at six home sites along with the associated vibration levels in the walls, windows, and floors of these test homes. Limited subjective tests conducted to examine the human detection and annoyance thresholds for building vibration and rattle caused by aircraft noise showed that both vibration and rattle were detected subjectively in several houses for some operations of both the Concorde and subsonic aircraft. Preliminary results indicate that the relationship between window vibration and aircraft noise is: (1) linear, with vibration levels being accurately predicted from OASPL levels measured near the window; (2) consistent from flyover to flyover for a given aircraft type under approach conditions; (3) no different for Concorde than for other conventional jet transports (in the case of window vibrations induced under approach power conditions); and (4) relatively high levels of window vibration measured during Concorde operations are due more to higher OASPL levels than to unique Concorde source characteristics

Predictors of fatigue severity in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort.

ObjectivesLongitudinal studies examining the baseline predictors of fatigue in SSc have not been reported. Our objectives were to examine the course of fatigue severity over time and to identify baseline clinical, demographic, and psychosocial predictors of sequentially obtained fatigue scores in early SSc. We also examined baseline predictors of change in fatigue severity over time.MethodsWe analyzed 1090 longitudinal Fatigue Severity Scale (FSS) scores belonging to 256 patients who were enrolled in the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS). Predictive significance of baseline variables for sequentially obtained FSS scores was examined with generalized linear mixed models. Predictors of change in FSS over time were examined by adding an interaction term between the baseline variable and time-in-study to the model.ResultsThe patients' mean age was 48.6 years, 47% were Caucasians, and 59% had diffuse cutaneous involvement. The mean disease duration at enrollment was 2.5 years. The FSS was obtained at enrollment and follow-up visits (mean follow-up time = 3.8 years). Average baseline FSS score was 4.7(±0.96). The FSS was relatively stable and did not show a consistent trend for change over time (p = 0.221). In a multivariable model of objective clinical variables, higher Medsger Gastrointestinal (p = 0.006) and Joint (p = 0.024) Severity Indices, and anti-U1-RNP antibodies (p = 0.024) were independent predictors of higher FSS. In the final model, ineffective coping skills captured by higher Illness Behavior Questionnaire scores (p<0.001), higher self-reported pain (p = 0.006), and higher Medsger Gastrointestinal Severity Index (p = 0.009) at enrollment were independent predictors of higher longitudinal FSS scores. Baseline DLco % predicted was the only independent variable that significantly predicted a change in FSS scores over time (p = 0.013), with lower DLco levels predicting an increase in FSS over time.ConclusionsThis study identified potentially modifiable clinical and psychological factors that predict longitudinal fatigue severity in early SSc

Facial recognition during early motherhood: Investigating the persistence of age and affect biases

Converging evidence demonstrates increased levels of sensitivity to infant faces in mothers. This may be reflective of a series of psychological and neurobiological changes that occur in the transition to, and during early, parenthood for the purpose of appropriate caregiving; however, this enhanced infant facial recognition is in contrast with the general adult literature regarding facial processing. In the current study, we aimed to replicate a prior study of emotion facial recognition in pregnant women in a sample of mothers with children under a year old, utilizing a paradigm in which adult and infant faces gradually changed from neutral expressions to either happy or sad expressions. Mothers were faster at the recognition of adult faces in comparison to infant faces, and were also faster at happy faces in comparison to sad faces. Results are discussed in context of the current processing literature regarding the perinatal period, and implications for the persistence of the own-age bias and happy face advantage are considered