The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development.

Ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due to its varied and essential roles, free Ca(2+) is tightly regulated by complex mechanisms. These mechanisms are therefore of interest as putative drug targets. One pathway in Ca(2+) homeostatic control in apicomplexans uses a Ca(2+)/H(+) exchanger (a member of the cation exchanger family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised in asexual blood stage parasites. To determine the physiological importance of apicomplexan CAXs, tagging and knock-out strategies were undertaken in the genetically tractable T. gondii and P. berghei parasites. In addition, a yeast heterologous expression system was used to study the function of apicomplexan CAXs. Tagging of T. gondii and P. berghei CAXs (TgCAX and PbCAX) under control of their endogenous promoters could not demonstrate measureable expression of either CAX in tachyzoites and asexual blood stages, respectively. These results were consistent with the ability of parasites to tolerate knock-outs of the genes for TgCAX and PbCAX at these developmental stages. In contrast, PbCAX expression was detectable during sexual stages of development in female gametocytes/gametes, zygotes and ookinetes, where it was dispersed in membranous networks within the cytosol (with minimal mitochondrial localisation). Furthermore, genetically disrupted parasites failed to develop further from "round" form zygotes, suggesting that PbCAX is essential for ookinete development and differentiation. This impeded phenotype could be rescued by removal of extracellular Ca(2+). Therefore, PbCAX provides a mechanism for free living parasites to multiply within the ionic microenvironment of the mosquito midgut. Ca(2+) homeostasis mediated by PbCAX is critical and suggests plasmodial CAXs may be targeted in approaches designed to block parasite transmission

Heralded generation of entangled photon pairs

Entangled photons are a crucial resource for quantum communication and linear optical quantum computation. Unfortunately, the applicability of many photon-based schemes is limited due to the stochastic character of the photon sources. Therefore, a worldwide effort has focused in overcoming the limitation of probabilistic emission by generating two-photon entangled states conditioned on the detection of auxiliary photons. Here we present the first heralded generation of photon states that are maximally entangled in polarization with linear optics and standard photon detection from spontaneous parametric down-conversion. We utilize the down-conversion state corresponding to the generation of three photon pairs, where the coincident detection of four auxiliary photons unambiguously heralds the successful preparation of the entangled state. This controlled generation of entangled photon states is a significant step towards the applicability of a linear optics quantum network, in particular for entanglement swapping, quantum teleportation, quantum cryptography and scalable approaches towards photonics-based quantum computing

Paclitaxel alters the evoked release of calcitonin gene-related peptide from rat sensory neurons in culture

Peripheral neuropathy (PN) is a debilitating and dose-limiting side effect of treatment with the chemotherapeutic agent, paclitaxel. Understanding the effects of paclitaxel on sensory neuronal function and the signaling pathways which mediate these paclitaxel-induced changes in function are critical for the development of therapies to prevent or alleviate the PN. The effects of long-term administration of paclitaxel on the function of sensory neurons grown in culture, using the release of the neuropeptide calcitonin gene-related peptide (CGRP) as an endpoint of sensory neuronal function, were examined. Dorsal root ganglion cultures were treated with low (10 nM) and high (300 nM) concentrations of paclitaxel for 1, 3, or 5 days. Following paclitaxel treatment, the release of CGRP was determined using capsaicin, a TRPV1 agonist; allyl isothiocyanate (AITC), a TRPA1 agonist; or high extracellular potassium. The effects of paclitaxel on the release of CGRP were stimulant-, concentration-, and time-dependent. When neurons were stimulated with capsaicin or AITC, a low concentration of paclitaxel (10nM) augmented transmitter release, whereas a high concentration (300 nM) reduced transmitter release in a time-dependent manner; however, when high extracellular potassium was used as the evoking stimulus, all concentrations of paclitaxel augmented CGRP release from sensory neurons. These results suggest that paclitaxel alters the function of sensory neurons in vitro, and suggest that the mechanisms by which paclitaxel alters neuronal function may include functional changes in TRP channel activity. The described in vitro model will facilitate future studies to identify the signaling pathways by which paclitaxel alters neuronal sensitivity

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF

An assessment of the readiness of ablative materials for preflight application to the shuttle orbiter

The shuttle orbiter relies primarily on a reusable surface insulation (RSI) thermal protection system (TPS). The RSI is very efficient in its thermal performance; however, the RSI tile system has shown poor mechanical integrity. The state-of-the-art of the ablative TPS is reviewed, and an assessment made of the ablator's readiness for use on the shuttle orbiter. Unresolved technical issues with regard to the ablative TPS are identified. Short time, highly focused analytical and experimental programs were initiated to: (1) identify candidate ablation materials; (2) assess the data base for these materials; (3) evaluate the need and kind of waterproof coating; (4) calculate thermal and other stresses in an ablator tile; (5) identify an acceptable ablator/RSI tile joint filler; and (6) assess the sensitivity of the ablator to sequential heat pulses. Results from some of these programs are discussed

Stigmatizedâ Identity Cues: Threats as Opportunities for Consumer Psychology

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146893/1/jcpy1076_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146893/2/jcpy1076.pd

Violation of Bell's Inequality with Photons from Independent Sources

We report a violation of Bell's inequality using one photon from a parametric down-conversion source and a second photon from an attenuated laser beam. The two photons were entangled at a beam splitter using the post-selection technique of Shih and Alley [Phys. Rev. Lett. 61, 2921 (1988)]. A quantum interference pattern with a visibility of 91% was obtained using the photons from these independent sources, as compared with a visibility of 99.4% using two photons from a central parametric down-conversion source.Comment: 4 pages, 5 figures; minor change

Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events

Abstract Background In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. Patients and methods Patients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form. Results Treatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66–0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65–0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE. Conclusion In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE

24^{24}Mg(pp, α\alpha)21^{21}Na reaction study for spectroscopy of 21^{21}Na

The $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction was measured at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory in order to better constrain spins and parities of energy levels in $^{21}$Na for the astrophysically important $^{17}$F($\alpha, p$)$^{20}$Ne reaction rate calculation. 31 MeV proton beams from the 25-MV tandem accelerator and enriched $^{24}$Mg solid targets were used. Recoiling $^{4}$He particles from the $^{24}$Mg($p$, $\alpha$)$^{21}$Na reaction were detected by a highly segmented silicon detector array which measured the yields of $^{4}$He particles over a range of angles simultaneously. A new level at 6661 $\pm$ 5 keV was observed in the present work. The extracted angular distributions for the first four levels of $^{21}$Na and Distorted Wave Born Approximation (DWBA) calculations were compared to verify and extract angular momentum transfer.Comment: 11 pages, 6 figures, proceedings of the 18th International Conference on Accelerators and Beam Utilization (ICABU2014