Comparison of the absolute and relative efficiencies of electroporation-based transfection protocols for Plasmodium falciparum.

BACKGROUND: Several electroporation protocols exist to transfect exogenous DNA into Plasmodium falciparum. To date, however, only a subjective analysis of their relative efficiencies has been reported. METHODS: A time-course of luciferase reporter expression is used to provide an objective quantitative analysis of the absolute efficiency of three electroporation techniques; direct electroporation of ring stage infected erythrocytes, preloading of erythrocytes and a novel "double-tap" protocol that combines both approaches. RESULTS: Preloading of erythrocytes shows a mean efficiency of 9.59 x 10(-6), some 5-180 fold more efficient than matched experiments utilizing the "double-tap" and direct electroporation of ring stage infected erythrocytes alone, respectively. CONCLUSION: Evidence presented here provides the first quantitative assessment of both the absolute and relative efficiencies of a key molecular tool used to study the biology and pathogenesis of this important human pathogen

Evaluation of bioluminescence-based assays of anti-malarial drug activity

Transgenic Plasmodium falciparum expressing luciferase offers an attractive bioluminescence-based assay platform for the investigation of the pharmacological properties of anti-malarial drugs. Here a side-by-side comparison of bioluminescence and fluorescence-based assays, utilizing a luciferase reporter cassette that confers a strong temporal pattern of luciferase expression during the S-phase of intraerythrocytic development, is reported

Testing Superstring Theories with Gravitational Waves

We provide a simple transfer function that determines the effect of an early matter dominated era on the gravitational wave background and show that a large class of compactifications of superstring theory might be tested by observations of the gravitational wave background from inflation. For large enough reheating temperatures > 10^9 \GeV the test applies to all models containing at least one scalar with mass < 10^{12}\GeV that acquires a large initial oscillation amplitude after inflation and has only gravitational interaction strength, i.e., a field with the typical properties of a modulus.Comment: 5 pages 2 figures, v2: changes in presentation, refs revised, matches version in print in PR

Dark Radiation and Dark Matter in Large Volume Compactifications

We argue that dark radiation is naturally generated from the decay of the overall volume modulus in the LARGE volume scenario. We consider both sequestered and non-sequestered cases, and find that the axionic superpartner of the modulus is produced by the modulus decay and it can account for the dark radiation suggested by observations, while the modulus decay through the Giudice-Masiero term gives the dominant contribution to the total decay rate. In the sequestered case, the lightest supersymmetric particles produced by the modulus decay can naturally account for the observed dark matter density. In the non-sequestered case, on the other hand, the supersymmetric particles are not produced by the modulus decay, since the soft masses are of order the heavy gravitino mass. The QCD axion will then be a plausible dark matter candidate.Comment: 27 pages, 4 figures; version 3: version published in JHE

Gravitino Dark Matter in Tree Level Gauge Mediation with and without R-parity

We investigate the cosmological aspects of Tree Level Gauge Mediation, a recently proposed mechanism in which the breaking of supersymmetry is communicated to the soft scalar masses by extra gauge interactions at the tree level. Embedding the mechanism in a Grand Unified Theory and requiring the observability of sfermion masses at the Large Hadron Collider, it follows that the Lightest Supersymmetric Particle is a gravitino with a mass of the order of 10 GeV. The analysis in the presence of R-parity shows that a typical Tree Level Gauge Mediation spectrum leads to an overabundance of the Dark Matter relic density and a tension with the constraints from Big Bang Nucleosynthesis. This suggests to relax the exact conservation of the R-parity. The underlying SO(10) Grand Unified Theory together with the bounds from proton decay provide a rationale for considering only bilinear R-parity violating operators. We finally analyze the cosmological implications of this setup by identifying the phenomenologically viable regions of the parameter space.Comment: 28 pages, 5 figures. References added. To appear in JHE

Sources of End Zone Cracking of Pretensioned Concrete Girders

Recent developments of high performance concrete, increasing amounts of prestressing, and increasing use of deep girders have resulted in increasing popularity of precast pretensioned concrete girders in bridge construction. These developments have increasingly contributed to end zone cracking. This paper summarizes the interim results of an ongoing research sponsored by the National Cooperative Highway Research Program (NCHRP) Project 18-14. The objectives of the research are: (1) to establish procedures for the acceptance, repair, or rejection of precast/prestressed concrete girders with longitudinal web cracking, and (2) to prepare a user\u27s manual for the application of these procedures. The results from a national survey of fabricators and users of pretensioned concrete girders and an extensive literature review are presented in this paper

Facing Real-World Challenges of Immunogenicity in Pediatric Inflammatory Bowel Disease

The advent of biological therapies drastically altered the landscape of inflammatory bowel disease (IBD) treatment, making long-term steroid-free remission possible for thousands of patients living with this chronic inflammatory condition that compromises the integrity of the gastrointestinal mucosa. Unfortunately, up to 65% of patients with IBD develop anti-drug antibodies to biologics (1). This is especially problematic for pediatrics, where treatment options are substantially more limited than for adult patients. Currently, only two biologics have approval from the United States (U.S.) Food and Drug Administration (FDA) for pediatric indications in IBD, anti-TNF-α agents infliximab (IFX), and adalimumab (ADM). The fear of losing these two agents to immunogenicity is very real for the providers and the families of the ~70,000 children affected by IBD in the U.S. (2)

Mindful breath awareness meditation facilitates efficiency gains in brain networks: A steady-state visually evoked potentials study

The beneficial effects of mindfulness-based therapeutic interventions have stimulated a rapidly growing body of scientific research into underlying psychological processes. Resulting evidence indicates that engaging with mindfulness meditation is associated with increased performance on a range of cognitive tasks. However, the mechanisms promoting these improvements require further investigation. We studied changes in behavioural performance of 34 participants during a multiple object tracking (MOT) task that taps core cognitive processes, namely sustained selective visual attention and spatial working memory. Concurrently, we recorded the steady-state visually evoked potential (SSVEP), an EEG signal elicited by the continuously flickering moving objects, and indicator of attentional engagement. Participants were tested before and after practicing eight weeks of mindful breath awareness meditation or progressive muscle relaxation as active control condition. The meditation group improved their MOT-performance and exhibited a reduction of SSVEP amplitudes, whereas no such changes were observed in the relaxation group. Neither group changed in self-reported positive affect and mindfulness, while a marginal increase in negative affect was observed in the mindfulness group. This novel way of combining MOT and SSVEP provides the important insight that mindful breath awareness meditation may lead to refinements of attention networks, enabling more efficient use of attentional resources

Planck 2015 results. XIII. Cosmological parameters

We present results based on full-mission Planck observations of temperature and polarization anisotropies of the CMB. These data are consistent with the six-parameter inflationary LCDM cosmology. From the Planck temperature and lensing data, for this cosmology we find a Hubble constant, H0= (67.8 +/- 0.9) km/s/Mpc, a matter density parameter Omega_m = 0.308 +/- 0.012 and a scalar spectral index with n_s = 0.968 +/- 0.006. (We quote 68% errors on measured parameters and 95% limits on other parameters.) Combined with Planck temperature and lensing data, Planck LFI polarization measurements lead to a reionization optical depth of tau = 0.066 +/- 0.016. Combining Planck with other astrophysical data we find N_ eff = 3.15 +/- 0.23 for the effective number of relativistic degrees of freedom and the sum of neutrino masses is constrained to < 0.23 eV. Spatial curvature is found to be |Omega_K| < 0.005. For LCDM we find a limit on the tensor-to-scalar ratio of r <0.11 consistent with the B-mode constraints from an analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP data leads to a tighter constraint of r < 0.09. We find no evidence for isocurvature perturbations or cosmic defects. The equation of state of dark energy is constrained to w = -1.006 +/- 0.045. Standard big bang nucleosynthesis predictions for the Planck LCDM cosmology are in excellent agreement with observations. We investigate annihilating dark matter and deviations from standard recombination, finding no evidence for new physics. The Planck results for base LCDM are in agreement with BAO data and with the JLA SNe sample. However the amplitude of the fluctuations is found to be higher than inferred from rich cluster counts and weak gravitational lensing. Apart from these tensions, the base LCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets