Insulinomimetic effect on glucose transport by epidermal growth factor when combined with a major histocompatibility complex class I-derived peptide

Peptides derived from the alpha 1-region of the murine H-2Dk molecule enhance glucose uptake in rat adipose cells above the maximum obtained with insulin stimulation alone (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now describe that epidermal growth factor (EGF) in combination with the same peptides, Dk-(61-85) and Dk-(62-85), stimulates cellular glucose uptake 5-7 times over the basal level, i.e. to 30-50% of the maximal insulin effect. EGF alone increased glucose uptake by only approximately 50% above basal and the peptide alone by 100% above basal. Maximal effect of EGF and peptide was reached in 10-20 min with 30 microM peptide (EC50 10-15 microM) and 50 nM EGF (EC50 1-2 nM). The effect of EGF and peptide on glucose uptake was additive to that of insulin and peptide until the maximal level attained with insulin and peptide was reached. The combined effect of EGF plus peptide on glucose transport was associated with a recruitment of GLUT4 molecules to the plasma membrane. However, the phosphatidylinositol (PI) kinase which is activated by insulin was not activated by EGF plus peptide. Thus, the effect of EGF plus peptide on glucose uptake seems independent of the activity status of the insulin receptor. 125I-Labeled EGF bound specifically to rat adipose cells with an apparent affinity of approximately 2 nM and Bmax approximately 5 x 10(3). However, the major histocompatibility complex (MHC) peptides did not affect EGF-stimulated internalization of EGF receptor, in contrast to their effect on the insulin receptors. Transforming growth factor alpha had an effect similar to EGF on glucose uptake. Three other peptides derived from other parts of murine MHC class I had no effect on glucose uptake in combination with EGF. Thus, EGF in combination with certain MHC class I-derived peptides is insulinomimetic concerning glucose transport and this effect is independent of the insulin receptor activity.     

Academic faculty practices: issues for viability in competitive managed care markets

This study compares the perspectives of eighteen managed care executives and twenty-four faculty practice executives on critical policy issues related to the managed care marketplace. Market sites studied in 1994 included four major metropolitan areas: Minneapolis-St. Paul, Los Angeles, Philadelphia, and Atlanta. These markets were selected as being representative of communities with descending degrees of managed care involvement, but with significant market activity. Study participants from both managed care systems and faculty practices examined five policy issues: (1) the importance of including academic medical centers in current and future health care plans for marketing purposes; (2) the provision of clinical services that are unique to the academic medical center, that is, unavailable elsewhere in the community; (3) the degree of financial supplement that employers might pay for including an academic medical center; (4) future restructuring of organizations to sustain the educational mission of academic faculty within a viable delivery system; (5) satisfaction of managed care providers with graduates of academic medical centers, as measured by the clinical skills of graduate physicians. The study findings showed little support among managed care plans for paying supplements to include faculty practices in a health care network. Most study participants from managed care systems and academic faculty practices identified limited competencies that are unique to academic centers. Moreover, managed care organizations were only willing to undertake limited restructuring at best to include faculty practices within their networks. General concern about the preparation of resident physicians (especially those in primary care disciplines) for practice within contemporary managed care organizations existed among managed care informants. The results of the study indicate that as traditional funding sources for medical education are reduced, schools require greater integration with managed care plans to enable academic medical centers and their faculties to continue promoting clinical enterprise.     

The CD40-CD154 system in anti-infective host defense

Research in the past few years has documented significant advances in our understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions. This system influences many T cell mediated inflammatory immune responses and effector functions, unmasking a previously unexpected role for CD40-CD154 in cell mediated immunity. Manipulation of CD154 in animal models of infection by the use of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this system in the initiation of the inflammatory response, in the activation of antigen-presenting cells and in resistance to infections.     

Investigations of delamination criticality and the transferability of growth criteria

This article describes a study of delamination growth along 0 °/0 °, 0 °/ 5 °, ± 5 °, and 0 °/90 ° interfaces sandwiched between unidirectional carbon fibre/epoxy composite material. Relationships between damage criticality, growth rate and acoustic emission activity for delamination growth have been studied and the transferability of results from laboratory coupons to composite structural elements has been examined. Two types of coupon tests, conventional delamination beams and rigidly loaded single edge notched strips, have been compared for different mode ratios. Comparative tests have been made on buckling-induced delamination in plates. A graphite crack gauge has been used to measure delamination length and growth rate, ranging from 0.05–2000 m/s. Damage growth was also followed using visual, ultrasonic C-scan, X-ray radiography, macro-video and acoustic emission measurements. Empirical evaluations of interlaminar toughness for delamination beams are made using the Irwin-Kies relation. Unstable growth is analysed using elasto-dynamic moving finite elements. Bucklinginduced delamination is analysed using plate/shell FE methods with growth/remeshing algorithms.     

Tuning of MST neurons to spiral motions

Cells in the dorsal division of the medial superior temporal area (MSTd) have large receptive fields and respond to expansion/contraction, rotation, and translation motions. These same motions are generated as we move through the environment, leading investigators to suggest that area MSTd analyzes the optical flow. One influential idea suggests that navigation is achieved by decomposing the optical flow into the separate and discrete channels mentioned above, that is, expansion/contraction, rotation, and translation. We directly tested whether MSTd neurons perform such a decomposition by examining whether there are cells that are preferentially tuned to intermediate spiral motions, which combine both expansion/contraction and rotation components. The finding that many cells in MSTd are preferentially selective for spiral motions indicates that this simple three-channel decomposition hypothesis for MSTd does not appear to be correct. Instead, there is a continuum of patterns to which MSTd cells are selective. In addition, we find that MSTd cells maintain their selectivity when stimuli are moved to different locations in their large receptive fields. This position invariance indicates that MSTd cells selective for expansion cannot give precise information about the retinal location of the focus of expansion. Thus, individual MSTd neurons cannot code, in a precise fashion, the direction of heading by using the location of the focus of expansion. The only way this navigational information could be accurately derived from MSTd is through the use of a coarse, population encoding. Positional invariance and selectivity for a wide array of stimuli suggest that MSTd neurons encode patterns of motion per se, regardless of whether these motions are generated by moving objects or by motion induced by observer locomotion.     

Signal generation and transmission at 40, 80, and 160 Gb/s using a fiber-optical parametric pulse source

Short return-to-zero pulses (/spl sim/2 ps) are generated at bit rates of 40, 80, and 160 Gb/s using a fiber-optical parametric amplifier. The performance of the parametric pulse source is evaluated both back-to-back and in a 110-km transmission link. A receiver sensitivity of -33 dBm back-to-back was achieved after demultiplexing from 160 to 10 Gb/s. The power penalty at 160 Gb/s due to 110-km transmission was less than 2 dB. Very short pulses (0.5 ps) were also achieved when using the parametric amplifier as a compressor.