Does Physiological Blood Glucose Control Require an Adaptive Control Strategy?

To test the hypothesis that only an adaptive algorithm would guarantee optimal feedback control of glycemia in insulin-dependent diabetes, fasting chronically diabetic dogs at rest were subjected to short-term artificial beta cell treatment. Insulin was applied intravenously and an oral glucose load was given during the experiment. Employing the same dosing algorithm, three different control strategies were employed in a random order on different days: adaptive control (minimum variance controller, Test A), fixed command control using on-line parameter estimates (Test B), and fixed command control using off-line individually optimized dosage constants (Test C). Comparison was made to nondiabetic control animals. The glycemic profiles were entirely normal in Test A and C, but were distinctly elevated in Test B. The peripheral hyperinsulinaemia could, however, not be avoided by adaptive control. It is concluded that the restoration of physiological blood glucose control in insulin-dependent diabetes requires dosage parameters which are either continually adapted to the actual situation (adaptive control) or are optimized to meet the individual's needs. In the latter case, fixed command control may be employed. Peripheral hyperinsulinaemia cannot be avoided as long as insulin is administered by a posthepatic route.     

Modelling effects and their impact on the results of ATHLET solutions of Exercise 1 of the VVER-1000 Coolant Transient Benchmark

The VVER-1000 Coolant Transient Benchmark consists of two phases and refers to experimental data from the Kozloduy Unit 6 Nuclear Power Plant in Bulgaria. The paper describes the modelling features and their impact on the results of the Exercise 1, Phase 1 of the Benchmark obtained by two ATHLET user groups, namely GRS and NRI. The simulated transient is a main coolant pump (MCP) switching on in one loop at reduced power while three other MCPs are in operation. Particular attention is paid to the influence of the reactor vessel modelling and especially of the nodalization in the upper plenum. The comparison and discussion of the two simulation results confirm that the two solutions with the ATHLET system code achieve quite good system response of the plant transient.     

Carpal fractures in children

This study addresses the likelihood of false negative urine pregnancy test results, due to physiological urine dilution as described in some anecdotal reports. In this prospective study 320 pregnancy tests were performed on urine samples of varying concentrations obtained from 40 women, with suspected complications of early pregnancy, who had presented for ultrasound scans. Four different pregnancy tests were used and serum betahCG levels were measured quantitatively. Despite a mean fivefold increase in urine dilution, the pregnancy tests with low betahCG detection limits maintained maximal sensitivity. The detection of betahCG in dilute urine was adversely affected by using pregnancy tests with higher betahCG detection limits and these tests should be used with caution when assessing gynaecological emergencies.     

Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins

Physical forces play a fundamental role in the regulation of cell function in many tissues, but little is known about how cells are able to sense mechanical loads and realize signal transduction. Adhesion receptors like integrins are candidates for mechanotransducers. We used a magnetic drag force device to apply forces on integrin receptors in an osteoblastic cell line and studied the effect on tyrosine phosphorylation as a biochemical event in signal transduction. Mechanical stressing of both the beta1 and the alpha2 integrin subunit induced an enhanced tyrosine phosphorylation of proteins compared with integrin clustering. Application of cyclic forces with a frequency of 1 Hz was more effective than a continuous stress. Using Triton X-100 for cell extraction, we found that tyrosine-phosphorylated proteins became physically anchored to the cytoskeleton due to mechanical integrin loading. This cytoskeletal linkage was dependent on intracellular calcium. To see if mechanical integrin stressing induced further downstream signaling, we analyzed the activation of mitogen-activated protein (MAP) kinases and found an increased phosphorylation of MAP kinases due to mechanical stress. We conclude that integrins sense physical forces that control gene expression by activation of the MAP kinase pathway. The cytoskeleton may play a key role in the physical anchorage of activated signaling molecules, which enables the switch of physical forces to biochemical signaling events.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Action semantics-directed prototyping

We present a methodology for compiler synthesis based on Mosses-Watt's action semantics. Each action in action semantics notation is assigned specific “analysis functions”, such as a typing function and a binding-time function. When a language is given an action semantics, the typing and binding-time functions for the individual actions compose into typing and binding-time analyses for the language; these are implemented as the type checker and static semantics processor, respectively, in the synthesized compiler. Other analyses can be similarly formalized and implemented. We show a sample language semantics and its synthesized compiler, and we describe the compiler synthesizer that we have developed.     

Processing to optimize the strength of heavily drawn Cu-Nb alloys

Heavily drawn Cu-Nb alloys display quite high ultimate tensile strengths. A modification to the consumable arc-casting technique used to prepare these alloys is shown to decrease the as-cast niobium dendrite diameter,t ₀, and also increase strength. Evaluation of strength, niobium filament spacing and thickness data show that strength varies with as-cast niobium dendrite size as somewhere betweent _o ^–0.36 tot _o ^–0.50 . Splat-cooling techniques demonstrate that minimum niobium dendrite sizes as small as 0.22m are possible. These sizes are over a factor of 10 smaller than has been achieved by consumable arc casting, and it is therefore suggested that processing rapidly solidified powders of Cu-Nb alloys should have significant advantages for preparing high-strength heavily drawn Cu-Nb alloys.