Characterization of antibodies to the insulin receptor: a cause of insulin-resistant diabetes in man

We have characterized the circulating inhibitor of insulin receptor binding found in several patients with a new syndrome of extreme insulin resistance. The inhibitor is an immunoglobulin by multiple criteria, including precipitation by 33% ammonium sulfate, migration on G-200 Sephadex gel filtration and DEAE chromatography, and immuno-precipitation with specific anti-human immuno-globulins. Although predominantly IgG, some activity is found in the IgM fraction of the immunoglobulins in one patient. The inhibitory immunoglobulins reacted with antisera to both kappa and lambda light chain determinants and are therefore polyclonal. In addition, activity is retained in the F(ab')2 fraction of pepsin-digested IgG. Evidence suggests that these antibodies are directed at determinants on or near the insulin receptor, and that they are responsible for the observed clinical insulin resistance.     

Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action

Autoantibodies to the insulin receptor have been detected in the sera of several patients with the Type B syndrome of insulin resistance and acanthosis nigricans. In this study we have used three of these sera (B-1, B-2, and B-3) as probes of the insulin receptor in isolated rat adipocytes. Preincubation of adipocytes with each of the three sera resulted in an inhibition of subsequent [(125)I]insulin binding. 50% inhibition of binding occurred with serum dilutions of 1:5 to 1:7,500. As in our previous studies with other tissues, Scatchard analysis of the insulin-binding data was curvilinear consistent with negative cooperativity. Computer analysis suggested that in each case the inhibition of binding was due to a decrease in receptor affinity rather than a change in available receptor number. In addition to the effects on insulin binding, adipocytes pretreated with antireceptor sera also showed alterations in biological responses. All three sera produced some stimulation of basal glucose oxidation. With serum B-3, maximal stimulation of glucose oxidation occurred at a serum concentration that inhibited binding by only 10-15%, whereas with serum B-2 the dilution curves for inhibition of binding and stimulation of glucose oxidation were superimposable. Serum B-1 behaved as a partial agonist; that is, it inhibited binding more effectively than it stimulated glucose oxidation. Cells pretreated with this serum in a concentration which inhibited binding by 80% also showed a five-fold shift to the right in the dose response of insulin-stimulated glucose oxidation, whereas spermine-stimulated glucose oxidation was unaffected. Serum B-2, which contained the highest titer of antireceptor antibodies, also stimulated 2-deoxy-glucose transport, as well as glucose incorporation into lipid and glycogen. Both the ability of the serum to inhibit binding and stimulate glucose utilization were enriched in purified immunoglobulin fractions and retained in the F(ab')(2) fragment of the IgG. In addition, the bioactivity was blocked by antihuman IgG but not by anti-insulin antibodies. Enzymatic digestion of adipocytes with trypsin resulted in a complete loss of insulin-stimulated bioactivity of serum B-3, but had only minor effects on the glucose oxidation produced by serum B-1 or B-2.These data suggest that the antibodies present in these three sera bind to different determinants on the insulin receptor. Thus, these antibodies may be useful probes of receptor structure and function.     

Defining global leadership in business environments.

Reviews evolutionary models of corporate globalization, distinguishing between international and global firms. To define global leadership, a distinction is made between the content of the activities of leaders in corporations within industries, and the style in which they conduct their affairs. The role of perception in cross-cultural interaction and leadership style is demonstrated by reviewing cross-national research. Alternatives to corporate global leadership are also suggested. Two models of global leadership training designed by multinational corporations are presented. Recommendations for preparing corporate leadership for global business are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Wood-chip fuel slashes hospital's steam costs.

Two 25,000 lb per hr steam boilers serve hospital's HVAC and process loads by using waste from logging to provide an economical biomass alternative to conventional fuels.     

Prevalence of specific anti-Cryptosporidium IgG, IgM and IgA antibodies in cat sera using an indirect immunofluorescence antibody test

Sera from 258 healthy and sick domestic and feral cats were screened for specific anti-Cryptosporidium antibodies using an indirect immunofluorescence antibody test (IFA). Sera were positive for IgG, IgM and IgA antibodies in 192 (74%), 84 (32%) and 67 (26%) samples, respectively. Antibody was not detected at dilutions of 1:10 and 1:20 or greater in any of eight specific pathogen-free kittens. IgM and IgA antibody classes were more prevalent in sick than in healthy domestic cats. The presence of IgM and/or IgA antibodies indicated early infection. However, these antibody classes were present in sera from cats either positive or negative for Cryptosporidium infection by faecal examination. Pronounced polar fluorescence was observed in the sporozoites in positive samples under fluorescence microscopy. The higher prevalence of specific anti-Cryptosporidium antibodies and the absence of Cryptosporidium oocysts in faecal samples from some IFA-positive animals suggests that detection of these antibodies in sera from cats could be helpful for the diagnosis of feline cryptosporidiosis.     

