Direct Visualization of the Human Estrogen Receptor α Reveals a Role for Ligand in the Nuclear Distribution of the Receptor

The human estrogen receptor α (ER α) has been tagged at its amino terminus with the S65T variant of the green fluorescent protein (GFP), allowing subcellular trafficking and localization to be observed in living cells by fluorescence microscopy. The tagged receptor, GFP-ER, is functional as a ligand-dependent transcription factor, responds to both agonist and antagonist ligands, and can associate with the nuclear matrix. Its cellular localization was analyzed in four human breast cancer epithelial cell lines, two ER+ (MCF7 and T47D) and two ER− (MDA-MB-231 and MDA-MB-435A), under a variety of ligand conditions. In all cell lines, GFP-ER is observed only in the nucleus in the absence of ligand. Upon the addition of agonist or antagonist ligand, a dramatic redistribution of GFP-ER from a reticular to punctate pattern occurs within the nucleus. In addition, the full antagonist ICI 182780 alters the nucleocytoplasmic compartmentalization of the receptor and causes partial accumulation in the cytoplasm in a process requiring continued protein synthesis. GFP-ER localization varies between cells, despite being cultured and treated in a similar manner. Analysis of the nuclear fluorescence intensity for variation in its frequency distribution helped establish localization patterns characteristic of cell line and ligand. During the course of this study, localization of GFP-ER to the nucleolar region is observed for ER− but not ER+ human breast cancer epithelial cell lines. Finally, our work provides a visual description of the “unoccupied” and ligand-bound receptor and is discussed in the context of the role of ligand in modulating receptor activity.

Forming classes by stimulus frequency: Behavior and theory

Visual classification is the way we relate to different images in our environment as if they were the same, while relating differently to other collections of stimuli (e.g., human vs. animal faces). It is still not clear, however, how the brain forms such classes, especially when introduced with new or changing environments. To isolate a perception-based mechanism underlying class representation, we studied unsupervised classification of an incoming stream of simple images. Classification patterns were clearly affected by stimulus frequency distribution, although subjects were unaware of this distribution. There was a common bias to locate class centers near the most frequent stimuli and their boundaries near the least frequent stimuli. Responses were also faster for more frequent stimuli. Using a minimal, biologically based neural-network model, we demonstrate that a simple, self-organizing representation mechanism based on overlapping tuning curves and slow Hebbian learning suffices to ensure classification. Combined behavioral and theoretical results predict large tuning overlap, implicating posterior infero-temporal cortex as a possible site of classification.

Distribution of planktonic foraminifera in surface sediments of the Mediterranean Sea

The Mediterranean Sea is a partillay isolated ocean where excess evaporation over precipitation results in large east to west gradients in temperature and salinity. Recent planktonic foraminiferal distributions have been examined in 66 surface sediment samples from the Mediterranean Sea. In addition to mapping the frequency distribution of 16 species, the faunal data has been subjected to cluster analysis, factor analysis and species diversity analysis. The clustering of species yields assemblages that are clearly temperature related. A warm assemblage contains both tropical and subtropical elements, while the cool assemblage can be subdivided into cool-subtropical, transitional and polar-subpolar groupings. Factor analysis is used to delineate the geographic distribution of four faunal assemblages. Factor 1 is a tropical-subtropical assemblage dominated by Globigerinoiden ruber. It has its highest values in the warmer eastern basin. Transitional species (Globorotalia inflata and Globigerina bulloides) dominate factor 2 with highest values occurring in the cooler western basin. Factor 3 reflects the distribution of Neogloboquadrina dutertrei and is considered to be salinity dependent. Subpolar species dominate factor 4 (Neoglobuquadrina pachyderma and G. bulloides), with highest values occurring in the northern part of the western basin where cold bottom water is presently being formed. The Shannon-Weiner index of species diversity shows that high diversity exists over much of the western basin and immediately east of the Strait of Sicily. This region is marked by equitable environmental conditions and relatively even distribution of individuals among the species. Conversely, in areas where temperature and salinity values are more extreme, diversity values are lower and the assemblages are dominated by one or two species.

