Voltage-dependent Block of the Cystic Fibrosis Transmembrane Conductance Regulator Cl- Channel by Two Closely Related Arylaminobenzoates

The gene defective in cystic fibrosis encodes a Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is blocked by diphenylamine-2-carboxylate (DPC) when applied extracellularly at millimolar concentrations. We studied the block of CFTR expressed in Xenopus oocytes by DPC or by a closely related molecule, flufenamic acid (FFA). Block of whole-cell CFTR currents by bath-applied DPC or by FFA, both at 200 µM, requires several minutes to reach full effect. Blockade is voltage dependent, suggesting open-channel block: currents at positive potentials are not affected but currents at negative potentials are reduced. The binding site for both drugs senses ~40% of the electric field across the membrane, measured from the inside. In single-channel recordings from excised patches without blockers, the conductance was 8.0 ± 0.4 pS in symmetric 150 mM Cl^-. A subconductance state, measuring ~60% of the main conductance, was often observed. Bursts to the full open state lasting up to tens of seconds were uninterrupted at depolarizing membrane voltages. At hyperpolarizing voltages, bursts were interrupted by brief closures. Either DPC or FFA (50 µM) applied to the cytoplasmic or extracellular face of the channel led to an increase in flicker at V_m =-100 mV and not at V_m = +100 mV, in agreement with whole-cell experiments. DPC induced a higher frequency of flickers from the cytoplasmic side than the extracellular side. FFA produced longer closures than DPC; the FFA closed time was roughly equal (~ 1.2 ms) at -100 mV with application from either side. In cell-attached patch recordings with DPC or FFA applied to the bath, there was flickery block at V_m = -100 mV, confirming that the drugs permeate through the membrane to reach the binding site. The data are consistent with the presence of a single binding site for both drugs, reached from either end of the channel. Open-channel block by DPC or FFA may offer tools for use with site-directed mutagenesis to describe the permeation pathway

The effect of environmental variability on livestock and land-use management: The Borana plateau, southern Ethiopia

The Borana people are the predominant ethnic group on the Borana Plateau in southern Ethiopia. Though traditionally transhumant pastoralists, they have recently increased their reliance on crops. Rainfall in the region averages between 353 mm to 873 mm; variability in rainfall is quite high, with coefficients of variation ranging from.21 to.68. The past decade has witnessed a dramatic increase in land allocated to crops, and land in pastures that are either becoming privatised, or accessible to only a small sub-group of people. In this paper, we derive an empirical model of stocking rates and land allocation, which is then used to estimate the effects of exogenous parameters on stocking densities, land allocated to crops, and land allocated to private pastures. Results indicate the following: a) regions with high coefficients of variation in rainfall have lower livestock densities and less land allocated to crops, b) communities with greater numbers of households and higher population densities have larger indices of non-cooperation, higher stock densities, and more land allocated to crops, c) heterogeneity within a community, measured by the distribution of wealth levels, is positively related to an index of non-cooperation, and to higher stock densities, d) higher relative prices of livestock and shorter distances to market are associated with greater stock densities as well as greater land allocated to crops, e) the greater is mobility into an area, the higher are stock densities, and the lower is the cooperation level, whereas outward mobility by community members has no effect on either stock densities or the level of cooperation reached, f) the proportion of members engaged in wage work outside has a significant negative effect on the ability of the community to cooperate. Outside wage work also increases land allocated to crops, but has a significant negative effect on land allocated to private pastures, and g) the greater is the index of non-cooperation, the higher are stock densities and the greater is land allocated to crops.

Effective Radii and Color Gradients in Radio Galaxies

We present de Vaucouleurs' effective radii in B and R bands for a sample of Molonglo Reference Catalogue radio galaxies and a control sample of normal galaxies. We use the ratio of the scale lengths in the two bands as an indicator to show that the radio galaxies tend to have excess of blue color in their inner region much more frequently than the control galaxies. We show that the scale length ratio is a useful indicator of radial color variation even when the conventional color gradient is too noisy to serve the purpose.Comment: 11 pages, 4 figures, (LaTeX: aaspp4, epsfig), to appear in ApJL 199

Optimality Theory as a Framework for Lexical Acquisition

This paper re-investigates a lexical acquisition system initially developed for French.We show that, interestingly, the architecture of the system reproduces and implements the main components of Optimality Theory. However, we formulate the hypothesis that some of its limitations are mainly due to a poor representation of the constraints used. Finally, we show how a better representation of the constraints used would yield better results

On the relationship between cooling flows and bubbles

A common feature of the X-ray bubbles observed in Chandra images of some cooling flow clusters is that they appear to be surrounded by bright, cool shells. Temperature maps of a few nearby luminous clusters reveal that the shells consist of the coolest gas in the clusters—much cooler than the surrounding medium. Using simple models, we study the effects of this cool emission on the inferred cooling flow properties of clusters. We find that the introduction of bubbles into model clusters that do not have cooling flows results in temperature and surface brightness profiles that resemble those seen in nearby cooling flow clusters. They also approximately reproduce the recent XMM-Newton and Chandra observations of a high minimum temperature of ~1-3 keV. Hence, bubbles, if present, must be taken into account when inferring the physical properties of the intracluster medium. In the case of some clusters, bubbles may account entirely for these observed features, calling into question their designation as clusters with cooling flows. However, since not all nearby cooling flow clusters show bubble-like features, we suggest that there may be a diverse range of physical phenomena that give rise to the same observed features

Transferring Dense Pose to proximal animal classes

Recent contributions have demonstrated that it is possible to recognize the pose of humans densely and accurately given a large dataset of poses annotated in detail. In principle, the same approach could be extended to any animal class, but the effort required for collecting new annotations for each case makes this strategy impractical, despite important applications in natural conservation, science and business. We show that, at least for proximal animal classes such as chimpanzees, it is possible to transfer the knowledge existing in dense pose recognition for humans, as well as in more general object detectors and segmenters, to the problem of dense pose recognition in other classes. We do this by (1) establishing a DensePose model for the new animal which is also geometrically aligned to humans (2) introducing a multi-head R-CNN architecture that facilitates transfer of multiple recognition tasks between classes, (3) finding which combination of known classes can be transferred most effectively to the new animal and (4) using self-calibrated uncertainty heads to generate pseudo-labels graded by quality for training a model for this class. We also introduce two benchmark datasets labelled in the manner of DensePose for the class chimpanzee and use them to evaluate our approach, showing excellent transfer learning performance

Cytokine Profiles of Stimulated Blood Lymphocytes in Asthmatic and Healthy Adolescents Cross the School Year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-γ (IFN-γ), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th 1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-γ:IL-4 and IFN-γ:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation