Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat

Calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and intermedin. Although CGRP is widely expressed in the nervous system, less is known about the localization of CLR and RAMP1. To localize these proteins, we raised antibodies to CLR and RAMP1. Antibodies specifically interacted with CLR and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western blotting and immunofluorescence. Fluorescent CGRP specifically bound to the surface of these cells and CGRP, CLR, and RAMP1 internalized into the same endosomes. CLR was prominently localized in nerve fibers of the myenteric and submucosal plexuses, muscularis externa and lamina propria of the gastrointestinal tract, and in the dorsal horn of the spinal cord of rats. CLR was detected at low levels in the soma of enteric, dorsal root ganglia (DRG), and spinal neurons. RAMP1 was also localized to enteric and DRG neurons and the dorsal horn. CLR and RAMP1 were detected in perivascular nerves and arterial smooth muscle. Nerve fibers containing CGRP and intermedin were closely associated with CLR fibers in the gastrointestinal tract and dorsal horn, and CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in the nervous system. However, mRNA encoding RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal horn, suggesting that CLR may associate with other RAMPs in these tissues to form a receptor for additional peptides such as adrenomedullin.

A characterization of the food industries

Consistent conjectures applied to the food industries are investigated. This is a homogeneous-product, quantity-setting model with identical firms. When firm numbers are fixed, the consistent conjecture is monopolistic. When variable, consistency requires firm output to expand with exit and contract with entry, but no conjecture exists that is consistent with equilibrium.

Direct observations of the evolution of polar cap ionization patches

Patches of ionization are common in the polar ionosphere where their motion and associated density gradients give variable disturbances to High Frequency (HF) radio communications, over-the-horizon radar location errors, and disruption and errors to satellite navigation and communication. Their formation and evolution are poorly understood, particularly under disturbed space weather conditions. We report direct observations of the full evolution of patches during a geomagnetic storm, including formation, polar cap entry, transpolar evolution, polar cap exit, and sunward return flow. Our observations show that modulation of nightside reconnection in the substorm cycle of the magnetosphere helps form the gaps between patches where steady convection would give a “tongue” of ionization (TOI).

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

Ice Shelf Water plume flow beneath Filchner-Ronne Ice Shelf, Antarctica

[1] A two-dimensional plume model is used to study the interaction between Filchner-Ronne Ice Shelf, Antarctica and its underlying ocean cavity. Ice Shelf Water (ISW) plumes are initiated by the freshwater released from a melting ice shelf and, if they rise, may become supercooled and deposit marine ice due to the pressure increase in the in situ freezing temperature. The aim of this modeling study is to determine the origin of the thick accretions of marine ice at the base of Filchner-Ronne Ice Shelf and thus improve our understanding of ISW flow paths. The model domain is defined from measurements of ice shelf draft, and from this ISW the model is able to predict plumes that exit the cavity in the correct locations. The modeled plumes also produce basal freezing rates that account for measured marine ice thicknesses in the western part of Ronne Ice Shelf. We find that the freezing rate and plume properties are significantly influenced by the confluence of plumes from different meltwater sources. We are less successful in matching observations of marine ice under the rest of Filchner-Ronne Ice Shelf, which we attribute primarily to this model’s neglect of circulations in the ocean outside the plume.

Identified consumers: an experiment on the informativeness of cross-demand price effects

Often, firms have no information on the specification of the true demand model they are faced with. It is, however, a well established fact that trial-and-error algorithms may be used by them in order to learn how to make optimal decisions. Using experimental methods, we identify a property of the information on past actions which helps the seller of two asymmetric demand substitutes to reach the optimal prices more precisely and faster. The property concerns the possibility of disaggregating changes in each product’s demand into client exit/entry and shift from one product to the other.

Control of final moisture content of food products baked in continuous tunnel ovens

There are well-known difficulties in making measurements of the moisture content of baked goods (such as bread, buns, biscuits, crackers and cake) during baking or at the oven exit; in this paper several sensing methods are discussed, but none of them are able to provide direct measurement with sufficient precision. An alternative is to use indirect inferential methods. Some of these methods involve dynamic modelling, with incorporation of thermal properties and using techniques familiar in computational fluid dynamics (CFD); a method of this class that has been used for the modelling of heat and mass transfer in one direction during baking is summarized, which may be extended to model transport of moisture within the product and also within the surrounding atmosphere. The concept of injecting heat during the baking process proportional to the calculated heat load on the oven has been implemented in a control scheme based on heat balance zone by zone through a continuous baking oven, taking advantage of the high latent heat of evaporation of water. Tests on biscuit production ovens are reported, with results that support a claim that the scheme gives more reproducible water distribution in the final product than conventional closed loop control of zone ambient temperatures, thus enabling water content to be held more closely within tolerance.

Using reanalysis data to quantify extreme wind power generation statistics : a 33 year case study in Great Britain

With a rapidly increasing fraction of electricity generation being sourced from wind, extreme wind power generation events such as prolonged periods of low (or high) generation and ramps in generation, are a growing concern for the efficient and secure operation of national power systems. As extreme events occur infrequently, long and reliable meteorological records are required to accurately estimate their characteristics. Recent publications have begun to investigate the use of global meteorological “reanalysis” data sets for power system applications, many of which focus on long-term average statistics such as monthly-mean generation. Here we demonstrate that reanalysis data can also be used to estimate the frequency of relatively short-lived extreme events (including ramping on sub-daily time scales). Verification against 328 surface observation stations across the United Kingdom suggests that near-surface wind variability over spatiotemporal scales greater than around 300 km and 6 h can be faithfully reproduced using reanalysis, with no need for costly dynamical downscaling. A case study is presented in which a state-of-the-art, 33 year reanalysis data set (MERRA, from NASA-GMAO), is used to construct an hourly time series of nationally-aggregated wind power generation in Great Britain (GB), assuming a fixed, modern distribution of wind farms. The resultant generation estimates are highly correlated with recorded data from National Grid in the recent period, both for instantaneous hourly values and for variability over time intervals greater than around 6 h. This 33 year time series is then used to quantify the frequency with which different extreme GB-wide wind power generation events occur, as well as their seasonal and inter-annual variability. Several novel insights into the nature of extreme wind power generation events are described, including (i) that the number of prolonged low or high generation events is well approximated by a Poission-like random process, and (ii) whilst in general there is large seasonal variability, the magnitude of the most extreme ramps is similar in both summer and winter. An up-to-date version of the GB case study data as well as the underlying model are freely available for download from our website: http://www.met.reading.ac.uk/~energymet/data/Cannon2014/.

Direct observations of the full Dungey convection cycle in the polar ionosphere for southward interplanetary magnetic field conditions

Tracking the formation and full evolution of polar cap ionization patches in the polar ionosphere, we directly observe the full Dungey convection cycle for southward interplanetary magnetic field (IMF) conditions. This enables us to study how the Dungey cycle influences the patches’ evolution. The patches were initially segmented from the dayside storm enhanced density plume at the equatorward edge of the cusp, by the expansion and contraction of the polar cap boundary due to pulsed dayside magnetopause reconnection, as indicated by in situ Time History of Events and Macroscale Interactions during Substorms(THEMIS) observations. Convection led to the patches entering the polar cap and being transported antisunward, while being continuously monitored by the globally distributed arrays of GPS receivers and Super Dual Auroral Radar Network radars. Changes in convection over time resulted in the patches following a range of trajectories, each of which differed somewhat from the classical twin-cell convection streamlines. Pulsed nightside reconnection, occurring as part of the magnetospheric substorm cycle, modulated the exit of the patches from the polar cap, as confirmed by coordinated observations of the magnetometer at Tromsø and European Incoherent Scatter Tromsø UHF radar. After exiting the polar cap, the patches broke up into a number of plasma blobs and returned sunward in the auroral return flow of the dawn and/or dusk convection cell. The full circulation time was about 3 h.

Basic Income, Republican Freedom, and Effective Market Power

This article examines republican arguments for a basic income that turn on a right to exit the labour market. It gives criteria for the maintenance of republican freedom in markets, arguing that a right to exit or effective market power will guarantee republican freedom in markets. The article then considers whether a basic income is either sufficient or necessary to protect republican freedom both in labour markets and elsewhere. If a basic income is necessary to protect republican freedom in the labour market, I argue it is not sufficient to protect that freedom elsewhere. If citizens lack the means to maintain their republican freedom in the labour market, then there may be other spheres of life where they are vulnerable to subordination, whether or not they have a basic income. Some sociological evidence on cultural consumption patterns is presented.

Internalization theory: an unfinished agenda

Internalization theory is usually applied at the firm level to analyse FDI, licensing and subcontracting, but this paper extends it to the industry level. It synthesises internalisation theory and oligopoly theory. It analyses a global industry where firms innovate competitively, and freely enter and exit the industry. It presents a formal model which highlights the inter-dependencies between rival firms. Each firm responds to its rivals by jointly optimising production and innovation through inter-dependent ownership and location decisions. The competitive outcome determines which firms serve which markets, which firms enter or exit the industry, and the internalisation strategy of each firm.