Heart rate variability characterization using a time-frequency based instantaneous frequency estimation technique

In this paper, a new method for characterizing the newborn heart rate variability (HRV) is proposed. The central of the method is the newly proposed technique for instantaneous frequency (IF) estimation specifically designed for nonstationary multicomponen signals such as HRV. The new method attempts to characterize the newborn HRV using features extracted from the time–frequency (TF) domain of the signal. These features comprise the IF, the instantaneous bandwidth (IB) and instantaneous energy (IE) of the different TF components of the HRV. Applied to the HRV of both normal and seizure suffering newborns, this method clearly reveals the locations of the spectral peaks and their time-varying nature. The total energy of HRV components, ET and ratio of energy concentrated in the low-frequency (LF) to that in high frequency (HF) components have been shown to be significant features in identifying the HRV of newborn with seizures.

Regional flood frequency analysis for Newfoundland and Labrador using the L-Moments index-flood method

The L-moments based index-flood procedure had been successfully applied for Regional Flood Frequency Analysis (RFFA) for the Island of Newfoundland in 2002 using data up to 1998. This thesis, however, considered both Labrador and the Island of Newfoundland using the L-Moments index-flood method with flood data up to 2013. For Labrador, the homogeneity test showed that Labrador can be treated as a single homogeneous region and the generalized extreme value (GEV) was found to be more robust than any other frequency distributions. The drainage area (DA) is the only significant variable for estimating the index-flood at ungauged sites in Labrador. In previous studies, the Island of Newfoundland has been considered as four homogeneous regions (A,B,C and D) as well as two Water Survey of Canada's Y and Z sub-regions. Homogeneous regions based on Y and Z was found to provide more accurate quantile estimates than those based on four homogeneous regions. Goodness-of-fit test results showed that the generalized extreme value (GEV) distribution is most suitable for the sub-regions; however, the three-parameter lognormal (LN3) gave a better performance in terms of robustness. The best fitting regional frequency distribution from 2002 has now been updated with the latest flood data, but quantile estimates with the new data were not very different from the previous study. Overall, in terms of quantile estimation, in both Labrador and the Island of Newfoundland, the index-flood procedure based on L-moments is highly recommended as it provided consistent and more accurate result than other techniques such as the regression on quantile technique that is currently used by the government.

Longitudinal distribution and lateral pattern of megalopal settlement and juvenile recruitment of Carcinus maenas (L.) (Brachyura, Portunidae) in the Mira River Estuary, Portugal

Settlement is a critical process in the life history of crabs, and thus affecting the abundance, distribution and structure of estuarine communities. The spatial pattern of settlement of megalopae of the shore crab Carcinus maenas along a longitudinal estuarine gradient (Mira River Estuary, Portugal) was examined, as well as its effects on the juvenile population. To measure megalopal settlement, four replicate collectors were deployed in six equally spaced stations along the estuarine axis. Juveniles were collected on the same locations with a quadrat randomly deployed on the substrate. To assess fine-scale megalopal settlement within a curved region of the estuary, replicate collectors were deployed on both margins along Moinho da Asneira curve. Megalopae settled differently along the six longitudinal points, with a tendency to attenuate their settlement upstream. Within the curved region, megalopae preferentially settled on the left margin collectors, probably due to the weaker velocity speeds felt on this margin. Concerning the overall juvenile density, there were significant differences among the stations distributed along the estuary, but they did no reflect a longitudinal dispersion attenuation pattern. Size-frequency distribution of the juvenile population showed that the average size is higher on the left margin. Recruits (carapace length between 1.0 mm and 3.4 mm) were more abundant on the upstream stations. Density of early juveniles (3.4 mm-6.5 mm) and juveniles (6.5 mm-10 mm) was more stable throughout the estuary axis than that of recruits. This distribution pattern may result from tidal excursion processes or mechanisms to avoid biotic interactions, such as predation and competition. (c) 2006 Elsevier Ltd. All rights reserved.

Co-Infestation and Spatial Distribution of Bactrocera carambolae and Anastrepha spp. (Diptera: Tephritidae) in Common Guava in the Eastern Amazon.

