Temporal and spatial mapping of red grouper Epinephelus morio sound production.

The goals of this project were to determine the daily, seasonal and spatial patterns of red grouper Epinephelus morio sound production on the West Florida Shelf (WFS) using passive acoustics. An 11 month time series of acoustic data from fixed recorders deployed at a known E. morio aggregation site showed that E. morio produce sounds throughout the day and during all months of the year. Increased calling (number of files containing E. morio sound) was correlated to sunrise and sunset, and peaked in late summer (July and August) and early winter (November and December). Due to the ubiquitous production of sound, large-scale spatial mapping across the WFS of E. morio sound production was feasible using recordings from shorter duration-fixed location recorders and autonomous underwater vehicles (AUVs). Epinephelus morio were primarily recorded in waters 15-93 m deep, with increased sound production detected in hard bottom areas and within the Steamboat Lumps Marine Protected Area (Steamboat Lumps). AUV tracks through Steamboat Lumps, an offshore marine reserve where E. morio hole excavations have been previously mapped, showed that hydrophone-integrated AUVs could accurately map the location of soniferous fish over spatial scales of <1 km. The results show that passive acoustics is an effective, non-invasive tool to map the distribution of this species over large spatial scales.

Evaluation of pegylated lipid nanocapsules versus complement system activation and macrophage uptake.

This work consisted in defining the in vitro behavior of pegylated lipid nanocapsules (LNC) toward the immune system. LNC were composed of an oily core surrounded by a shell of lecithin and polyethylene glycol (PEG) known to decrease the recognition of nanoparticles by the immune system. The "stealth" properties were evaluated by measuring complement activation (CH50 technique and crossed-immunoelectrophoresis (C3 cleavage)) and macrophage uptake. These experiments were performed on 20-, 50-, and 100-nm LNC before and after dialysis. A high density of PEG at the surface led to very low complement activation by LNC with a slight effect of size. This size effect, associated to a dialysis effect in macrophage uptake, was due to differences in density and flexibility of PEG chains related to LNC curvature radius. Thanks to a high density, 660-Da PEG provided LNC a steric stabilization and a protective effect versus complement protein opsonization, but this protection decreased with the increase of LNC size, especially versus macrophage uptake.

Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR-direct sequencing approach.

Human papillomaviruses (HPV) are etiological agents of cervical cancer. In order to address clinical demand for HPV detection and sequence typing, mostly in pre-cancerous cervical lesions, we applied our two-tier PCR-direct sequencing (PCR-DS) approach based on the use of both MY09/MY11 and GP5 + /GP6 + sets of primers. We tested 691 pathological specimens, all of which were biopsies, 75% of which were diagnosed histologically as cervical intraepithelial neoplasia (CIN) grades I-III. In total, 484 samples (70%) tested HPV-positive, yielding 531 HPV sequences from 47 HPV types, including two novel types. Four most frequently found HPV types accounted for 52.9% of all isolates: HPV6, 16, 11, and 31 (21.5%, 20.0%, 7.0%, and 4.5%, respectively). Some interesting results are the following: all currently known high-risk HPV (14 types) and low-risk HPV (6 types) were detected; HPV18 was not the 1st or 2nd but rather the 4th-5th most frequent high-risk HPV type; the highest detection rate for HPV (86%) among samples suspected to be HPV-infected was found in the youngest age group (0-10 years old), including 70% (44/63) "genital" HPV types; HPV types of undetermined cervical cancer risk represented 19% and of the total HPV isolates but were strongly increased in co-infections (36.5% of all isolates). To our knowledge, this is the largest sequencing-based study of HPV. The HPV types of unknown cancer risk, representing the majority of the known HPV types, 27 of the 47 types detected in this study, are not likely to play a major role in cervical cancer because their prevalence in CIN-I, II, and III declines from 16% to 8% to 2.5%. The two-tier PCR-DS method provides greater sensitivity than cycle sequencing using only one pair of primers. It could be used in a simple laboratory setting for quick and reliable typing of known and novel HPV from clinical specimens with fine sequence precision. It could also be applied to anti-cancer vaccine development.

Pulmonary lymphangiectasia revisited.

PURPOSE: Pulmonary lymphangiectasia (PL) is a rare, poorly documented disease characterized by abnormal pulmonary lymphatics. Although case reports are published, little is known about survivors past the neonatal period. METHODS: This is a retrospective review of histologically proven PL in fetuses, infants, and long term survivors since 1965. RESULTS: Eleven children (8 boys, 3 girls) and 8 aborted fetuses (7 male, 1 female) were identified. The fetuses weighed 463.4 g (177 to 681 g). Six were aborted between 19 to 24 weeks of gestation for multiple malformations or anencephaly, and 2 spontaneously aborted: one with PL only, the other with twin-twin transfusion syndrome. Clinical PL was diagnosed between 0 and 11 months of age. Six children died (2 neonatal, 4 within 10 days), 5 survived. Two deaths occurred after cardiac surgery. Among survivors, the symptomatology and frequency of admissions diminished over time. Symptoms included progressive respiratory distress, chronic cough, recurrent pneumonia, bronchial asthma, and choking. One child with bilateral chylothorax was later diagnosed with Noonan syndrome; 2 patients had minor cardiac malformations. Rapid deterioration occurred with mild respiratory infections with only supportive treatment available. Chest x-ray showed marked hyperinflation with interstitial infiltrate. CONCLUSIONS: This is the first long-term study of primary PL and will help counsel parents. Although fatal in the neonatal period, survival is possible if diagnosed past the neonatal period and improvement is expected.

Prevalence of risk factors associated with human papillomavirus infection in women living with HIV. Canadian Women's HIV Study Group.

BACKGROUND: Concurrent infection with HIV and human papillomavirus (HPV) in women is associated with increased rates of cervical dysplasia and shorter survival following the development of cervical cancer. The authors examined risk factors for HPV infection at study entry in HIV-positive women enrolled in the Canadian Women's HIV Study, a prospective open cohort study. METHODS: Subjects eligible for this analysis included the 375 HIV-positive women in the Canadian Women's HIV Study for whom HPV test results were available. Questionnaires on behavioural and clinical information, Pap smears, cervicovaginal lavage specimens and vaginal tampon specimens for HPV detection and typing by polymerase chain reaction were obtained at study entry. RESULTS: Overall, 67.2% (252/375) of the women were HPV-positive; the global prevalence of intermediate- and high-risk oncogenic HPV types was 49.1% (184/375). Women with squamous cell dysplasia (32/294) were more likely to have HPV infection than those without dysplasia (90.6% v. 62.6%; p = 0.002). Multivariate logistic regression analysis, with adjustment for number of lifetime partners and history of STD, revealed that the following risk factors were independently associated with HPV infection: CD4 count of less than 0.20 x 10(9)/L (adjusted odds ratio [OR] 1.99 [95% confidence interval (Cl) 1.17-3.37 (p = 0.011)]), non-white race (adjusted OR 2.00 [95% Cl 1.17-3.42 (p = 0.011)]), inconsistent condom use in the 6 months before study entry (adjusted OR 2.02 [95% Cl 1.16-3.50 (p = 0.013)]), and lower age, with women age 30-39 years (adjusted OR 0.51 [95% Cl 0.30-0.87 (p = 0.013)]) and age 40 years or older (adjusted OR 0.52 [95% Cl 0.26-1.01 (p = 0.052)]) compared with women less than 30 years of age. INTERPRETATION: Close monitoring for HPV-related effects is warranted in all HIV-positive women, particularly younger, non-white women who do not always use condoms. Counselling for women living with HIV, particularly younger women, should emphasize the importance of regular cytological screening, with increasing frequency as the CD4 count falls.

Chronic obstructive pulmonary disease: capillarity and fiber-type characteristics of skeletal muscle.

