Computational and numerical methods for bioelectric field problems

Fundamental problems in electrophysiology can be studied by computationally modeling and simulating the associated microscopic and macroscopic bioelectric fields. To study such fields computationally, researchers have developed a variety of numerical and computational techniques. Advances in computer architectures have allowed researchers to model increasingly complex biophysical systems. Modeling such systems requires a researcher to apply a wide variety of computational and numerical methods to describe the underlying physics and physiology of the associated three-dimensional geometries. Issues naturally arise as to the accuracy and efficiency of such methods. In this paper we review computational and numerical methods of solving bioelectric field problems. The motivating applications represent a class of bioelectric field problems that arise in electrocardiography and electroencephalography.     

Magnetic susceptibility measurements of LHP and LNP crystals

Ferroelectric single crystals such as lead hydrogen phosphate (LHP) and dihydrated lead nitrate phosphate (LNP) have been derived from the diffusion of lead nitrate into the set gel containing orthophosphoric acid. By employing Faraday’s Gouy balance technique, the magnetic susceptibilities of LHP and LNP have been determined. It has been observed that (i) the gram and molar susceptibilities are independent of magnetic field, (ii)χ _M of LNP materials are greater than that of LHP materials and (iii) the positive values of magnetic susceptibilities suggest that LHP and LNP are paramagnetic materials.     

A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance

In the present study, we analyzed the cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of acute gout. The production of TNFalpha in synovial fluids reached the peak at 2 hours after the intra-articular injection of monosodium urate (MSU) crystals. The production of IL-1beta and IL-8 reached the first peak at 2 hours and the second peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached the peak at 9 hours. The source of TNFalpha and the first phase of IL-8 was synovial cells, whereas infiltrating leukocytes were the source of the second phase of IL-8 and also of IL-1beta and IL-1Ra. The production of TNFalpha was not altered by either anti-lL-8 IgG or IL-1Ra. The first IL-1beta peak was reduced only with a combination of anti-TNFalpha mAb and anti-lL-8 IgG, whereas the second peak was significantly reduced by either inhibitor. The first IL-8 peak was not altered with anti-TNFalpha mAb or IL-1 Ra, whereas the second IL-8 peak was reduced with IL-1Ra. Anti-TNFalpha mAb or anti-lL-8 IgG significantly reduced the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated the maximal leukocyte accumulation at 9 hours, but not the initial phase, which occurred within 2 hours. These results provide evidence that IL-8 and TNFalpha were responsible for the production of IL-1beta and IL-1Ra, and that IL-1beta was responsible for the second phase of IL-1beta and IL-8 production. Our data also suggest that the initial and the maximal phases of leukocyte influx are differently regulated. Finally, the intravenous injection of colchicine inhibited neutrophil infiltration without affecting the production of TNFalpha or the first peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis by directly inhibiting the migration of neutrophils.     

Immunoaffinity adsorption: Process-scale isolation of therapeutic-grade biochemicals

This review describes immunoaffinity purification as a tool for the processscale isolation of high-value, therapeutic-grade biochemicals from complex media. To this end, practicalities of activation, antigen coupling and operation in anti-human IgG monoclonal antibody recovery have been studied using cyanogen-bromide activated Sepharose CL-4B and composite Macrosorb K4AX immobilised with polyclonal human IgG as a model for general immunoaffinity systems. The characteristics required of solid phases are discussed in the context of the efficient application of bioselective processes early in the purification sequences. The importance of the technique for isolating biologically active biomolecules for in-vivo administration has been discussed in the light of current, stringent regulatory requirements. Finally, the prospect of scale-up and automation of the technique has been evaluated.     

Identification, purification, and characterization of a PA700-dependent activator of the proteasome

The activity of the intracellular protease, the proteasome, is modulated by a number of specific regulatory proteins. One such regulator, PA700, is a 700,000-Da multisubunit protein that activates hydrolytic activities of the proteasome via a mechanism that involves the ATP-dependent formation of a proteasome-PA700 complex. Four subunits of PA700 have been shown previously to be members of a protein family that contains a consensus sequence for ATP binding, and purified PA700 expresses ATPase activity. We report here the identification, purification, and initial characterization of a new modulator of the proteasome. The modulator has no direct effect on the activity of the proteasome, but enhances PA700 activation of the proteasome by up to 8-fold. This activation is associated with the formation of a proteasome/PA700-containing complex that is significantly larger than that formed in its absence. The modulator has a native Mr of approximately 300,000, as determined by gel filtration chromatography, and is composed of three electrophoretically distinct subunits with Mr values of 50,000, 42,000, and 27,000 (p50, p42, and p27, respectively). Amino acid sequence analysis of the subunits shows that p50 and p42 are members of the same ATP-binding protein family found in PA700. The p50 subunit is identical to TBP1, a protein previously reported to interact with human immunodeficiency virus Tat protein (Nelbock, P., Dillion, P. J., Perkins, A., and Rosen, C. A. (1990) Science 248, 1650-1653), while the p42 subunit seems to be a new member of the family. The p27 subunit has no significant sequence similarity to any previously described protein. Both p50 and p42, but not p27, were also identified as components of PA700, increasing the number of ATP-binding protein family members in this complex to six. Thus, p50 and p42 are subunits common to two protein complexes that regulate the proteasome. The PA700-dependent proteasome activator represents a new member of a growing list of proteins that regulate proteasome activity.     