Imprinting of Local Metallic States into VO2 with Ultraviolet Light

Materials exhibiting electronic phase transitions have attracted widespread attention. By switching between metallic and insulating states under external stimuli, the accompanying changes in the electrical and optical properties can be harnessed in novel electronic and optical applications. In this work, a laterally confined conductive pattern is inscribed into an otherwise insulating VO₂ thin film using ultraviolet light, inducing an almost four orders of magnitude decrease in electrical resistivity of the exposed area. The metallic imprint remains in VO₂ after ultraviolet light exposure and can be completely erased by a short low temperature anneal. The ability to optically pattern confined metallic structures provides new opportunities for reconfigurable photonic and plasmonic structures, as well as re‐writable electric circuitry.     

Corrosion of ISG fibers in alkaline solutions

The corrosion behavior of glass fibers synthesized from the International Simple Glass (ISG) reference ingot, an international High‐Level Waste (HLW) borosilicate glass standard, is reported. Bundles of glass fibers were submerged in 120 mL of four different solutions of initial pH values (pH_i) of 9.5, 10.5, 11.5, and 12.5 for static corrosion testing. While all the experiments reached a residual corrosion rate after ~50 days, which remained approximately constant for the duration of the pH_i 9.5‐11.5 experiments, the pH_i 12.5 experiment underwent a Stage II→III dissolution transition after 57 days. This transition was preceded by a decrease in the Al concentration in solution followed by an increase in B and Si concentration in the leachate. Zeolite NaP2 was observed to form on these fibers via scanning electron microscopy and X‐ray diffraction—the crystallinity of the fibers was estimated to be ~40%‐45% (relative to amorphous component) after the Stage II→III transition. Transmission electron microscopy cross‐sectional imaging of sampled fibers revealed several porous layers on the pH_i 9.5‐11.5 samples, and a more aggressive alteration mechanism in the pH_i 12.5 fibers. Potential markers that indicate a transition from Stage II→Stage III corrosion are shown to occur based on experimental observations.     

Learning-enhanced simulated annealing: method,evaluation, and application to lung nodule registration

Simulated Annealing (SA) is a popular global minimization method. Two weaknesses are associated with standard SA: firstly, the search process is memory-less and therefore can not avoid revisiting regions that are less likely to contain global minimum; and secondly the randomness in generating a new trial does not utilize the information gained during the search and therefore, the search can not be guided to more promising regions. In this paper, we present the Learning-Enhanced Simulated Annealing (LESA) method to overcome these two difficulties. It adds a Knowledge Base (KB) trial generator, which is combined with the usual SA trial generator to form the new trial for a given temperature. LESA does not require any domain knowledge and, instead, initializes its knowledge base during a “burn-in” phase using random samples of the search space, and, following that, updates the knowledge base at each iteration. This method was applied to 9 standard test functions and a clinical application of lung nodule registration, resulting in superior performance compared to SA. For the 9 test functions, the performance of LESA was significantly better than SA in 8 functions and comparable in 1 function. For the lung nodule registration application, the residual error of LESA was significantly smaller than that produced by a recently published SA system, and the convergence time was significantly faster (9.3±3.2 times). We also give a proof of LESA’s ergodicity, and discuss the conditions under which LESA has a higher probability of converging to the true global minimum compared to SA at infinite annealing time.     

Polyp enhancing level set evolution of colon wall: method and pilot study

Computer aided detection (CAD) in computed tomography colonography (CTC) aims at detecting colonic polyps that are the precursors of colon cancer. In this work, we propose a colon wall evolution algorithm polyp enhancing level sets (PELS) based on the level-set formulation that regularizes and enhances polyps as a preprocessing step to CTC CAD algorithms. The underlying idea is to evolve the polyps towards spherical protrusions on the colon wall while keeping other structures, such as haustral folds, relatively unchanged and, thereby, potentially improve the performance of CTC CAD algorithms, especially for smaller polyps. To evaluate our methods, we conducted a pilot study using an arbitrarily chosen CTC CAD method, the surface normal overlap (SNO) CAD algorithm, on a nine patient CTC data set with 47 polyps of sizes ranging from 2.0 to 17.0 mm in diameter. PELS increased the maximum sensitivity by 8.1% (from 21/37 to 24/37) for small polyps of sizes ranging from 5.0 to 9.0 mm in diameter. This is accompanied by a statistically significant separation between small polyps and false positives. PELS did not change the CTC CAD performance significantly for larger polyps.