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Excited states have been observed in the N=Z-2 odd-odd nucleus 48Mn for the first time. Through comparison with the structure of 48V, a first high-spin study of an odd-odd mirror pair has been achieved. Differences between the T=1 analogue states in this pair have been interpreted in terms of Coulomb effects, with the aid of shell-model calculations in the full pf valence space. Unlike other mirror pairs, the energy differences have been interpreted almost entirely as due to a monopole effect associated with smooth changes in radius (or deformation) as a function of angular momentum. In addition, the large energy shift between analogue negative-parity states is interpreted in terms of the electromagnetic spin-orbit interaction in nuclei.

One of the most important factors affecting the time taken to respond to a visual stimulus is contrast, and studies of reaction time can provide precise, quantitative information about the underlying signal processing. In this study we measured both saccadic and manual reaction times to step increments in target contrast. Our results over a range of initial contrasts are consistent with a simple model consisting of a noisy logarithmic transducer followed by a rise-to-threshold accumulator. A systematic comparison with previous contrast-processing models also shows that the commonly used method of linear regression may not be a particularly sensitive tool in deciding between them. We found similar parameters for the contrast processor in both saccadic and manual reaction times, as might be expected if a common target detection stage precedes each type of reaction.

This paper provides potential users of passive microseismic monitoring data with an outline of the decisions which need to be made prior to deciding whether or not to deploy a PMM system, defining the system’s specifications and issuing the statement of work to potential suppliers. It is also intended to summarize the issues and functional parameters which must be defined in order to ensure that the installed system will be useful for all stakeholders and that the actual installation process will be as stress free as possible.

Based upon current experience with large PMM systems being deployed in North America, North Africa and the Gulf the authors review the factors which should be considered when designing PMM systems for various types of reservoir monitoring applications. Using specific examples of PMM systems designed to monitor heavy oil production is North America, CO2 sequestration in North Africa, and production optimization in Saudi Arabia the key factors influencing the design and operational characteristics of cost effective PMM systems are reviewed. The paper concludes with a review of the features which will be incorporated in different types of PMM systems in the near future.

This paper discusses the acquisition, transfer and subsequent processing/presentation of data from four different permanent PMM installations. The installations differ in both size, location, data processing procedures and ultimate function. In terms of complexity, capability and addressability this new Aramco PMM system probably represents the current state of the art in permanents deployed, unmanned passive microseismic monitoring systems. The paper concludes with a review of system data handling capabilities as they currently, or will soon, exist using the characteristics of this new system for illustration purposes.

The authors discuss more than twenty years experience using passive microseismic monitoring techniques to monitor the behaviour of oil and gas reservoirs, underground openings (both mining and structural), and natural/artificial slopes. In the majority of these instances logistical and cost constraints have necessitated the dispersal of groups of sensors and their associated acquisition units. Under some circumstances this can give rise to complex problems when the data has to be recombined prior to processing. However, these problems are relatively minor when weighed against the cumulative benefits which accrue to the operations as a result of the utilization of high quality microseismic data acquired from an extensive sensor array operated for an extended period.

In recent years, we have carried out experiments at the University of Rochester’s Omega laser in which supersonic, dense-plasma jets are formed by the interaction of strong shocks in a complex target assembly (Foster et al., Phys. Plasmas 9 (2002) 2251). We describe recent, significant extensions to this work, in which we consider scaling of the experiment, the transition to turbulence, and astrophysical analogues. In new work at the Omega laser, we are developing an experiment in which a jet is formed by laser ablation of a titanium foil mounted over a titanium washer with a central, cylindrical hole. Some of the resulting shocked titanium expands, cools, and accelerates through the vacuum region (the hole in the washer) and then enters a cylinder of low-density foam as a jet. We discuss the design of this new experiment and present preliminary experimental data and results of simulations using AWE hydrocodes. In each case, the high Reynolds number of the jet suggests that turbulence should develop, although this behaviour cannot be reliably modelled by present, resolution-limited simulations (because of their low-numerical Reynolds number).

