Assessment of lake sensitivity to acidic deposition in national parks of the Rocky Mountains.

The sensitivity of high-elevation lakes to acidic deposition was evaluated in five national parks of the Rocky Mountains based on statistical relations between lake acid-neutralizing capacity concentrations and basin characteristics. Acid-neutralizing capacity (ANC) of 151 lakes sampled during synoptic surveys and basin-characteristic information derived from geographic information system (GIS) data sets were used to calibrate the statistical models. The explanatory basin variables that were considered included topographic parameters, bedrock type, and vegetation type. A logistic regression model was developed, and modeling results were cross-validated through lake sampling during fall 2004 at 58 lakes. The model was applied to lake basins greater than 1 ha in area in Glacier National Park (n = 244 lakes), Grand Teton National Park (n = 106 lakes), Great Sand Dunes National Park and Preserve (n = 11 lakes), Rocky Mountain National Park (n = 114 lakes), and Yellowstone National Park (n = 294 lakes). Lakes that had a high probability of having an ANC concentration <100 microeq/L, and therefore sensitive to acidic deposition, are located in basins with elevations >3000 m, with <30% of the catchment having northeast aspect and with >80% of the catchment bedrock having low buffering capacity. The modeling results indicate that the most sensitive lakes are located in Rocky Mountain National Park and Grand Teton National Park. This technique for evaluating the lake sensitivity to acidic deposition is useful for designing long-term monitoring plans and is potentially transferable to other remote mountain areas of the United States and the world.

Water and solute mass balance of five small, relatively undisturbed watersheds in the U.S.

Geochemical mass balances were computed for water years 1992-1997 (October 1991 through September 1997) for the five watersheds of the U.S. Geological Survey Water, Energy, and Biogeochemical Budgets (WEBB) Program to determine the primary regional controls on yields of the major dissolved inorganic solutes. The sites, which vary markedly with respect to climate, geology, physiography, and ecology, are: Allequash Creek, Wisconsin (low-relief, humid continental forest); Andrews Creek, Colorado (cold alpine, taiga/tundra, and subalpine boreal forest); Río Icacos, Puerto Rico (lower montane, wet tropical forest); Panola Mountain, Georgia (humid subtropical piedmont forest); and Sleepers River, Vermont (humid northern hardwood forest). Streamwater output fluxes were determined by constructing empirical multivariate concentration models including discharge and seasonal components. Input fluxes were computed from weekly wet-only or bulk precipitation sampling. Despite uncertainties in input fluxes arising from poorly defined elevation gradients, lack of dry-deposition and occult-deposition measurements, and uncertain sea-salt contributions, the following was concluded: (1) for solutes derived primarily from rock weathering (Ca, Mg, Na, K, and H(4)SiO(4)), net fluxes (outputs in streamflow minus inputs in deposition) varied by two orders of magnitude, which is attributed to a large gradient in rock weathering rates controlled by climate and geologic parent material; (2) the net flux of atmospherically derived solutes (NH(4), NO(3), SO(4), and Cl) was similar among sites, with SO(4) being the most variable and NH(4) and NO(3) generally retained (except for NO(3) at Andrews); and (3) relations among monthly solute fluxes and differences among solute concentration model parameters yielded additional insights into comparative biogeochemical processes at the sites.

Multi-MeV proton source investigations in ultraintense laser-foil interactions.

A study of the properties of multi-MeV proton emission from thin foils following ultraintense laser irradiation has been carried out. It has been shown that the protons are emitted, in a quasilaminar fashion, from a region of transverse size of the order of 100-200 microm. The imaging properties of the proton source are equivalent to those of a much smaller source located several hundred microm in front of the foil. This finding has been obtained by analyzing proton radiographs of periodically structured test objects, and is corroborated by observations of proton emission from laser-heated thick targets.

Macroscopic evidence of soliton formation in multiterawatt laser-plasma interaction.

A novel physical phenomenon has been observed following the interaction of an intense (10(19) W/cm(2)) laser pulse with an underdense plasma. Long-lived, macroscopic bubblelike structures have been detected through the deflection that the associated electric charge separation causes in a proton probe beam. These structures are interpreted as the remnants of a cloud of relativistic solitons generated in the plasma by the ultraintense laser pulse. This interpretation is supported by an analytical study of the soliton cloud evolution, by particle-in-cell simulations, and by a reconstruction of the proton-beam deflection.

Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin.

