Rules and exemplars in category learning

Psychological theories of categorization generally focus on either rule- or exemplar-based explanations. We present 2 experiments that show evidence of both rule induction and exemplar encoding as well as a connectionist model, ATRIUM, that specifies a mechanism for combining rule- and exemplar-based representation. In 2 experiments participants learned to classify items, most of which followed a simple rule, although there were a few frequently occurring exceptions. Experiment 1 examined how people extrapolate beyond the range of training. Experiment 2 examined the effect of instance frequency on generalization. Categorization behavior was well described by the model, in which exemplar representation is used for both rule and exception processing. A key element in correctly modeling these results was capturing the interaction between the rule- and exemplar-based representations by using shifts of attention between rules and exemplars.     

Lipiodol avidity of neuroendocrine liver metastases

AIMS: Lipiodol has been shown to concentrate in most hepatocellular carcinomas as well as in some liver metastases, including those of neuroendocrine origin. Our aim was to determine the proportion of neuroendocrine liver metastases that take up lipiodol and to identify tumour characteristics that predict avidity. METHODS: Avidity was assessed in 12 patients with neuroendocrine liver metastases by performing an abdominal CT scan immediately after selective hepatic arterial injection of 5 ml of unlabelled lipiodol and this was correlated with number and size of lesions as well as angiographic and plain CT scan features. RESULTS: In seven patients the tumours displayed lipiodol avidity (four solitary, three multiple); five patients had non-avid lesions (all multiple). A large dominant liver tumour was the only predictor of avidity (mean diameter of largest lesion 9 cm vs. 3 cm for patients with non-avid tumours: P=0.01). Avidity was not related to vascularity or CT density of lesions. CONCLUSIONS: Although this is a small study, it would appear that approximately 50% of neuroendocrine liver metastases selectively concentrate lipiodol, which could have implications for targeted cancer therapy.     

An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-alpha contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-alpha activity was inhibited through adenovirus-mediated gene transfer. We employed a replication-incompetent adenovirus-5 (Ad5) vector to endogenously express a TNF inhibitor (TNFi) gene, which encodes a chimeric protein consisting of the extracellular domain of the human 55-kDa TNF receptor joined to a mouse IgG heavy chain. Control animals consisted of rats infected with the same titer of adenovirus carrying the lac-z complementary DNA, encoding for beta-galactosidase. There was a significant reduction in plasma insulin and free fatty acid levels in TNFi obese rats 2 days following Ad5 administration. The peripheral insulin sensitivity index was 50% greater, whereas hepatic glucose output was completely suppressed during hyperinsulinemic glucose clamps in TNFi obese animals, with no differences observed between the two lean groups. The improvement in peripheral and hepatic sensitivity to insulin seen in the obese animals was independent of insulin receptor (IR) number and insulin binding affinity for IR. However, TNF-alpha neutralization led to a 2.5-fold increase in tyrosine phosphorylation of IR in skeletal muscle, whereas this was unchanged in liver. There was also a 4-fold increase in particulate protein tyrosine phosphatase activity of skeletal muscle in TNFi obese animals vs. beta-galactosidase controls, whereas protein tyrosine phosphatase activity in liver was unchanged. These results suggest that TNF-alpha is a mediator of insulin resistance in obesity and may modulate IR signaling in skeletal muscle and liver through different pathways. TNF-alpha may affect insulin action in the liver either at sites distal to the IR or indirectly, possibly because of increased provision of gluconeogenic substrates or altered counterregulation. In addition, the Ad5-mediated gene delivery system employed here provides an in vivo model that is efficient and economical for exploring mechanisms involved in TNF-alpha-induced insulin resistance in various genetic models of obesity-linked diabetes.     

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain

The characteristic features of a brain with Alzheimer disease (AD) include the presence of neuritic plaques composed of amyloid beta-protein (Abeta) and reductions in the levels of cholinergic markers. Neurotoxic responses to Abeta have been reported in vivo and in vitro, suggesting that the cholinergic deficit in AD brain may be secondary to the degeneration of cholinergic neurons caused by Abeta. However, it remains to be determined if Abeta contributes to the cholinergic deficit in AD brain by nontoxic effects. We examined the effects of synthetic Abeta peptides on the cholinergic properties of a mouse cell line, SN56, derived from basal forebrain cholinergic neurons. Abeta 1-42 and Abeta 1-28 reduced the acetylcholine (AcCho) content of the cells in a concentration-dependent fashion, whereas Abeta 1-16 was inactive. Maximal reductions of 43% and 33% were observed after a 48-h treatment with 100 nM of Abeta 1-42 and 50 pM of Abeta 1-28, respectively. Neither Abeta 1-28 nor Abeta 1-42 at a concentration of 100 nM and a treatment period of 2 weeks was toxic to the cells. Treatment of the cells with Abeta 25-28 (48 h; 100 nM) significantly decreased AcCho levels, suggesting that the sequence GSNK (aa 25-28) is responsible for the AcCho-reducing effect of Abeta. The reductions in AcCho levels caused by Abeta 1-42 and Abeta 1-28 were accompanied by proportional decreases in choline acetyltransferase activity. In contrast, acetylcholinesterase activity was unaltered, indicating that Abeta specifically reduces the synthesis of AcCho in SN56 cells. The reductions in AcCho content caused by Abeta 1-42 could be prevented by a cotreatment with all-trans-retinoic acid (10 nM), a compound previously shown to increase choline acetyltransferase mRNA expression in SN56 cells. These results demonstrate a nontoxic, suppressive effect of Abeta on AcCho synthesis, an action that may contribute to the cholinergic deficit in AD brain.     

Isolation and primary culture of rat Kupffer cells

The aim of this study was to describe a reproducible method for the isolation, purification and primary culture of rat Kupffer cells. Kupffer cells were isolated following sequential pronase/collagenase digestion of the liver and enrichment of a non-parenchymal cell fraction by a single-density gradient centrifugation step using 30% metrizamide. Kupffer cells were isolated and further purified from this cell fraction by centrifugal elutriation. Kupffer cells were isolated at 1017 g at 48-110 mL/min. All Kupffer cell fractions exhibited phagocytosis of 3 microm latex beads. Kupffer cell fractions isolated at 48 and 60 mL/min were predominantly ED2 negative while later fractions (80-110 mL/min) were ED2 positive. Kupffer cells were adherent in culture after 2 h. This method for Kupffer cell isolation resulted in a yield of 80-120 x 10(6) Kupffer cells per liver.     

The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress

Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild-type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: first, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments, we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesize that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments.     

Cadmium Telluride Solar Cells on Ultrathin Glass for Space Applications

This paper details the preliminary findings of a study to achieve a durable thin-film CdTe photovoltaic (PV) device structure on ultrathin space-qualified cover glass. An aluminum-doped zinc oxide (AZO) transparent conducting oxide was deposited directly onto the cover glass using metalorganic chemical vapor deposition (MOCVD). The AZO demonstrated low sheet resistance of 10 Ω/□ and high optical transparency of 85% as well as excellent adherence and environmental stability. Preliminary deposition of PV layers onto the AZO on cover glass, by MOCVD, showed the possibility of such a structure, yielding a device conversion efficiency of 7.2%. High series resistance (10 Ω cm²) and low V _oc (586 mV) were identified as the limiting factors when compared with the authors’ platform process on indium tin oxide-coated aluminosilicate. The coverage of the Cd_1?x Zn _x S window layer along with the front contacting of the device were shown to be the major causes of the low efficiency. Further deposition of AZO/CdTe employing an oxygen plasma cleaning step to the cover glass and evaporated gold front contacts significantly improved the device performance. With a highest conversion efficiency of 10.2%, series resistance improved to 4.4 Ω cm², open-circuit voltage (V _oc) up to 667 mV, and good adhesion, this represents the first demonstration of direct deposition of CdTe solar cells onto 100-μm-thick space-qualified cover glass.     

The effect of Medicare's payment system for rehabilitation hospitals on length of stay, charges, and total payments

BACKGROUND: Medicare's system for the payment of rehabilitation hospitals is based on limits derived from a hospital's average allowable charges per patient discharged during a base year. Thereafter, payments are capped but hospitals receive incentive payments if charges per patient are reduced in succeeding years. We hypothesized that per-patient charges would increase during the base year and then decrease in subsequent years. Hospitals would thus have higher reimbursement limits and receive incentive payments for reducing their charges. METHODS: We analyzed Medicare claims data for 190,921 discharges from 69 rehabilitation hospitals from 1987 through 1994. We compared total charges, length of stay, and interim payments before, during, and after each hospital's base year. RESULTS: After we controlled for inflation and temporal and seasonal trends, mean charges per patient discharged increased from $25,131 for patients discharged before the base year to $32,167 for patients discharged in the base year (a 28 percent increase, P<0.001) and the mean length of stay increased from 22.1 to 26.7 days (a 21 percent increase, P<0.001). After the base year, mean charges decreased to $29,307 (a 9 percent decrease) and the mean length of stay decreased to 24.0 days (a 10 percent decrease) (P<0.001 for both comparisons). Analysis of data on patients according to diagnosis -- for example, spinal cord injury, brain injury, stroke, amputations and deformities, hip fracture, and arthritis and joint disorders -- showed similar findings for each, with increases in charges and length of stay in the base year, followed by smaller reductions thereafter. For-profit hospitals had greater increases than nonprofit hospitals in their per-patient charges (mean increase, $7,434 vs. $2,929; P<0.001) and length of stay (mean increase, 4.6 vs. 2.3 days, P<0.001) during the base year. CONCLUSIONS: Although Medicare's reimbursement system for rehabilitation hospitals put an upper limit on total payments, its design was associated with substantial extra costs, including significantly increased payments to hospitals and doctors and increased numbers of hospital days for the average patient.     

A prospective, randomized study of the use of platelet concentrates irradiated with ultraviolet-B light in patients with hematologic malignancy

BACKGROUND: Irradiation of platelet concentrates (PCs) with ultraviolet-B (UVB) light inactivates the contaminating white cells and might be an alternative to filtration for the prevention of alloimmunization to HLA antigens and subsequent refractoriness to further platelet transfusions in multiply transfused patients with bone marrow failure. STUDY DESIGN AND METHODS: Patients with hematologic malignancy, mainly acute myeloid leukemia, were prospectively assigned in a random manner to receive either UVB-irradiated or control, nonirradiated PCs. All patients were given red cells that were white cell reduced by filtration. Transfusion efficacy and alloimmunization were assessed by means of corrected count increments, requirement for red cells and PCs, and measurement of lymphocyte-reactive antibodies. RESULTS: UVB-irradiated PCs had a clinical efficacy similar to controls as judged by corrected count increments at 1 to 6 and 12 to 24 hours and by the median requirement for red cell and platelet transfusions. Alloimmunization determined by measurements of lymphocyte-reactive antibodies using both conventional and antiglobulin-augmented lymphocytotoxicity techniques was not abolished in recipients of UVB-irradiated PCs (4/30, 13%) but was less than that in controls (5/20, 25%; p = NS). The mean number of platelet transfusion episodes prior to the occurrence of alloimmunization was greater in the control group (27 vs. 10; p = 0.017). CONCLUSION: In this trial, UVB irradiation did not diminish the clinical efficacy of platelet transfusions. There was a small but nonsignificant reduction alloimmunization, but no difference in refractoriness of the two groups was observed. Larger prospective randomized studies are required to confirm these findings and to compare UVB irradiation with white cell reduction.