Detecting change in individual patients is an important goal of neuropsychological testing. However, limited information is available about test-retest changes, and well-validated prediction methods are lacking. Using a large nonclinical subject group (N = 384), we recently investigated test-retest reliabilities and practice effects on the Wechsler Adult Intelligence Scale and Halstead-Reitan Battery. Data from this group also were used to develop models for predicting follow-up test scores and establish confidence intervals around them. In this article we review those findings, examine their generalizability to new nonclinical and clinical groups, and explore the sensitivity of the prediction models to real change. Despite similarities across samples in reliability coefficients and practice effects, limits to the generalizability of prediction methods were found. Also, when multiple test measures were considered together, one or more "significant" changes were common in all (including stable) subject groups. By employing normative cut-offs that correct for this, sensitivity of the models to neurological recovery and deterioration was modest to good. More complex regression models were not more accurate than the simpler Reliable Change Index with correction for practice effects when confidence intervals for all methods were adjusted for variations in level of baseline test performance.

A novel glucose-responsive gel formulation was stabilised via covalent coupling to a carbomer resin. The gel formed between the plant lectin, concanavalin A and specific polysaccharides was stabilised to minimise leaching of gel components into the surroundings. This was required to prevent toxicity and to preserve the working mechanism of the formulation. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 974P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-responsive formulation that transformed from gel to sol in the presence of free glucose. The rheological properties and in vitro component and insulin release of the carbomer-stabilised gel were evaluated. A decrease in viscosity over a chosen glucose concentration range was exhibited by the carbomer-based gel. The testing of such a formulation in in vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels was restricted significantly with respect to a non-coupled gel. Insulin delivery in response to glucose in the physiologically relevant glucose concentration range was demonstrated using the carbomer-stabilised gel at 37 degrees C. The performance of this novel self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.

Categorization is a basic means of organizing the world around us and offers a simple way to process the mass of stimuli one perceives every day. The ability to categorize appears early in infancy, and has important ramifications for the acquisition of other cognitive capacities, but little is known of its development during childhood. We studied 48 children (7-15 years of age) and 14 adults using an animal/nonanimal visual categorization task while event-related potentials (ERPs) were recorded. Three components were measured: P1, N2, and P3. Behaviorally, the children performed the task very similarly to adults, although the children took longer to make categorization responses. Decreases in latencies (N2, P3) and amplitudes (P1, N2, P3) with age indicated that categorization processes continue to develop through childhood. P1 latency did not differ between the age groups. N2 latency, which is associated with stimulus categorization, reached adult levels at 9 years and P3 latency at 11 years of age. Age-related amplitude decreases started after the maturational changes in latencies were finished.

The acute effects of ultraprofound hypothermia and blood substitution (UHBS) on neuronal cell viability were examined in adult rat hippocampus, a brain region particularly vulnerable to ischemic cell death. UHBS was performed using either artificial cerebrospinal fluid (ACSF) or Hypothermosol, an "intracellular-type" hypothermic preservation solution. After the procedure, the hippocampus was sliced and tested for cellular viability using a combination of cellular fluorochromes that are markers for live cells (acridine orange) and dead cells (propidium iodide). UHBS with ACSF resulted in a variable degree of neuronal death within the hippocampal subfields CA1/CA3, and dentate granular layer and hilus (CA4). In contrast, UHBS with Hypothermosol consistently resulted in hippocampal slices with only mild neuronal death. Our results of preserved hippocampal neuronal viability with use of UHBS and Hypothermosol support the demonstrated central nervous system (CNS) protective effects of UHBS and Hypothermosol when used during prolonged cardiac arrest. The results of this study also suggest that UHBS and Hypothermosol may be useful in the preparation and maintenance of viable hippocampal tissue for physiological studies, especially those involving aged animals, which are particularly vulnerable to hypoxic-ischemic cellular injury