The structural characteristics of EMS1 (human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 gene is commonly amplified and overexpressed in several human cancers, which may alter their invasive or metastatic properties. An 80 to 85-kDa mobility shift of EMS1 correlates with an alteration in subcellular distribution and is likely to represent an important regulatory event. In HEK 293 cells, epidermal growth factor treatment or cell detachment induced this shift, and this was blocked by the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. Furthermore, expression of a constitutively active form of MEK induced the shift, indicating that MEK activation was both sufficient and necessary for this modification. The epidermal growth factor-induced shift correlated with increased phosphorylation on serine and threonine residues of the same tryptic phosphopeptides detected under basal conditions. Deletion of the helical-proline-rich region of the protein blocked the mobility shift and EMS1 phosphorylation. In vitro kinase assays demonstrated that the extracellular signal-regulated kinases represent candidate kinases for this region, although other MEK-regulated enzymes must also participate. These data identify MEK as an important intermediate involved in EMS1 phosphorylation and highlight the helical-proline-rich region as a key regulatory domain.

EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival.

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.

Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3.

Heregulin-mediated activation of particular erbB receptor combinations was used as a model system to investigate the interaction of erbB3 and erbB4 with the adaptor protein growth factor receptor-bound (Grb)7. In human breast cancer cell lines, co-immunoprecipitation of Grb7 with both receptors was detected upon heregulin stimulation. This association was direct and mediated by the Grb7 Src homology (SH)2 domain. Co-expression of erbB2 with erbB3 point mutants was used to map Grb7 binding sites. This demonstrated that tyrosine 1180 and 1243 represent the major and minor sites of Grb7 interaction, respectively. Although these recognition sequences possess an Asn residue at +2 relative to the phosphotyrosine and therefore represent potential Grb2 binding sites, phosphopeptide competition and "pull-down" experiments demonstrated that they interact preferentially with the Grb7 versus the Grb2 SH2 domain. Substitution analysis indicated that an Arg residue at +3 could act as a selectivity determinant, but the effect was context-dependent. Consequently, the Grb2 and Grb7 SH2 domains possess overlapping, but distinct, specificities. These studies therefore identify Grb7 as an in vivo target of erbB3 and erbB4 and provide an underlying mechanism for the ability of erbB3 to recruit Grb7 and not Grb2, a property unique among erbB receptors.

EMS1 amplification can occur independently of CCND1 or INT-2 amplification at 11q13 and may identify different phenotypes in primary breast cancer.

Chromosome 11q13 is amplified in about 13% of primary breast cancers. CCND1, encoding the cell cycle regulatory gene cyclin D1, and EMS1, encoding a filamentous actin binding protein, are favoured candidate onocogenes, whereas INT-2 is an unexpressed gene at this locus. In this study we tested the possibility that different regions of this large amplicon could be independently amplified and subsequently defined the phenotype of EMS1 amplified tumours in a series of 961 primary breast carcinomas. Using DNA slot blots, EMS1 was amplified in 15.2% of samples: 5.4% were coamplified for CCND1; 7.9% coamplified for INT-2 and 6.7% showed EMS1 amplification alone. The degree of amplification of CCND1 and INT-2 was highly correlated (P =0.0001). In contrast, no such relationship existed between EMS1 and CCND1 or INT-2 amplification, demonstrating independent amplification of EMS1 in 44% of amplified tumours. EMS1 amplification (> or = twofold increase in copy number) was positively correlated with patient age > or = 50 years (P = 0.025), ER positivity (P = 0.022), PgR positivity (P = 0.018), and was negatively correlated with HER-2/neu (c-erbB2) amplification (P = 0.01). In common with CCND1/INT-2, EMS1 amplification was associated with increased risk of relapse in patients with lymph node-negative disease (P = 0.028). In contrast, EMS1 and CCND1/INT-2 amplification appeared to confer different phenotypes in ER positive and negative tumours. A > or = threefold increase in EMS1 copy number was associated with an apparent increased risk of relapse and death in patients with ER negative tumours, but was without effect in ER positive tumours. In contrast, CCND1/INT-2 amplification had no effect in the patients with ER negative tumours but was associated with early relapse in ER positive patients. Thus EMS1 amplification may identify subgroups of breast cancer patients with increased probability of relapse and death distinct from those identified by CCND1/INT-2 amplification. Further studies are required to more clearly determine the functional consequences of EMS1 overexpression and a biological basis for the relationship between EMS1 amplification and phenotype in breast cancer.

Expression and tyrosine phosphorylation of EMS1 in human breast cancer cell lines.

The EMS1 gene encodes an 80/85 kDa c-src substrate and localises with the CCND1 gene to chromosome 11q13. This locus is amplified in approximately 13% of human breast cancers. EMS1 gene amplification and expression were characterised in a panel of human breast cancer cell lines to determine at what levels expression is regulated. The degree of tyrosine phosphorylation of EMS1 protein was also determined and compared with the activity of src-family kinases. The EMS1 gene was amplified in 6 of 20 cell lines investigated: MDA-MB-134, -157, -175, -453, ZR-75-1 and MCF-7. In the MDA-MB-157 and MCF-7 cell lines, EMS1 was amplified in the absence of CCND1 gene amplification. EMS1 protein levels were increased relative to normal breast epithelial cells in 6 cell lines (ZR-75-1, MDA-MB-134, -175, 453, MCF-7 and BT-474). Of these, BT-474 is the only cell line that does not exhibit EMS1 amplification or increased EMS1 mRNA levels. EMS1 tyrosine phosphorylation was 3-fold higher in BT-474 and T-47D cells, which exhibited relatively high total src activity coupled with expression of both c-fyn and c-yes, than in MDA-MB-453 cells, which expressed only c-yes. Our results therefore demonstrate gene amplification to be the predominant mechanism underlying EMS1 over-expression in human breast cancer cell lines and identify tyrosine phosphorylation as a further level at which regulation of this protein may be perturbed.

Hepatitis B vaccination rates among staff at a district general hospital.

OBJECTIVE: To evaluate the uptake of hepatitis B vaccination by staff of a metropolitan district general hospital and associated community health service in order to determine if the existing vaccination program was adequate. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey of all 1464 staff of a 304-bed district general hospital and associated community health service, serving a population of approximately 240,000 people in a middle socioeconomic area of northern Sydney, by means of a self-reported anonymous questionnaire. RESULTS: The overall response rate was 56.4%, with 61.9% of high-risk and 48.7% of low-risk staff responding to the survey. The overall vaccination rate was 55.8%. Of high-risk respondents, 70.7% had been or were in the process of being vaccinated, compared with 29.4% of low-risk respondents. Of those already vaccinated, only 45.9% had subsequently been tested for antibody to hepatitis B surface antigen (anti-HBs); 12% of this group did not know whether their response to the vaccine had been adequate and 18% reported being advised to have another anti-HBs test later. Vaccination rates were higher in younger staff (68.7% of 20-29-year-olds) than in older staff (42.7% of 50-59-year-olds). There was no significant difference in vaccination rates between men (55.6%) and women (55.8%). Vaccination rates for doctors, dentists and nurses were 69%, 80% and 74.6%, respectively. CONCLUSION: The vaccination rate among high-risk staff is suboptimal: more than half did not know whether their vaccination had induced a suitable level of antibodies; more than 10% had been vaccinated more than five years previously; and 5% had not completed the full course of three injections. High-risk staff should be targeted in future vaccination programs.

Parallel processing in rabbit first (SI) and second (SII) somatosensory cortical areas: effects of reversible inactivation by cooling of SI on responses in SII.

1. Previous observations on the effect of ablation or inactivation of the primary somatosensory cortex (SI) on the responses of neurons within the second somatosensory area (SII) to tactile stimuli point to profound differences between monkeys and certain other mammals in the organization of thalamocortical systems. In the cat, for example, tactile information appears to be conveyed in parallel from the thalamus to both SI and SII, whereas, in macaque and marmoset monkeys, it is conveyed in a serial (or hierarchical) scheme from the thalamus to SI and thence to SII. The present study examined the responses of individual SII neurons during reversible, cooling-induced inactivation of SI in another nonprimate placental mammal, the rabbit, to obtain further evidence on whether the above differences might reflect a fundamental distinction between simian primates and other mammalian species. 2. When the temperature at the face of a silver cooling block over the forepaw and hindpaw regions of SI was lowered to 5-13 degrees C, the SI surface potentials evoked by brief tactile stimuli were abolished (indicative of SI inactivation), whereas SII potentials remained intact. 3. The responses of 25 SII neurons to controlled tactile stimuli (consisting of 1- to 1.5-s trains of vibration or rectangular mechanical pulses) were studied before, during, and after inactivation of SI. The effects on the spontaneous activity of a further three SII neurons that lacked identified receptive fields were also studied. 4. The response or activity levels of 26 of the 28 SII neurons examined (93%) were unaffected by SI inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B infection of children in a mixed-race community in western New South Wales.