COMPOSITION OF SUPERCRITICAL CARBON DIOXIDE EXTRACTS OF PITANGA (EUGENIA UNIFLORA L.) LEAVES

The leaves of the Pitanga bush (Eugenia uniflora L.) are considered to be effective against many diseases. Extracts from Pitanga leaves have been found to show pronounced anti-inflammatory action and to have antimicrobial and antifungal activities, among other properties. In this work, extracts from Pitanga leaves were obtained by hydrodistillation and by extraction with supercritical carbon dioxide (SC-CO(2)) at three conditions of temperature and pressure. In the SC-CO(2) extractions also were collected the components that are lost with the CO(2) in the exit of the system using Porapak-Q polymer trap. All extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). Thirty-nine compounds were found in the extracts and twenty-six were identified. The main components identified in the extracts in decreasing quantitative order were: curzerene, germacrene B, C(15)H(20)O(2) and beta-elemene for hydrodistillation; C(15)H(20)O(2) and curzerene for SC-CO(2) extracts and 3-hexen-1-ol, curzerene, C(15)H(20)O(2), beta-elemene and germacrene B for SC-CO(2) extracts captured in Porapak-Q. PRACTICAL APPLICATIONS The natural extracts are a potential source of compounds possessing biological activities. They can be used in foods, pharmaceutics and cosmetics. Pitanga is an exotic fruit from Brazil and extracts from its leaves have been used against many diseases in Brazilian folk medicine. Supercritical extraction is an interesting process for the production of natural extracts because it is a clean process and the knowledge of composition of extracts is crucial for the identification of the probable active components.

Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies

A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 mu m analytical column (4.6 x 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1 mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 mu g/mL (r > 0.99). The limit of quantification was 0.1 mu g/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100 mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI = 88.16-99.79%) for C(max), 98.31% (90% CI = 94.91-101.83%) for AUC(last) and 97.67% (90% CI = 94.45-101.01%) for AUC(0-168 h). Since the 90% Cl for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless (R) 100 mg tablet) formulation manufactured by Biolab Sanus Farmaceutica Ltda. is bioequivalent to the Oroxadin (R) (100 mg tablet) formulation for both the rate and the extent of absorption. (C) 2011 Published by Elsevier B.V.

Plasmodium falciparum Accompanied the Human Expansion out of Africa

Plasmodium falciparum is distributed throughout the tropics and is responsible for an estimated 230 million cases of malaria every year, with a further 1.4 billion people at risk of infection [1-3]. Little is known about the genetic makeup of P. falciparum populations, despite variation in genetic diversity being a key factor in morbidity, mortality, and the success of malaria control initiatives. Here we analyze a worldwide sample of 519 P. falciparum isolates sequenced for two housekeeping genes (63 single nucleotide polymorphisms from around 5000 nucleotides per isolate). We observe a strong negative correlation between within-population genetic diversity and geographic distance from sub-Saharan Africa (R(2) = 0.95) over Africa, Asia, and Oceania. In contrast, regional variation in transmission intensity seems to have had a negligible impact on the distribution of genetic diversity. The striking geographic patterns of isolation by distance observed in P. falciparum mirror the ones previously documented in humans [4-7] and point to a joint sub-Saharan African origin between the parasite and its host. Age estimates for the expansion of P. falciparum further support that anatomically modern humans were infected prior to their exit out of Africa and carried the parasite along during their colonization of the world.

Temporal behaviour of toroidal rotation velocity in the TCABR tokamak

A new method for determining the temporal evolution of plasma rotation is reported in this work. The method is based upon the detection of two different portions of the spectral profile of a plasma impurity line, using a monochromator with two photomultipliers installed at the exit slits. The plasma rotation velocity is determined by the ratio of the two detected signals. The measured toroidal rotation velocities of C III (4647.4 angstrom) and C VI (5290.6 angstrom), at different radial positions in TCABR discharges, show good agreement, within experimental uncertainty, with previous results (Severo et al 2003 Nucl. Fusion 43 1047). In particular, they confirm that the plasma core rotates in the direction opposite to the plasma current, while near the plasma edge (r/a > 0.9) the rotation is in the same direction. This technique was also used to investigate the dependence of toroidal rotation on the poloidal position of gas puffing. The results show that there is no dependence for the plasma core, while for plasma edge (r/a > 0.9) some dependence is observed.