Enhanced anticancer therapy mediated by specialized liposomes

OBJECTIVES: To determine whether instrument-proficient pilots would more safely manage a flight into unplanned instrument meteorologic conditions (IMC) than would nonproficient pilots. METHODS: A controlled experimental study was performed using a full-motion helicopter simulator. Participants were emergency medical services (EMS) pilots with commercial licenses and previous simulator experience who were blinded to the study design and hypothesis. During a simulated EMS mission, cloud ceiling and visibility were decreased until IMC prevailed, and pilot actions were recorded. Data included the altitude at which the aircraft entered IMC, and whether the pilots maintained control of the aircraft, flew within aviation standards (i.e., bank angle, airspeed), and safely landed. RESULTS: Twenty-eight pilots (13 instrument-proficient, 15 nonproficient) participated; they had a median of 6,300 hours of helicopter experience. Two pilots crashed, both from the nonproficient group. The instrument-proficient pilots lost control less often (15% vs 67%, p < 0.05), maintained instrument standards more often (77% vs 40%, p < 0.05), and entered IMC at a higher altitude (689 feet vs 517 feet, p < 0.05) compared with the nonproficient pilots. Instructor comments indicated that the nonproficient pilots made more errors than did the instrument-proficient pilots. CONCLUSIONS: Instrument-proficient pilots more safely manage an unexpected encounter with IMC. Helicopter EMS programs should strongly consider maintaining instrument proficiency to enhance safety.     

Spontaneous and induced minisatellite instability

Minisatellites provide not only the basis for DNA fingerprinting and DNA profiling but also extremely informative systems for analysing processes of tandem repeat turnover in the human genome. Minisatellite instability appears to involve distinct mutation processes in somatic and germline cells; in the germline, mutation is frequently dominated by inter-allelic conversion-like events most likely occurring at meiosis and apparently regulated by cis-acting mutation initiator elements. Attempts to define these initiators in transgenic mice have so far been thwarted by what appears to be a major human/mouse barrier to the inter-species transfer of repeat instability. Minisatellites not only show high frequency spontaneous mutation in the germline, but also appear to be very sensitive to mutation induction by ionizing radiation, both in experimentally irradiated mice and in human populations exposed following the Chernobyl disaster; the mechanisms of mutation induction by radiation remain enigmatic.     

Suitability and availability of sand deposits in Gujarat state of India with reference to their petrography

Gujarat is one of the western states of India. The workable sand deposits are available in shoals along number of rivers in the state. Since 1980 to 1982, 150 sand samples from 100 different rivers in the state have been collected and petrographically examined. The paper described the classification of the sand deposits into four different groups viz., (i) Kachchh Group (ii) Saurashtra Group (iii) North Gujarat Group (iv) South Gujarat Group. This classification is based upon the variation in percentage of various contituents and their physical as well as chemical properties. The authors have established the relationship of the sand deposits with provenance and the geomorphology of the area through which the rivers flow. They have recommanded the suitability of sand deposits of the above four groups based on physical and chemical properties of the constituents.     

Suicidal adolescents and ego defense mechanisms

OBJECTIVES: To identify defense mechanisms that characterize adolescents with a range of suicidal behaviors and to differentiate them from nonsuicidal adolescents. METHODS: Fifty-five suicidal adolescent inpatients admitted for a definite suicide attempt were compared with 87 adolescent inpatients who had no history of suicide attempt or ideation and 81 nonpatients. Defense mechanisms were assessed by the Ego Defense Scale (EDS) which is part of a larger semistructured interview, the Child Suicide Potential Scale (CSPS), and by a self-report questionnaire, the Life Style Index (LSI). The CSPS was also used to quantity violent and suicidal behaviors. RESULTS: On the LSI suicidal adolescent patients scored higher on denial, displacement, repression, and total defenses than the nonpatients. On the EDS they scored higher on regression, denial, projection, introjection, repression, and total defenses and lower on sublimation. LSI scores on displacement (higher) and on compensation (lower) distinguished suicidal from nonsuicidal inpatients. Denial and regression correlated positively and sublimation correlated negatively with both suicidal and violent behaviors. Introjection and repression correlated with suicidal behavior only. CONCLUSIONS: Overuse of displacement is connected with increased risk for suicidal and aggressive behaviors, while sublimation is probably a protective factor. In addition, several immature ego defenses possibly amplify aggression, which then is directed against the self by the maladaptive overuse of introjection, displacement, and repression.