A seroprevalence survey of markers of hepatitis B virus (HBV) infection in children aged 0-16 years was conducted in a mixed-race township in western New South Wales. A total of 408 children were screened representing 95% of the total 0-16-year-old population. Of the Aboriginal subjects, 69% had seromarkers which indicated previous infection with HBV and 14% were hepatitis B surface antigen (HBsAg) seropositive. In the non-Aboriginal subjects the prevalence of seromarkers was 10% with no subjects HBsAg positive. The township provided an ideal setting for studying possible crossinfection from children in a high risk (Aboriginal) population group to children in a low-risk (non-Aboriginal) group. The ratio of children in the high-risk group for HBV infection to those in the low-risk group was approximately 2.7:1. Although HBsAg was highly endemic in the Aboriginal population, the data indicate that little crossinfection has occurred. We conclude that in this and similar mixed-race communities action should be taken to accelerate vaccination programmes aimed at reducing HBV infection among neonates and children in the high-risk groups. This will provide an immediate overall reduction of potential risk to both high-risk and low-risk groups while the issue of universal vaccination is considered further.

The prevalence of markers of infection with hepatitis B virus in a mixed-race Australian community.

A seroepidemiological study of markers of infection with hepatitis B virus was conducted in Brewarrina, a mixed-race township in north-western New South Wales. Six hundred and forty-three subjects, who represented 41.5% of the town's population, were screened for a range of serological markers of hepatitis B virus infection. Of the Aboriginal subjects, 72% had markers which indicated previous infection with hepatitis B virus, with 19.2% of subjects being identified as hepatitis B surface antigen (HBsAg)-seropositive. In the non-Aboriginal subjects, the prevalence of infection with markers of hepatitis B virus was 13.1%, with 2.2% of subjects being HBsAg-seropositive. The marker prevalences for Aboriginal and non-Aboriginal subjects in the 15- to 19-year-old age-group were 86.7% and 28%, respectively. The prevalence of hepatitis B virus infection in the total non-Aboriginal sample was higher than it is in the general Australian blood-donor population. The extent to which hepatitis B virus infection may result from cross-infection between coexisting "high-risk" and "low-risk" population groups is speculative. Furthermore, the risk of infection to non-Aborigines is unlikely to be spread evenly across the non-Aboriginal community. The cost of vaccine remains high, and until further data become available, mass vaccination of the population probably is not warranted. Initially, control measures should concentrate on the reduction of hepatitis B virus infection in the Aboriginal population and in non-Aboriginal households which contain a HBsAg-seropositive member.

Non-reinforcing effects of giving 'dessert' in rats.

We investigated in rats whether giving a sweet substance following a food (a 'dessert') would reinforce a preference for that food. The sweet substance had the reverse effect--rats preference for a flavor decreased if the flavor was given in a food preceding a sweet substance (saccharin or sucrose). If the substances were given in the reverse order, so the sweet substance preceded the food, the rats preferred a sweet substance that had been followed by food to one that had not been followed by food. We suggested two hypotheses to account for the data. Perhaps the sweet substance elicits a negative reaction that is unpleasant unless food is given. Thus, food following a sweet substance is reinforcing, while a sweet substance following food is not. A not incompatible alternative is that anticipatory contrast or comparison effects are involved. Assuming the sweet substance is preferred to the non-sweet, following food by a sweet substance could make the food less valued (anticipatory negative contrast), whereas following a sweet substance by food could make the sweet substance more valued (anticipatory positive contrast).

Conditioned flavor preferences based on delayed caloric consequences.

In four experiments we showed that rats prefer a flavor associated with a delayed edible consequence if the delayed consequence contains calories; the greater the number of calories, the greater the preference. We obtained conditioned preferences with delayed consequences of dextrose plus quinine, 8% polycose, 8% sucrose, 10 g of high fat mash, and 14 g of lab chow. No conditioned preferences were obtained with delayed consequences of saccharin, 10 g of low fat mash, 1% polycose, or 1% sucrose. Thus, it seems that flavor preferences based on delayed caloric consequences occur only if there are appreciable calories in the consequence.

Laser-induced fluorescence in high pressure solid propellant flames.

The application of laser-induced fluorescence (LIF) to the study of high pressure solid propellant flames is described. The distribution of the OH and CN radicals was determined in several solid propellant flames at pressures up to 3.5 MPa. The greatest difficulty in these measurements was the separation of the desired LIF signals from the large scattering at the laser wavelength from the very optically thick propellant flames. Raman experiments using 308-nm excitation were also attempted in the propellant flames but were unsuccessful due to LIF interferences from OH and NH.