BACKGROUND: The purpose of this investigation was to compare capillarity and fiber type proportions of the vastus lateralis muscle between patients with chronic obstructive pulmonary disease (COPD) and healthy subjects. METHODS: Fifteen male subjects were included in the study (8 COPD: 61.0 +/- 1.8 years [mean +/- SEM]; forced expiratory volume in 1 second 42.0 +/- 2.1% predicted; 7 N: age 54.0 +/- 1.1). Subjects were submitted to a symptom-limited maximal exercise test on ergocycle. After a transcutaneous biopsy of the vastus lateralis muscle, sections were cut 8 to 10 microns thick and stained with the Andersen method for capillarity and Stevens method for fiber typing. RESULTS: Patients with COPD had a decrease in peak oxygen consumption compared with healthy subjects (1.2 +/- 0.1 versus 3.0 +/- 0.2 L/min). Number of capillaries per square millimeter was lower in patients with COPD versus healthy subjects (92.6 +/- 16.1 and 213.3 +/- 33.5, P < 0.001); percentages of fiber types were 43.5 +/- 5.5% type I, 56.5 +/- 5.5% type II in COPD, and 56.7 +/- 3.4% type I, 43.2 +/- 3.4% type II in healthy subjects (P < 0.05). In addition, capillaries/fiber ratio was 0.83 +/- 0.05 in COPD, and 1.56 +/- 0.10 in healthy subjects (P < 0.001). CONCLUSION: As expected, patients with COPD showed a decrease in exercise capacity. The muscle analysis results indicate that patients with COPD have a greater proportion of type II fibers and a much lower capillaries/fiber ratio than normal subjects. We conclude that COPD adversely affects fiber type and capillarization of the lower limbs. This could be partly caused by deconditioning in these patients.

Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease.

PURPOSE AND METHODS: In this study, we examined the fiber-type proportions, cross-sectional areas (CSA), and capillarization from needle biopsies of the vastus lateralis muscle in 20 patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 37 +/- 11% predicted, peak VO2 = 13 +/- 4 mL.min-1.kg-1) and nine age-matched normal subjects (peak VO2 = 33 +/- 7 mL.min-1.kg-1). The effects of endurance training on these parameters were also evaluated in 11 of the 20 patients with COPD. RESULTS: The proportion of Type I fiber was smaller in COPD than normals (34 +/- 14% vs 58 +/- 16 in normals, P < 0.0005) with a corresponding increase in Type IIb fiber (P = 0.015). The CSA of Type I, IIa, and IIab fibers was also smaller in COPD. The capillary to fiber ratio tended to be reduced in patients, but this difference did not reach statistical significance (P = 0.15). The number of capillary contact for Type I, IIa, and IIab fibers was significantly reduced in COPD compared with normal subjects (P < 0.05). When corrected for the CSA, this parameter was similar for both groups. After training, peak VO2 increased by 11% (P < 0.05), the fiber-type proportion remained unchanged, and the CSA of Type I and IIa fibers increased by 31 and 21%, respectively (P < 0.05). Although the number of capillary contact for each fiber types increased with training, the capillary to fiber ratio and the number of capillary contact for the different fiber types relative to their CSA remain unchanged. CONCLUSIONS: We conclude that in COPD, 1) the vastus lateralis muscle is characterized by a marked decrease in Type I fiber proportion, an increase in Type IIb fiber proportion, a decrease in Type I, IIa, and IIab fiber CSA and by a relatively preserved capillarization; and 2) a 12-wk training program induces a significant increase in Type I and IIa CSA.

JC9813-A putative novel human papillomavirus identified by PCR-DS.

Papillomaviruses consist of more than 130 viral types described so far. Most of them are human papillomaviruses (HPV) of supergroup A, demonstrating ano-genital tropism and characterized as etiological agents for benign and malignant cervical lesions in women. A PCR-direct sequencing (PCR-DS) approach with P-33 labeled dideoxynucleotides was used to detect and type human papillomaviruses in cervical biopsies. One novel sequence was identified in a LSIL (low-grade squamous intraepithelial lesions) specimen from an HIV-positive English Canadian patient. The structure of the viral gene L1 was determined, yielding a putative novel HPV type of supergroup A (clade A8) named JC9813.

Assessing autonomy among Sahelian women: an analytical framework for women's production work.

PIP: This study assessed autonomy, control over food production, and craft activities among rural Bambara women in Mali. The study intended to show how the methodology is useful for analyzing how the different components of women's work are embedded within a set of social, economic, and environmental factors. Interviews were conducted among 111 women from Gagna, Siratinti, and Toun villages in Djenne region, and 3 Gagna men, 4 government workers, and 3 CARE and CUSO project coordinators. Interviews were conducted and observations made during August 1988 to March 1989, and in February 1990. Women cultivate the delta land, which has been affected by reduced rainfall and vegetation since the late 1960s. Women's production is affected by time, technical knowledge, and husband's permission. Control over garden work is measured by decision-making, control factors, and degree of control for land, water, seeds, access to a "daba", access to a pail, mission restrictions, know-how, time (in general), time for watering, women's physical ability, and produce (cotton, vegetables, and condiments). Women's autonomy is determined by types of factors, impact of factors, economic factors, environmental factors, scale, and relationships between men and women, between women, and between ethnic groups. Women have control over income to meet the family's needs. Neither men nor women control all the components of their gender-based work. Women must negotiate their access to raw materials and assistance. Help usually involves people from outside the husband's family. Non-family networks of friends provide support and services.^ieng

A two-tier polymerase chain reaction direct sequencing method for detecting and typing human papillomaviruses in pathological specimens.

