Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation

Classic cadherins are adhesion-activated cell signaling receptors. In particular, homophilic cadherin ligation can directly activate Rho family GTPases and phosphatidylinositol 3-kinase (PI3-kinase), signaling molecules with the capacity to support the morphogenetic effects of these adhesion molecules during development and disease. However, the molecular basis for cadherin signaling has not been elucidated, nor is its precise contribution to cadherin function yet understood. One attractive hypothesis is that cadherin-activated signaling participates in stabilizing adhesive contacts ( Yap, A. S., and Kovacs, E. M. ( 2003) J. Cell Biol. 160, 11-16). We now report that minimal mutation of the cadherin cytoplasmic tail to uncouple binding of p120-ctn ablated the ability of E-cadherin to activate Rac. This was accompanied by profound defects in the capacity of cells to establish stable adhesive contacts, defects that were rescued by sustained Rac signaling. These data provide direct evidence for a role of cadherin-activated Rac signaling in contact formation and adhesive stabilization. In contrast, cadherin-activated PI3-kinase signaling was not affected by loss of p120-ctn binding. The molecular requirements for E-cadherin to activate Rac signaling thus appear distinct from those that stimulate PI3-kinase, and we postulate that p120-ctn may play a central role in the E-cadherin-Rac signaling pathway.

Two-Dimensional Failure Modeling with Minimal Repair

In this paper, we discuss two-dimensional failure modeling for a system where degradation is due to age and usage. We extend the concept of minimal repair for the one-dimensional case to the two-dimensional case and characterize the failures over a two-dimensional region under minimal repair. An application of this important result to a rnanufacturer's servicing costs for a two-dimensional warranty policy is given and we compare the minimal repair strategy with the strategy of replacement of failure. (C) 2003 Wiley Periodicals, Inc.

Increased adjuvant activity of minimal CD8 T cell peptides incorporated into lipid-core-peptides

A problem facing the use of subunit peptide and protein vaccines is their inability to stimulate protective immune responses. Many different approaches have been utilized to overcome this inefficient immune activation. The approach we have taken is to modify the vaccine antigen so that it now has adjuvant properties. To do this, multiple copies of minimal CD8 T cell epitopes were attached to a poly lysine lipid core. These constructs are known as lipid-core-peptides (LCP). The research presented here examines the adjuvant activity of LCP. Using mouse models, we were able to show that LCP were indeed able to activate antigen-presenting cells in vitro and to activate cytotoxic T-cell responses in vivo. More importantly, LCP were able to stimulate the development of a protective antitumour immune response.

Minimal instrumentation may compromise failure diagnosis with an ecological interface

Interfaces designed according to ecological interface design (EID) display higher-order relations and properties of a work domain so that adaptive operator problem solving can be better supported under unanticipated system conditions. Previous empirical studies of EID have assumed that the raw data required to derive and communicate higher-order information would be available and reliable. The present research examines the relative advantages of an EID interface over a conventional piping-and-instrumentation diagram (PID) when instrumentation is maximally or only minimally adequate. Results show an interaction between interface and the adequacy of the instrumentation. Failure diagnosis performance with the EID interface with maximally adequate instrumentation is best overall. Performance with the EID interface drops more drastically from maximally to minimally adequate instrumentation than does performance with the PID interface, to the point where the EID interface with minimally adequate instrumentation supports nonsignificantly worse performance than does the equivalent PID interface. Actual or potential applications of this research include design of instrumentation and displays for complex industrial processes.

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Background: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. Objective: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). Methods: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA, 211 with hip OA). Results: For knee and hip OA, MCII for absolute ( and relative) changes were, respectively, ( a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; ( b) -18.3 mm ( - 39.0%) and -15.2 mm ( -32.6%) for patient's global assessment; ( c) -9.1 ( -26.0%) and -7.9 ( -21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. Conclusion: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

On minimal models of process systems

Minimal representations are known to have no redundant elements, and are therefore of great importance. Based on the notions of performance and size indices and measures for process systems, the paper proposes conditions for a process model being minimal in a set of functionally equivalent models with respect to a size norm. Generalized versions of known procedures to obtain minimal process models for a given modelling goal, model reduction based on sensitivity analysis and incremental model building are proposed and discussed. The notions and procedures are illustrated and compared on a simple example, that of a simple nonlinear fermentation process with different modelling goals and on a case study of a heat exchanger modelling. (C) 2004 Elsevier Ltd. All rights reserved.

Minimal disease activity for rheumatoid arthritis: A preliminary definition

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: center dot The DAS28 definition places patients in MDA when DAS28

Optimal preventive maintenance of leased equipment with corrective minimal repairs

For leased equipment, the lessor carries out the maintenance of the equipment. Usually, the contract of lease specifies the penalty for equipment failures and for repairs not being carried out within specified time limits. This implies that optimal preventive maintenance policies must take these penalty costs into account and properly traded against the cost of preventive maintenance actions. The costs associated with failures are high as unplanned corrective maintenance actions are costly and the resulting penalties due to lease contract terms being violated. The paper develops a model to determine the optimal parameters of a preventive maintenance policy that takes into account all these costs to minimize the total expected cost to the lessor for new item lease. The parameters of the policy are (i) the number of preventive maintenance actions to be carried out over the lease period, (ii) the time instants for such actions, and (iii) the level of action. (c) 2005 Elsevier B.V. All rights reserved.

Erratum: Two-Dimensional Failure Modeling with Minimal Repair which appeared in this journal of April 2004, Volume 51:3 on pages 345–362

In this Erratum, we point out the reason for an error in the derivation of a result in our earlier paper, “Two-Dimensional Failure Modeling with Minimal Repair” [1], which appeared in the April 2004 issue of this journal, 51:3, on pages 345–362, and give the correct derivation.

A flaw in the use of minimal defining sets for secret sharing schemes

It is shown that in some cases it is possible to reconstruct a block design D uniquely from incomplete knowledge of a minimal defining set for D. This surprising result has implications for the use of minimal defining sets in secret sharing schemes.

Minimal Homogeneous Latin Trades

A latin trade is a subset of a latin square which may be replaced with a disjoint mate to obtain a new latin square. A d-homogeneous latin trade is one which intersects each row, each column and each entry of the latin square either 0 or d times. In this paper we give a construction for minimal d-homogeneous latin trades of size dm, for every integer d >= 3, and m >= 1.75d(2) + 3. We also improve this bound for small values of d. Our proof relies on the construction of cyclic sequences whose adjacent sums are distinct. (c) 2006 Elsevier B.V. All rights reserved.