Field infestation and spatial distribution of introduced Bactrocera carambolae Drew and Hancock and native species of Anastrepha in common guavas [Psidium guajava (L.)] were investigated in the eastern Amazon. Fruit sampling was carried out in the municipalities of Calc¸oene and Oiapoque in the state of Amapa, Brazil. The frequency distribution of larvae in fruit was fitted to the negative binomial distribution. Anastrepha striata was more abundant in both sampled areas in comparison to Anastrepha fraterculus (Wiedemann) and B. carambolae. The frequency distribution analysis of adults revealed an aggregated pattern for B. carambolae as well as for A. fraterculus and Anastrepha striata Schiner, described by the negative binomial distribution. Although the populations of Anastrepha spp. may have suffered some impact due to the presence of B. carambolae, the results are still not robust enough to indicate effective reduction in the abundance of Anastrepha spp. caused by B. carambolae in a general sense. The high degree of aggregation observed for both species suggests interspecific co-occurrence with the simultaneous presence of both species in the analysed fruit. Moreover, a significant fraction of uninfested guavas also indicated absence of competitive displacement.

What student attributes affect experience of PBL in Virtual Space?

Some Engineering Faculties are turning to the problem-based learning (PBL)paradigm to engender necessary skills and competence in their graduates. Since, at the same time, some Faculties are moving towards distance education, questions are being asked about the effectiveness of PBL for technical fields such as Engineering when delivered in virtual space. This paper outlines an investigation of how student attributes affect their learning experience in PBL courses offered in virtual space. A frequency distribution was superimposed on the outcome space of a phenomenographical study on a suitable PBL course to investigate the effect of different student attributes on the learning experience. It was discovered that the quality, quantity, and style of facilitator interaction had the greatest impact on the student learning experience. This highlights the need to establish consistent student interaction plans and to set, and ensure compliance with, minimum standards with respect to facilitation and student interactions.

Fast content-based file type identification

Digital forensic examiners often need to identify the type of a file or file fragment based only on the content of the file. Content-based file type identification schemes typically use a byte frequency distribution with statistical machine learning to classify file types. Most algorithms analyze the entire file content to obtain the byte frequency distribution, a technique that is inefficient and time consuming. This paper proposes two techniques for reducing the classification time. The first technique selects a subset of features based on the frequency of occurrence. The second speeds classification by sampling several blocks from the file. Experimental results demonstrate that up to a fifteen-fold reduction in file size analysis time can be achieved with limited impact on accuracy.

We still don’t know how much BPMN is enough – but we are getting closer

Process models expressed in BPMN typically rely on a small subset of all available symbols. In our 2008 study, we examined the composition of these subsets, and found that the distribution of BPMN symbols in practice closely resembles the frequency distribution of words in natural language. We offered some suggestions based on our findings, how to make the use of BPMN more manageable and also outlined ideas for further development of BPMN. Since this paper was published it has provoked spirited debate in the BPM practitioner community, prompted the definition of a modeling standard in US government, and helped shape the next generation of the BPMN standard.

Association between migraine and a functional polymorphism at the dopamine β-hydroxylase locus

Migraine is a common neurological disorder with a significant genetic component. Although a number of linkage and association studies have been undertaken, the number and identity of all migraine susceptibility genes has yet to be defined. The existence of dopaminergic hypersensitivity in migraine has been recognised on a pharmacological basis and some studies have reported genetic association between migraine and dopamine-related gene variants. Our laboratory has previously reported association of migraine with a promoter STR marker in the dopamine beta hydroxylase (DBH) gene. In the present study, we analysed two additional DBH markers in two independent migraine case–control cohorts. These two markers are putative functional SNPs, one within the promoter (−1021C→T) and another SNP (+1603C→T) in exon 11 of the DBH gene. The results showed a significant association for allelic and genotypic frequency distribution between the DBH marker in the promoter and migraine in the first (P = 0.004 and P = 0.012, respectively) and the second (P = 0.013 and P = 0.031, respectively) tested cohorts. There was no association observed between either genotype and/or allelic frequencies for the DBH marker located in exon 11 and migraine (P ≥ 0.05). The promoter DBH marker, reported associated with migraine in this study, has been shown to affect up to 52% of plasma DBH activity. Varying DBH activity levels have been postulated to be involved in migraine process with an increase of dopamine, resulting from a lower DBH activity shown positively correlated with migraine severity. It is plausible that the functional promoter variant of DBH may play a role in the migraine disorder.

Can estimates of antimalarial efficacy from field studies be improved?

Monitoring therapeutic efficacy of antimalarial drugs is important because treatment failure rates are the primary basis for changing antimalarial treatment policy. An important aspect of efficacy studies is the use of PCR genotyping to distinguish recrudescent from new infections. The conclusions reached using this technique might be misleading if there is insufficient parasite diversity or a non-uniform haplotype frequency distribution in the study area. Statistical techniques can be used to overcome this problem, but only when data describing the haplotype frequency distribution are available. Therefore, assessing haplotype frequency and distribution should form an integral part of all studies investigating the therapeutic efficacy of antimalarial treatment regimes.

Engineering Phenomenography

This chapter extends the phenomenographical research method by arguing the merits of engineering the outcome space from these investigations to effectively communicate the outcomes to an audience in technology-based discipline areas. Variations discovered from the phenomenographical study are blended with pre and post tests and a frequency distribution. Outcomes are then represented in a visual statistical manner to suit the specific target audience. This chapter provides useful insights that will be of interest to researchers wishing to present findings from qualitative research methods, and particularly the outcomes of phenomenographic investigations, to an audience in technology-based discipline areas.

Rainfall and streamflow response to El Niño Southern Oscillation: a case study in a semiarid catchment, Australia.

This paper aims to compare the shift in frequency distribution and skill of seasonal climate forecasting of both streamflow and rainfall in eastern Australia based on the Southern Oscillation Index (SOI) Phase system. Recent advances in seasonal forecasting of climate variables have highlighted opportunities for improving decision making in natural resources management. Forecasting of rainfall probabilities for different regions in Australia is available, but the use of similar forecasts for water resource supply has not been developed. The use of streamflow forecasts may provide better information for decision-making in irrigation supply and flow management for improved ecological outcomes. To examine the relative efficacy of seasonal forecasting of streamflow and rainfall, the shift in probability distributions and the forecast skill were evaluated using the Wilcoxon rank-sum test and the linear error in probability space (LEPS) skill score, respectively, at three river gauging stations in the Border Rivers Catchment of the Murray-Darling Basin in eastern Australia. A comparison of rainfall and streamflow distributions confirms higher statistical significance in the shift of streamflow distribution than that in rainfall distribution. Moreover, streamflow distribution showed greater skill of forecasting with 0-3 month lead time, compared to rainfall distribution.

Detection and characterisation of strong resistance to phosphine in Brazilian Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae)

As failure to control Rhyzopertha dominica (F.) with phosphine is a common problem in the grain-growing regions of Brazil, a study was undertaken to investigate the frequency, distribution and strength of phosphine resistance in R. dominica in Brazil. Nineteen samples of R. dominica were collected between 1991 and 2003 from central storages where phosphine fumigation had failed to control this species. Insects were cultured without selection until testing in 2005. Each sample was tested for resistance to phosphine on the basis of the response of adults to discriminating concentrations of phosphine (20 and 48 h exposures) and full dose-response assays (48 h exposure). Responses of the Brazilian R. dominica samples were compared with reference susceptible, weak-resistance and strong-resistance strains from Australia in parallel assays. All Brazilian population samples showed resistance to phosphine: five were diagnosed with weak resistance and 14 with strong resistance. Five samples showed levels of resistance similar to the reference strong-resistance strain. A representative highly resistant sample was characterised by exposing mixed-age cultures to a range of constant concentrations of phosphine for various exposure periods. Time to population extinction (TPE) and time to 99.9% suppression of population (LT99.9) values of this sample were generally similar to those of the reference strong-resistance strain. For example, at 0.1, 0.5 and 1.0 mg L-1, LT99.9 values for BR33 and the reference strong-resistance strain were respectively 21, 6.4 and 3.7 days and 17, 6.2 and 3.8 days. With both strains, doubling phosphine concentrations to 2 mg L -1 resulted in increased LT99.9 and TPE. High level and frequency of resistance in all population samples, some of which had been cultured without selection for up to 12 years, suggest little or no fitness deficit associated with phosphine resistance. The present research indicates that widespread phosphine resistance may be developing in Brazil. Fumigation practices should be monitored and resistance management plans implemented to alleviate further resistance development.