Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein

Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional redundancy at the protein level gives the parasite phenotypic plasticity in the absence of differences in gene expression

Toward a complete theory for predicting inclusive deuteron breakup away from stability

We present an account of the current status of the theoretical treatment of inclusive $(d,p)$ reactions in the breakup-fusion formalism, pointing to some applications and making the connection with current experimental capabilities. Three independent implementations of the reaction formalism have been recently developed, making use of different numerical strategies. The codes also originally relied on two different but equivalent representations, namely the prior (Udagawa-Tamura, UT) and the post (Ichimura-Austern-Vincent, IAV) representations. The different implementations have been benchmarked, and then applied to the Ca isotopic chain. The neutron-Ca propagator is described in the Dispersive Optical Model (DOM) framework, and the interplay between elastic breakup (EB) and non-elastic breakup (NEB) is studied for three Ca isotopes at two different bombarding energies. The accuracy of the description of different reaction observables is assessed by comparing with experimental data of $(d,p)$ on $^{40,48}$Ca. We discuss the predictions of the model for the extreme case of an isotope ($^{60}$Ca) currently unavailable experimentally, though possibly available in future facilities (nominally within production reach at FRIB). We explore the use of $(d,p)$ reactions as surrogates for $(n,\gamma)$ processes, by using the formalism to describe the compound nucleus formation in a $(d,p\gamma)$ reaction as a function of excitation energy, spin, and parity. The subsequent decay is then computed within a Hauser-Feshbach formalism. Comparisons between the $(d,p\gamma)$ and $(n,\gamma)$ induced gamma decay spectra are discussed to inform efforts to infer neutron captures from $(d,p\gamma)$ reactions. Finally, we identify areas of opportunity for future developments, and discuss a possible path toward a predictive reaction theory

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

Dynamical dark energy: Current constraints and forecasts

We consider how well the dark energy equation of state $w$ as a function of red shift $z$ will be measured using current and anticipated experiments. We use a procedure which takes fair account of the uncertainties in the functional dependence of $w$ on $z$, as well as the parameter degeneracies, and avoids the use of strong prior constraints. We apply the procedure to current data from WMAP, SDSS, and the supernova searches, and obtain results that are consistent with other analyses using different combinations of data sets. The effects of systematic experimental errors and variations in the analysis technique are discussed. Next, we use the same procedure to forecast the dark energy constraints achieveable by the end of the decade, assuming 8 years of WMAP data and realistic projections for ground-based measurements of supernovae and weak lensing. We find the $2 \sigma$ constraints on the current value of $w$ to be $\Delta w_0 (2 \sigma) = 0.20$, and on $dw/dz$ (between $z=0$ and $z=1$) to be $\Delta w_1 (2 \sigma)=0.37$. Finally, we compare these limits to other projections in the literature. Most show only a modest improvement; others show a more substantial improvement, but there are serious concerns about systematics. The remaining uncertainty still allows a significant span of competing dark energy models. Most likely, new kinds of measurements, or experiments more sophisticated than those currently planned, are needed to reveal the true nature of dark energy.Comment: 24 pages, 20 figures. Added SN systematic uncertainties, extended discussio

Clinical and neural correlates of alexithymia in posttraumatic stress disorder.

Individuals with posttraumatic stress disorder (PTSD) often exhibit deficits in emotional experience and expression, which suggests that certain individuals with PTSD may be alexithymic. In this study, in a sample of 105 individuals with PTSD, clinical correlates of alexithymia included reexperiencing, hyperarousal, numbing, dissociative symptoms, and retrospectively reported experiences of childhood emotional neglect. In a subsample of 26 individuals with PTSD related to a motor vehicle accident, functional neural responses to trauma-script imagery were associated with severity of alexithymia, including increased right posterior-insula and ventral posterior-cingulate activation and decreased bilateral ventral anterior-cingulate, ventromedial prefrontal, anterior-insula, and right inferior frontal cortex activation. Clinical and theoretical implications and future research directions are discussed

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial.

BACKGROUND AND OBJECTIVE The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults'). METHODS Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness. RESULTS At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour. CONCLUSIONS In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg. Older patients particularly require this dose to improve daytime functioning. Older patients are not at an increased risk of adverse events or residual effects the next morning after night-time administration of daridorexant, even at 50 mg. The dose of daridorexant does not need to be decreased for older patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT03545191) [first posted: 4 June, 4 2018], https://clinicaltrials.gov/ct2/show/NCT03545191

Development of the (d,n) proton-transfer reaction in inverse kinematics for structure studies

Transfer reactions have provided exciting opportunities to study the structure of exotic nuclei and are often used to inform studies relating to nucleosynthesis and applications. In order to benefit from these reactions and their application to rare ion beams (RIBs) it is necessary to develop the tools and techniques to perform and analyze the data from reactions performed in inverse kinematics, that is with targets of light nuclei and heavier beams. We are continuing to expand the transfer reaction toolbox in preparation for the next generation of facilities, such as the Facility for Rare Ion Beams (FRIB), which is scheduled for completion in 2022. An important step in this process is to perform the (d,n) reaction in inverse kinematics, with analyses that include Q-value spectra and differential cross sections. In this way, proton-transfer reactions can be placed on the same level as the more commonly used neutron-transfer reactions, such as (d,p), (9Be,8Be), and (13C,12C). Here we present an overview of the techniques used in (d,p) and (d,n), and some recent data from (d,n) reactions in inverse kinematics using stable beams of 12C and 16O.Comment: 9 pages, 4 figures, presented at the XXXV Mazurian Lakes Conference on Physics, Piaski, Polan