Synthetic neural modeling applied to a real-world artifact.

We describe the general design, operating principles, and performance of a neurally organized, multiply adaptive device (NOMAD) under control of a nervous system simulated in a computer. The complete system, Darwin IV, is the latest in a series of models based on the theory of neuronal group selection, which postulates that adaptive behavior is the result of selection in somatic time among synaptic populations. The simulated brain of Darwin IV includes visual and motor areas that are connected with NOMAD by telemetry. Under suitable conditions, Darwin IV can be trained to track a light moving in a random path. After such training, it can approach colored blocks and collect them to a home position. Following a series of contacts with such blocks, value signals received through a "snout" that senses conductivity allow it to sort these blocks on the basis of differences in color associated with differences in their conductivity. Darwin IV represents a new approach to synthetic neural modeling (SNM), a technique in which large-scale computer simulations are employed to analyze the interactions among the nervous system, the phenotype, and the environment of a designed organism as behavior develops. Darwin IV retains the advantages of SNM while avoiding the difficulties and pitfalls of attempting to simulate a rich environment in addition to a brain.     

Hepatitis B and C in doctors and dentists in Nigeria

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.      

Theories and measures of consciousness: an extended framework

A recent theoretical emphasis on complex interactions within neural systems underlying consciousness has been accompanied by proposals for the quantitative characterization of these interactions. In this article, we distinguish key aspects of consciousness that are amenable to quantitative measurement from those that are not. We carry out a formal analysis of the strengths and limitations of three quantitative measures of dynamical complexity in the neural systems underlying consciousness: neural complexity, information integration, and causal density. We find that no single measure fully captures the multidimensional complexity of these systems, and all of these measures have practical limitations. Our analysis suggests guidelines for the specification of alternative measures which, in combination, may improve the quantitative characterization of conscious neural systems. Given that some aspects of consciousness are likely to resist quantification altogether, we conclude that a satisfactory theory is likely to be one that combines both qualitative and quantitative elements.     

Hepatitis B virus DNA in the serum of Sardinian blood donors negative for the hepatitis B surface antigen

The high endemicity of hepatitis B virus (HBV) infection and liver disease in Sardinia led us to assess the occurrence of HBV DNA in 1,411 sera of two selected groups of hepatitis B surface antigen (HBsAg)- negative blood donors: 793 with abnormal serum alanine aminotransferase (ALT) and 618 with normal serum ALT values (determined during routine testing of their blood donation). HBV DNA sequences were detected by dot-blot hybridization in 68 of 793 subjects (9%) with abnormal ALT but only in three of 618 subjects (0.5%) with normal ALT. HBV-core antibody (anti-HBc) was detected in 338 of 793 subjects (43%) with abnormal ALT as well as in 125 of 618 subjects (20.2%) with normal ALT. Among the 71 subjects positive for serum HBV DNA, 22 (31%) were positive for anti- HBc, while 49 (69%) were negative for all serologic markers of HBV infection. Thus, a high frequency of anti-HBc in apparently healthy HBsAg-negative individuals and a high prevalence of serum HBV DNA in the absence of immunologic markers of HBV infection suggest the existence of genetic variants of HBV that may be responsible for some of the presumed NANB hepatitis encountered in Sardinia and possibly other areas of high endemicity for HBV.     

Early detection of antibodies against rDNA-produced HIV proteins with a flow cytometric assay

There is evidence that some human immunodeficiency virus (HIV)-infected individuals have prolonged periods of seronegativity. A flow cytometric immunoreactive bead (IRB) assay is described for quantitative, simultaneous, and early detection of antibodies to HIV. Polystyrene beads of four diameters, each size coated with a different HIV recombinant DNA-produced protein (p24, p31, gp41, or gp120), bound anti- HIV antibodies detected with fluorescent antiglobulin. The IRB assay was performed on a panel of blood donor samples, many giving consistently false-positive enzyme immunoassay (EIA) and indeterminant Western blot (WB) results. The IRB assay proved as sensitive and more specific than currently licensed EIA and WB tests. Results on serial samples from eight HIV-infected individuals indicated that quantitation of anti-p24 by IRB assay may be useful in monitoring disease progression. Sequential pre- and post-EIA seroconversion sera from 35 HIV-infected homosexual men were tested by the IRB assay using IgM- and IgG-specific fluorescent probes. All 35 cases were IRB assay positive for at least one rDNA-p either before (17 of 35, 49%) or at the time of EIA positivity. Eleven cases (31%) initially had only IgM anti-HIV, primarily to gp41 (17%). In two individuals, the IgM response was detected at least 18 months before EIA seroconversion. The IRB assay is a widely applicable analytic procedure, potentially useful in pretransfusion anti-HIV screening of blood.     