To demonstrate the three-dimensional vascular anatomy of monochorionic placental anastomoses in vivo, both arterioarterial and arteriovenous.Two-dimensional placental mapping techniques were used to locate arterioarterial and arteriovenous anastomoses. A freehand sweep was performed across the anastomotic site, and multiple images were stored to disk, at 17 Hz. These were then segmented to show only color information (vascular flow) using purpose-designed software (CQ analysis) and the files reconstructed into a three-dimensional volume, for multidirectional viewing and movie generation.Both arterioarterial and arteriovenous anastomoses could be visualized in detail. Reconstruction of a dual volume of gray-scale and segmented color images allowed recreation of the vascular anatomy within the placental substance, as well as retention of the original directional flow information.Detailed anastomotic anatomy can be demonstrated three dimensionally in vivo. Given the increasing evidence implicating various anastomotic configurations in pathological intertwin transfusion, this technique may prove useful in the antenatal assessment and treatment of monochorionic twin pregnancies.

This study explored the neurodiagnostic utility of 6 factor scores identified by recent exploratory and confirmatory factor analyses of the WAIS-III and WMS-III: Verbal Comprehension, Perceptual Organization, Processing Speed, Working Memory, Auditory Memory and Visual Memory. Factor scores were corrected for age. education, sex and ethnicity to minimize their influences on diagnostic accuracy. Cut-offs at 1, 1.5 and 2 standard deviations (SDs) below the standardization sample mean were applied to data from the overlapping test normative samples (N = 1073) and 6 clinical samples described in the WAIS-III/WMS-III Technical Manual (N = 126). The analyses suggest that a I SD cut-off yields the most balanced levels of sensitivity and specificity; more strict (1.5 or 2 SD) cut-offs generally result in trading modest gains in specificity for larger losses in sensitivity. Finally, using combinations of WAIS-III/WMS-III factors together as test batteries, we explored the sensitivity and specificity implications of varying diagnostic decision rules (e.g.,1 vs. 2 impaired factors = "impairment"). For most of the disorders considered here, even a small (e.g., 3 factor) WAIS-III/WMS-III battery provides quite good overall diagnostic accuracy.

Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two-fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function.

Sanderson and colleagues wonder whether people try to quit smoking when mood improves and whether this could explain the association between quitting and improved mood in some of our cohorts.1 2 However, in more than half the studies, participants’ mood was assessed initially and then all attempted to quit immediately, so improved mood cannot have caused the decision to quit. Could a third factor explain both the success of quit attempts and improvements in mood? This factor, selectively associated with quitting, would have to …

Cryopreservation of islets adds great flexibility to clinical islet transplant programs. Methods of islet cryopreservation have traditionally utilized permeating cryoprotectants contained within isotonic solutions without specifically addressing issues of ionic balances, buffering capacity, or oxygen free radicals that occur during hypothermic stresses. These factors may become significant issues during low-temperature storage and during the freezing and thawing process. Since its development in the early 1980s, the University of Wisconsin (UW) organ preservation solution has become the standard vascular flush and preservation solution. Recently, Hypothermosol preservation solution (HTS) was developed as a hypothermic blood substitute. The unique characteristics and composition of these preservation solutions may be important when developing solutions specific for the cryopreservation of cells and tissues. It was the aim of this study to evaluate these two hypothermic preservation solutions as the media used in cryopreservation of islets. Groups of canine islets [5000 islet equivalents (IE)/group] were cryopreserved using the standard protocol of stepwise addition of dimethyl sulfoxide (DMSO) to 2 M, controlled nucleation, slow cooling (0.25 degrees C/min), and rapid thawing (200 degrees C/min). The cryopreservation solutions were made with 1) UW solution, 2) HTS solution, or 3) Medium 199 solution with 10% fetal calf serum (FCS). Additional control groups included islets cryopreserved using 4) HTS, 5) UW solution, and 6) Medium 199 alone, without DMSO. Recovery of islets immediately following thawing was equivalent between the groups with the exception of the islets cryopreserved without DMSO (groups 4-6, p0.05). After 48 h of postcryopreservation tissue culture, islet recovery was highest in the groups frozen with UW and HTS (mean +/- SEM) (79.8 +/- 1.9% and 82.5 +/- 1.5%, p0.05 vs. group 3, 69.1 +/- 3.3%, p0.05, ANOVA). Less than 15% of the islets were recovered when they were cryopreserved without the cryoprotectant DMSO (groups 4-6). Functional viability was assessed by measuring the glucose-stimulated insulin secretion during static incubation after 48-h culture. The stimulation indexes were 4.6 +/- 1.0, 4.2 +/- 0.8, 3.6 +/- 1.2, 0.6 +/- 0.5, and 0.4 +/- 0.2 for islets in groups 1-5, respectively. This study demonstrates that postcryopreservation survival can be improved using intracellular-based preservation solutions, including UW or HTS, in conjunction with DMSO.