An in-house polymerase chain reaction direct sequencing (PCR-DS) approach for HPV detection and typing was developed, taking advantage of two widely used pairs of human papillomavirus (HPV)-specific PCR primers, MY09/MY11 and GP5/GP6, and 33P-labeled dideoxynucleotides. In this study, 105 pathological specimens were examined: 89% were diagnosed as cervical intraepithelial neoplasia (CIN) grade I-III, 76.2% were HPV-positive by PCR-DS. The PCR using GP5/GP6 (first tier) and MY09/MY11 primers (second tier for the GP5/GP6-negative samples) detected additional 15%-25% HPV-positive samples compared with each pair used separately. Direct sequencing was then used to type the HPV. A readout of a sequence as short as 34 nucleotides within a specific region in the L1 gene is sufficient to type known or novel sequences. Because of its high sensitivity and cost-effectiveness, the two-tier PCR-DS was adopted by the authors as the current method of choice for HPV diagnosis with ultimate sequence precision.

Aeromonas hydrophila isolated from food and drinking water: hemagglutination, hemolysis, and cytotoxicity for a human intestinal cell line (HT-29).

Aeromonas hydrophila isolated from food and drinking water was tested for pathogenicity by studying its hemolysis, hemagglutination, and cytotoxicity. Hemolysis, tested on erythrocytes from six different species, was more frequently seen with water isolates (64%) than with food isolates (48%). Hemagglutination was more frequently encountered with food isolates (92%) than with water isolates (73%). Cytotoxicity, evaluated on seven cell lines, was frequently observed with food isolates (92%) and with water isolates (73%). Heat treatment (56 degrees C for 10 min) of culture supernatant fluids inhibited the toxicity of some but not all toxin-producing isolates. Our results suggest that the human intestinal cell line HT-29 could be a useful complement for testing A. hydrophila exotoxins and for studying the enteropathogenicity of this species for humans.

Differential media for quantitative recovery of waterborne Aeromonas hydrophila.

Because of the ubiquity of Aeromonas spp., their prevalence in drinking water, and the increasing number of reports on Aeromonas sp.-related infections, a standard method for routine and quantitative recovery had to be defined. On the basis of a survey of 10 media for recovery analysis and subsequent differentiation assays in mixed cultures, we conclude that ampicillin-dextrin agar performed the best for the recovery of Aeromonas spp. in drinking water and the differentiation by simple criteria of that genus from other common waterborne bacteria.

Evidence for functional interaction between the HIV-1 Tat transactivator and the TATA box binding protein in vivo.

Tat strongly activates transcription of the HIV-1 provirus by stimulating both initiation and elongation. This transactivator binds to the TAR RNA element, but can also associate with cellular transcription factors, interacting with upstream promoter sequences. To achieve a better understanding of the role of Tat in the assembly of the transcriptional initiation complex in the living cell, we have examined how the activity of this protein is modified when the general transcription factor involved in the first step of this process, TBP, is overexpressed. The activity of Tat, either wild-type or fused to the DNA binding domain of GAL4 (GBTat), was tested using reporter constructs containing GAL4 binding sites upstream of a minimal promoter corresponding to the HIV-1 TATA box, with or without the TAR element. We found that overexpression of TBP led to a dramatic increase in the activity of the GBTat protein. In order to activate GBTat, TBP must be able to interact with the TATA box. Analysis of several Tat mutants indicated that both the cysteine-rich and the core domains of this transactivator are necessary and sufficient to activate transcription when TBP is overexpressed. In vitro experiments showed that Tat binds specifically to TBP. There was a correlation between the ability of different Tat mutants to bind TBP and their capacity to activate transcription in vivo. With the natural HIV-1 promoter, overexpression of TBP first stimulated and then suppressed the Tat-induced activity. This inhibition was abrogated by an increase in the intracellular levels of Tat. These experimental data indicate that Tat stimulates initiation of transcription by interacting with TBP in vivo.

Characterization of beta 1- and beta 3-adrenoceptors in intact brown adipocytes of the rat.

1. The binding properties of beta 1-, beta 2- and beta 3-adrenoceptors were determined in isolated brown adipocytes of the rat rather than in membrane preparations from tissue homogenates, because typical brown adipocytes represent only about 40% of the various cells present in brown adipose tissue. Binding characteristics were assessed with the hydrophilic beta-adrenoceptor radioligand, (-)-[3H]-CGP 12177. The potent beta-antagonist, bupranolol (100 microM) was used to determine nonspecific binding. Characterization was essentially performed by saturation and competition studies. 2. The saturation curve of (-)-[3H]-CGP 12177 was clearly biphasic (Hill coefficient, nH = 0.57 +/- 0.11, P < 0.01) indicating the presence of two different beta-adrenoceptor populations of high (KD = 0.24 +/- 0.04 nM) and low (KD = 80 +/- 7 nM) affinity. The low affinity sites were more numerous (Bmax = 121,000 +/- 30,000 sites/cell) than the high affinity sites (Bmax = 12,000 +/- 1,000 sites/cell). 3. (-)-[3H]-CGP 12177 (25 nM) was displaced by adrenaline (Ad), noradrenaline (NA), isoprenaline (Iso), phenylephrine (Phe) and by the new beta 3 agonist, CL 316,243 (CL) in a biphasic pattern. The order of potency for (-)-[3H]-CGP 12177 displacement from the small population of high affinity sites (Iso >> NA > Ad >> CL >> Phe was in agreement with a beta 1/beta 2-classification. In contrast, the potencies of the same agonists for displacing the radioligand from the low affinity binding sites (CL >> Iso > NA > Ad >> Phe) revealed the presence of a distinct population of adrenoceptors obeying a beta 3-classification. 5-HT did not displace (-)-[3H]-CGP 12177 (25 nM) when used at concentrations as high as 0.1 mM.4. The beta-adrenoceptor antagonist, (-)-bupranolol, was more effective than (-)-propranolol for displacing(- )-[3H]-CGP 12177 (25 nM) from the high (Ki= 0.029 =/- 0.011 and 0.19 +/- 0.07 nM, respectively and low (Ki= 0.27 +/- 0.04 microM and 1.6 +/- 0.2 lM, respectively) affinity binding sites. The selective beta 1 antagonist CGP 20712A efficiently displaced the radioligand from a small population (Ki = 65 +/- 19 pM)of binding sites, confirming the presence of beta 1-adrenoceptors.5. To evaluate whether beta 2-adrenoceptors could be identified in the population of high affinity binding sites, displacement studies were performed at a low concentration of (- )-[3H]-CGP 12177 (4 nM) that mainly labelled beta 1/beta 2-adrenoceptors. ICI 118 551 ( a selective beta 2-antagonist) and procaterol (a selective beta 2-agonist) displaced (- )-[3H]-CGP 12177 from its binding sites with very low affinity (Ki = 0.17 +/- 0.02 micro M and Ki = 11 +/- 2 micro M respectively).6. From these observations, we conclude that: (1) two kinds of binding sites with low and high affinities for (-)-[H]-CGP 12177 can be detected in intact brown adipocytes, (2) there are 10 times more low than high affinity beta-adrenoceptors, as determined by saturation or competition curve analysis, (3) the high affinity binding sites mainly correspond to beta1-adrenoceptors, whereas the low affinity sites represent beta 3-adrenoceptors, and (4) beta 2-adrenoceptors are undetectable.7. It is suggested that the low affinity beta 3-adrenoceptors represent the physiological receptors for noradrenaline secreted from sympathetic nerve endings when the concentration of the neurohormone in the synaptic cleft is very high and/or when the high affinity beta 1-adrenoceptors are desensitized by prolonged sympathetic stimulation such as chronic cold exposure.

Comparison of the lipolytic effects of norepinephrine and BRL 37344 in rat brown and white adipocytes.