Selective networks capable of representative transformations, limited generalizations, and associative memory.

Two parallel sets of selective networks composed of intercommunicating neuron-like elements have been connected to produce a new kind of automaton capable of limited recognition of two-dimensional patterns. Salient features of this automaton are (i) preestablished unchanging connectivity, (ii) preassigned connection strengths that are selectively altered according to experience, (iii) local feature detection in one network with simultaneous global feature correlation in the other, and (iv) reentrant interactions between the two networks to generate a new function, associative memory. No forced learning, explicit semantic rules, or a priori instructions are used.     

Relationship between tumor necrosis factor-α and liver fibrosis

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Chloride transport in primary cultures of rabbit colonocytes at different stages of development

BACKGROUND & AIMS: Ontogeny of colonic Cl- transport and its regulation has been characterized inadequately. The aim of this report was to study developmental changes in Cl- transport in primary cultures of rabbit distal colonocytes. METHODS: Colonocytes from newborn (7-9 days old), weanling (25-28 days old), and adult (6 months old) rabbits were cultured for 24 hours on a collagen IV matrix, and Cl- transport was measured using the fluoroprobe 6-methoxyquinolyl acetoethyl ester. RESULTS: Cl- permeabilities were dependent on [Cl-]o with maximal rates (in millimoles per liter per second) at [Cl-]o = 75 mmol/L (newborns; 0.15 +/- 0.04; weanlings; 0.2 +/- 0.02; and adults, 0.32 +/- 0.06). Influx was inhibited significantly by the Cl- channel (50 mumol/L diphenylamine-2-carboxylate) and the Na(+)-K(+)- 2Cl- cotransport (10 mumol/L furosemide) inhibitors. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretagogues, prostaglandin E1 (1 mumol/L), forskolin (1 mumol/L), and 8-bromo-cAMP (100 mumol/L), and the protein kinase C activator, phorbol 12-13 dibutyrate (1 mumol/L), increased Cl- influx significantly in all groups with adults showing greatest stimulation. However, taurodeoxycholate (0.025-1 mmol/L) had an effect only in the adult and the guanosine 3',5'-cyclic monophosphate (cGMP) activators STa and 8-bromo-cGMP had no effect. CONCLUSIONS: Rabbit distal colonocytes possess inhibitor-sensitive Cl- permeabilities even in neonates. However, the ontogeny of their regulation depends on the secretagogue-signaling pathway. (Gastroenterology 1996 Dec;111(6):1541-50)     

Electroporation of synthetic oligodeoxynucleotides: a novel technique for ex vivo bone marrow purging

Recent data suggest that tumor cells contaminating reinfused bone marrow may contribute to relapse in patients undergoing autologous bone marrow transplantation. Purging strategies that are able to remove these contaminating tumor cells need to be developed. This study describes how electroporation (EP) can be used to improve intracellular delivery of synthetic antisense oligodeoxynucleotides (ODNs), thereby enhancing their ability to suppress a target protein. Antisense ODNs that were introduced into cells by EP led to immediate suppression of targeted c-myc protein; this was associated with rapid cell death in the diffuse histiocytic lymphoma, U937; Burkitt's lymphoma, ST486; breast carcinoma, MCF-7; and Ewing's sarcoma, CHP-100, cell lines. Electroporation was found to have little or no detrimental effect on cells responsible for murine hematopoietic long-term reconstitution as determined from in vivo competitive repopulation studies. Using human c- myc-directed antisense ODNs as a model for the application of this approach to bone marrow purging, selective killing of human lymphoma U937 cells relative to normal human bone marrow cells was shown in cell mixing studies. In vivo studies were performed in which a survival advantage was shown for athymic mice that were inoculated with antisense-treated U937 cells as opposed to control cells. These studies suggest that EP of bone marrow may be of use in enhancing intracellular delivery of a variety of molecular/pharmaceutical agents. Taken together, these data suggest that the use of electroporation to enhance delivery of antisense ODNs is a promising new approach towards ex vivo bone marrow purging.