Lymphatic filarial nematodes are infected with endosymbiotic Wolbachia bacteria. Lipopolysaccharide from these bacteria is the major activator of innate inflammatory responses induced directly by the parasite. Here, we propose a mechanism by which Wolbachia initiates acute inflammatory responses associated with death of parasites, leading to acute filarial lymphangitis and adverse reactions to antifilarial chemotherapy. We also speculate that repeated exposure to acute inflammatory responses and the chronic release of bacteria, results in damage to infected lymphatics and desensitization of the innate immune system. These events will result in an increased susceptibility to opportunistic infections, which cause acute dermatolymphangitis associated with lymphoedema and elephantiasis. The recognition of the contribution of endosymbiotic bacteria to filarial disease could be exploited for clinical intervention by the targeting of bacteria with antibiotics in an attempt to reduce the development of filarial pathology.

Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well-characterized.To investigate the susceptibility of frontal lobe white matter to alcohol-associated metabolic change and to understand the nature of alcohol-related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years).Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, but this result was not found when both age and drinking history were used to predict the level of FWM NAA.Alcohol-associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol-induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause frontal lobe-specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.

The activity against filarial parasites of the antibiotics rifampicin, oxytetracycline and chloramphenicol was examined. In addition, transmission electron microscopy was used to study the effects of rifampicin and oxytetracycline on filarial tissues and on the endosymbiont bacterium, Wolbachia. When tested in vitro at a concentration of 50.0 microM, each of the three antibiotics significantly reduced the motility levels of male Onchocerca gutturosa. Rifampicin, however, was the most active, virtually immobilizing the parasite by the end of the 40-day trial and producing an 84% reduction in viability (as measured by formazan-based colorimetry). In tests against O. lienalis microfilariae (mff) in CBA mice, the numbers of mff recovered after treatment with oxytetracycline at 100, 25 or 6.5 mg/kg daily, for 15 days, were 56% (Por = 0.03), 38% (P0.05) and 45% (P = 0.05) less than that recovered from the untreated controls, respectively. In another trial in mice, rifampicin (100 mg/kg daily for 15 days) was found to be the most active (causing a 74% reduction in the number of mff recovered--approximately equal to that achieved with the positive control of a single dose of ivermectin at 2 microg/kg), with chloramphenicol also showing significant activity (39% reduction). In further, in-vivo trials, at three dose levels (100, 25 or 6.25 mg/kg daily, for 15 days), all three antibiotics were tested against adult Brugia pahangi in the peritoneal cavities of jirds. None of the antibiotics produced a significant reduction in the numbers of live worms recovered, although a marginal effect was observed in eight of the nine antibiotic-treated groups. A further extended trial with rifampicin and oxytetracycline resulted in 43% and 38% reductions in worm recoveries, respectively (not statistically significant but consistent with a marginal effect); some of these worms appeared less motile and qualitatively in poor condition compared with those recovered from untreated jirds. Ultrastructural studies of these treated worms revealed that virtually all of the endosymbiont bacteria had been cleared from the parasite tissues. The tissues of the adult worms appeared to be largely intact but with a granulomatous response of host cells adhering to some specimens. However, developing uterine forms appeared to be abnormal and extensively damaged, showing an abrogation of embryogenesis. In contrast, worms recovered from control animals contained large numbers of Wolbachia, had no adherent host cells, and showed normal ultrastructure; the female worms exhibited a full range of intra-uterine developing stages from eggs to stretched mff. It is likely that the activity of these antibiotics against the endosymbiont Wolbachia causes the observed antifilarial activity, although some direct effect of each drug on filarial viability cannot be ruled out.

To determine whether it is possible to identify in vivo placental arterio-venous anastomoses (AVAs) by color Doppler flow mapping.Three monochorionic twin pregnancies (one with and two without twin-to-twin transfusion syndrome) underwent placental mapping by color Doppler ultrasound. Placental vessels along the chorionic plate were recorded together with the direction of blood flow and their location in relation to the cord insertions and to superficial arterio-arterial anastomoses. Suggestive AVAs were mapped topographically and results were compared with the findings of formal postnatal placental injection studies.An AVA was identified in each of the three cases. Injection studies showed multiple AVAs. Each antenatally identified AVA was confirmed at placental injection study. Their placental location correlated to other landmarks as predicted by ultrasound.This preliminary report demonstrates that AVAs can be identified using color Doppler ultrasound. This may facilitate planning for highly selective ablation of AVAs, and shorter procedure times. Formal studies are now indicated to determine the accuracy of this technique.

To describe adaptive changes in torsional alignment that follow sustained cyclovergence in healthy humans.Eye movements were recorded binocularly from four healthy subjects using dual-coil scleral annuli. Cyclovergence movements were evoked over periods of 30 to 150 seconds using a stereoscopic display, presenting gratings of lines arranged horizontally, vertically, or at 45 degrees, subtending angles of up to 48 degrees. In- and excyclodisparities of 5 degrees were introduced and removed in a single-step fashion. After stimulation, the time course and magnitude of the decay in cyclovergence was compared with the subject either in darkness or viewing a baseline stimulus of zero cyclodisparity.As reported previously, the cyclovergence response to incyclodisparities was greater than to excyclodisparities. After sustained excyclovergence, however, in all subjects and in response to all orientations of the gratings, the decay in darkness was incomplete, implying an adaptive change in torsional alignment. In response to the horizontal gratings, for incyclovergence there was also an incomplete decay in darkness but to a lesser degree than in response to excyclovergence, and in only three of four subjects. The incyclovergence evoked by the oblique and vertical gratings was of small magnitude, and its decay was unaffected by the presence or absence of a visual stimulus.After sustained cyclovergence, its decay in the absence of a visual stimulus may be incomplete. The residual component may be interpreted, by analogy with horizontal and vertical vergence, as reflecting so-called phoria adaptation for torsional alignment.

This collection of reprints describes work performed under the three basic work elements of the contract during the period 10/01/96-09/30/97. The work elements are: (1) laboratory studies of key production and loss processes for IR-active species of special interest to upper atmospheric non-LTE IR emissions; (2) ground-based field measurements of selected IR airglow and auroral emissions, with emphasis on sources of background and clutter; (3) atmospheric modeling of the dynamics of the non-LTE processes relating to the laboratory and field measurements. Results from the laboratory studies include rate constants for the collisional relaxation of OH(X(sup 2)II, v, N) v = 1 (N = 8-25), v = 2 (N = 8-22), v = 3 (N = 9-17) by O2 and fractional populations of NO(v-1) resulting from collision-induced vibrational relaxation of NO(v = 3) by O atoms and NO (v = 2, 3) by NO. Results from the field measurements include a statistical study of the characteristics of > 50 wave events which were identified in airglow images obtained at equatorial latitudes, documentation of a technique for two-dimensional spectral analyses of mesospheric airglow image data, and the presentation of evidence for ducting and evanescence in selected wave events observed in the airglow over the Hawaiian islands. Results from the modeling effort include the use of ground-based image data for the OI 557.7-nm airglow emission for benchmarks to deduce the presence (and key properties) of wave activity near the base of the thermosphere, followed by use of the dynamical model to estimate the enhanced vertical diffusion resulting from the wave activity.

Individuals in short-term abstinence from chronic alcohol consumption commonly have neuropsychological impairments with parallel abnormalities in brain structure. Stable, long-term sobriety often results in improvements in both brain structure and function, although the mechanisms underlying these changes are currently not well understood.To investigate further the neurobiological underpinnings of alcohol-associated brain abnormalities in short-term and long-term abstinence from alcohol, proton magnetic resonance spectroscopy (echo time, 35 msec; repetition time, 1.5 sec) was used to assay metabolites in the anterior centrum semiovale, anterior cingulate gyrus, and right thalamus of two groups of non-Korsakoff alcoholic men, at different stages of abstinence, compared with a control group of alcohol-nonabusing men. Absolute concentrations of N-acetylaspartate, choline, myo-inositol, and creatine were measured in four recently detoxified alcoholics (mean age, 48.7 years; median abstinence, 41.5 days), five long-term abstinent alcoholics (mean age, 45.1 years; median abstinence, 1.7 years), and five nonalcoholic controls (mean age, 45.0 years).Although there were no between-group differences in concentrations of N-acetylaspartate, choline, or creatine, recently detoxified alcoholics had significantly higher myo-inositol in the thalamus, compared with controls and long-term abstinent alcoholics, and significantly higher myo-inositol in the anterior cingulate gyrus, compared with the controls.Elevations in myo-inositol in recently detoxified alcoholics are compatible with an acute alcohol cytotoxicity model. myo-Inositol is elevated in hyperosmolar states such as hypernatremia, renal failure, and diabetes; alcohol-induced hyperosmolarity may trigger accumulation of myo-inositol to stabilize the intracellular environment. Increases in myo-inositol may also reflect proliferation or activation of glia. The reduction of myo-inositol to control group levels in long-term abstinent alcoholics may reflect osmolar stability in abstinent alcoholics and/or a reduction in glial cell activation.

Cryopreserved valve homografts often fail in infants. Controversies are ongoing concerning the relative contributions of cryopreservation variables, immune responses, cellular viability, and durability of the extracellular matrix to the mode of tissue failure.Tissues to be examined for patterns of ice crystal distribution were cryopreserved. Tissue water was substituted with methanol and the tissues cryopreserved conventionally using dimethylsulfoxide, after which they were warmed and processed for light or electron microscopy. Selected specimens were vitrified to prevent ice crystal formation, cryopreserved, and subsequently warmed and processed for light and electron microscopy.Cryosubstitution of conventionally cryopreserved heart valves, while still frozen, demonstrated extensive extracellular ice formation, with smaller crystals in the ventricularis than in either the spongiosa or fibrosa. Extracellular ice formation was prevented by vitrification, a process in which the biological system is stabilized as an amorphous solid in the absence of crystalline ice.It is proposed that the extensive ice formation observed in conventionally cryopreserved heart valves may cause extracellular matrix damage that predisposes the valves to calcification. Future studies will assess the above hypothesis by comparison of conventional and ice-free (vitrification) cryopreservation methods in animal models of calcification.

Event-related potentials (ERPs) recorded from the human scalp can provide important information about how the human brain normally processes information and about how this processing may go awry in neurological or psychiatric disorders. Scientists using or studying ERPs must strive to overcome the many technical problems that can occur in the recording and analysis of these potentials. The methods and the results of these ERP studies must be published in a way that allows other scientists to understand exactly what was done so that they can, if necessary, replicate the experiments. The data must then be analyzed and presented in a way that allows different studies to be compared readily. This paper presents guidelines for recording ERPs and criteria for publishing the results.

Visual event-related potentials (ERPs) were examined in 16 children (aged 5-14 y) with phenylketonuria (PKU) and 16 age- and sex-matched controls. Lifetime median measures of phenylalanine (Phe) were 230-460 micromol/l. The most recent Phe levels were 56-624 micromol/l. ERPs were recorded whilst the children performed a discrimination task. All stimuli were square wave gratings degree, which appeared for 33 ms. A response to an infrequent grating that differed in orientation or spatial frequency was required. The older children with PKU had a delay in the first peak (P1) of the ERP, and age-related changes in the amplitude of P1. There was attenuation of the second peak across age groups in PKU. There was no evidence of reduced response accuracy or longer reaction times in children with PKU. Latencies of the cognitive P3 were not delayed in PKU. The delayed early peaks are consistent with previous studies that have shown delayed visual evoked potentials in PKU. The lack of differences in reaction time and P3 may be due to relatively good Phe control in children with PKU, or to the simplicity of the task. Suggestions are made for future ERP studies of PKU.

HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.

The three paradigms presented in this paper demonstrate the value of ERPs in examining the development of early cognitive processes. Although we have presented only three examples, early cognitive processing could be investigated in a wide range of paradigms using ERPs, in normal as well as clinical populations. Clearly, a next step in understanding the age-related changes in these cognitive processes is to employ dipole source localization to examine the involvement of different generators and their maturation. The final conclusion is that developmental studies are important as they can contribute to our understanding of models of processing and of the generators of ERPs, in terms of cognition as well as neuroanatomy. Hence, the models of cognitive processes in adults should include the development of those processes through childhood.

To clone, sequence, and express porcine recombinant soluble tumor necrosis factor receptor 1 (sTNFR1).A polymerase chain reaction (PCR)-based library enrichment technique was used to isolate a fragment of porcine TNFR1. The mature extracellular domain of porcine TNFR1 was subcloned into an expression vector and expressed in Escherichia coli as a fusion protein. Protein product was purified by immunoaffinity chromatography, using a commercially available affinity gel specific for the marker peptide of the fusion protein. The bioactivity of the purified protein was tested for its ability to inhibit TNF-mediated cytotoxicity in a PK(15) bioassay.A 927-base pair fragment of porcine TNFR1 encoding the entire extracellular and transmembrane domains, as well as 75 amino acids of the cytoplasmic domain, was isolated from a porcine lung cDNA library. The extracellular domain was expressed as a soluble TNFR1 fusion protein with a yield of 120 to 150 microg/L of culture. Affinity-purified porcine sTNFR1 was able to inhibit TNF-mediated cytotoxicity of porcine PK(15) cells in dose-dependent manner.Porcine recombinant sTNFR1 inhibits TNF bioactivity in vitro. This recombinant protein will be useful for developing TNFR1 antibodies and studying the roles of TNF and TNFR1 in the pathogenesis of infectious diseases in swine.

Th2 lymphocyte responses under the control of IL-4 and IL-5 are frequently associated with protective responses to parasitic helminths. Studies on the role of these cytokines in acquired resistance to parasitic nematodes indicate that, in the case of gastrointestinal nematodes, immunity is mediated by IL-4, while immunity to tissue-dwelling nematodes is dependent on IL-5. Here we investigate the role of IL-5 and eosinophils in protective immunity to Onchocerca microfilariae in IL-4-deficient mice. In the absence of IL-4, and despite the up-regulation of Th1-type responses, immunity remains dependent on IL-5 and eosinophils. Protection was unaffected by the absence of Ab in B cell-deficient mice, confirming that IL-5 is not acting via either B cell differentiation, Ag presentation, or isotype switching mechanisms. These data demonstrate the dissociation of IL-4 and IL-5 in a functional model of protective immunity to a tissue dwelling nematode and cast doubt on the role of IL-4 in the generation of CD4+ T cell-mediated, IL-5-dependent immunity to Onchocerca microfilariae. Importantly, they also segregate T cell-mediated mechanisms of protective immunity from those characterized in ocular pathologic responses in onchocerciasis, which are dependent on IL-4.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan,Price, 1986).

This study examines differential attention deficits in 19 temporal lobe epilepsy (TLE) patients, 15 generalized seizure patients (GSP), and 19 schizophrenic patients, compared to 20 normal controls. All participants were tested on a variable foreperiod reaction time (RT) task and continuous performance test (CPT). Temporal lobe epilepsy patients and schizophrenic patients show crossover deficits on the RT task requiring a conscious, effortful, preparatory motor set; while GSP show impairments on the CPT requiring vigilant, self-directed attention to external stimuli. The results suggest separate cortical and subcortical brain systems in the respective attentional deficits and in the etiologies of TLE, GSP, and schizophrenic disorders.

Quinuclidines with a 3-biaryl substituent are a new class of potent, orally active squalene synthase (SQS) inhibitors. Variants around these rigid structures indicate key structural requirements for cationic SQS inhibitors. Thus the lower in vitro potency found for quinuclidines bearing 3-substituents, which did not overlay the biphenyl group of 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (2) (IC50 = 16 nM, rat microsomal SQS), implied a directional requirement for the 3-substituent. Similarly, the lower potency of the 3-terphenyl analogue 6 (IC50 = 370 nM) indicated size constraints for this substituent. In compounds with a linking group between the quinuclidine and biphenyl ring, linking groups of lower lipophilicity were less well tolerated (e.g., 17, CH2CH2, IC50 = 5 nM vs 19, NHCO, IC50 = 1.2 microM). Replacement of the distal phenyl ring of 2 with a more polar pyridine heterocycle caused a reduction in in vitro potency. In general, good in vivo activity in the rat was restricted to 3-hydroxy analogues, with the 3-[4-(pyrid-4-yl)phenyl] derivative 39 (IC50 = 161 nM) showing the best inhibition (following oral dosing) of cholesterol biosynthesis from mevalonate (ED50 = 2.7 mg/kg).

Suspended animation is defined as the therapeutic induction of a state of tolerance to temporary complete systemic ischemia, i.w., protection-preservation of the whole organism during prolonged circulatory arrest (or = 1 hr), followed by resuscitation to survival without brain damage. The objectives of suspended animation include: a) helping to save victims of temporarily uncontrollable (internal) traumatic (e.g., combat casualties) or nontraumatic (e.g., ruptured aortic aneurysm) exsanguination, without severe brain trauma, by enabling evacuation and resuscitative surgery during circulatory arrest, followed by delayed resuscitation; b) helping to save some nontraumatic cases of sudden death, seemingly unresuscitable before definite repair; and c) enabling selected (elective) surgical procedures to be performed which are only feasible during a state of no blood flow. In the discussion session, investigators with suspended animation-relevant research interests brainstorm on present knowledge, future research potentials, and the advisability of a major research effort concerning this subject. The following topics are addressed: the epidemiologic facts of sudden death in combat casualties, which require a totally new resuscitative approach; the limits and potentials of reanimation research; complete reversibility of circulatory arrest of 1 hr in dogs under profound hypothermia (10 degrees C), induced and reversed by portable cardiopulmonary bypass; the need for a still elusive pharmacologic or chemical induction of suspended animation in the field; asanguinous profound hypothermic low-flow with cardiopulmonary bypass; electric anesthesia; opiate therapy; lessons learned by hypoxia tolerant vertebrate animals, hibernators, and freeze-tolerant animals (cryobiology); myocardial preservation during open-heart surgery; organ preservation for transplantation; and reperfusion-reoxygenation injury in vital organs, including the roles of nitric oxide and free radicals; and how cells (particularly cerebral neurons) die after transient prolonged ischemia and reperfusion. The majority of authors believe that seeking a breakthrough in suspended animation is not utopian, that ongoing communication between relevant research groups is indicated, and that a coordinated multicenter research effort, basic and applied, on suspended animation is justified.