The lipolytic effects of norepinephrine (a non-selective beta-agonist) and BRL 37344 (a selective beta3-agonist) were compared in isolated rat brown and white adipocytes. Norepinephrine and BRL 37344 maximally stimulated lipolysis in brown and white adipocytes, approximately 10 times above basal values. However, adipocyte sensitivity for BRL 37344 was greater than that for norepinephrine, particularly in brown adipocytes [the EC50 values (nM) for BRL 37344 and norepinephrine were 5 +/- 1 and 103 +/- 31 in brown adipocytes (P < 0.01) versus 56 +/- 9 and 124 +/- 17 in white adipocytes (P < 0.05), respectively]. On the other hand, the lipolytic effects of norepinephrine were totally blocked by 20-40 times superior concentrations of propranolol or bupranolol in brown as well as in white adipocytes. In contrast, the lipolytic effects of BRL 37344 were fully inhibited by concentrations of propranolol or bupranolol that were 200-1000 superior to the beta3 agonist concentration. The results demonstrate that: (1) the beta3-agonist BRL 37344 is as effective as norepinephrine for maximally stimulating lipolysis in rat brown and white adipocytes, (2) both adipocyte types are more sensitive to the lipolytic effects of BRL 37344 than to those of norepinephrine, (3) although bupranolol is a better antagonist than propranolol on BRL 37344-stimulated lipolysis, it cannot be considered as a specific beta3-antagonist, (4) brown adipocytes are 10 times more sensitive than white adipocytes to the lipolytic effects of BRL 37344, suggesting an important role of beta3-receptors in brown adipose tissue.

Time is of the essence: a conjecture that hemispheric specialization arises from interhemispheric conduction delay.

Tomasch (1954) and Aboitiz et al. (1992) found the majority of the fibers of the human corpus callosum are under 1 micron in diameter. Electron microscopic studies of Swadlow et al. (1980) and the detailed study of LaMantia and Rakic (1990a) on macaques show the average size of the myelinated callosal axons also to be less than 1 micron. In man, the average-sized myelinated fiber interconnecting the temporal lobes would have a one-way, interhemispheric delay of over 25 msec. Thus, finely detailed, time-critical neuronal computations (i.e., tasks that strain the capacity of the callosum and hence could not be handled by just the larger fibers) would be performed more quickly via shorter and faster intrahemispheric circuits. While one transit across the commissural system might yield tolerable delays, multiple passes as in a system involving "setting" would seem prohibitively slow. We suggest that these temporal limits will be avoided if the neural apparatus necessary to perform each high-resolution, time-critical task is gathered in one hemisphere. If the, presumably overlapping, neural assemblies needed to handle overlapping tasks are clustered together, this would lead to hemispheric specialization. The prediction follows that the large brains of mammals such as elephants and cetaceans will also manifest a high degree of hemispheric specialization.

Comparison of the microbiological quality of water coolers and that of municipal water systems.

The microbiological quality of tap water and that of water from 50 water coolers located in residences and workplaces were comparatively studied. In addition, difference factors that might influence the bacteriological contamination of water dispensers were examined. Aeorbic and facultative anaerobic heterotrophic bacteria, total coliforms, and two indicators for fecal contamination (fecal coliforms and fecal streptococci) as well as three types of pathogenic bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Aeromonas spp.) were enumerated. It was found that 36 and 28% of the water dispenser samples from the residences and the workplaces, respectively, were contaminated by a least one coliform or indicator bacterium and/or at least one pathogenic bacterium. The respective proportions of tap water samples contaminated in a similar fashion were 18 and 22%, much less than those observed for water coolers (Chi2(1) = 3.71, P = 0.05). We were unable to discern the dominant factors responsible for the contamination of water coolers, but cleaning the water dispenser every 2 months seemed to limit the extent of contamination.

Learning long-term dependencies with gradient descent is difficult.

Recurrent neural networks can be used to map input sequences to output sequences, such as for recognition, production or prediction problems. However, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals. We show why gradient based learning algorithms face an increasingly difficult problem as the duration of the dependencies to be captured increases. These results expose a trade-off between efficient learning by gradient descent and latching on information for long periods. Based on an understanding of this problem, alternatives to standard gradient descent are considered.

The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene.

The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family. Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells. This activation was not observed in undifferentiated embryocarcinoma F9 cells. Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65. Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive. Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not. This established a clear difference between both stimuli, indicating that Rel is the functionally active factor. We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites.