The chloroplast import receptor Toc34 functions as preprotein-regulated GTPase

Toc34 is a protein of the chloroplast outer envelope membrane that acts as receptor for preproteins containing a transit sequence. The recognition of preproteins by Toc34 is regulated by GTP binding and phosphorylation. The phosphorylation site of Toc34 is located at serine 113, close to the postulated triphosphate binding site. This can explain the down-regulation of Toc34 by phosphorylation, resulting in the loss of GTP binding. Vice versa, GTP but not GDP binding of Toc34 influences the phosphorylation. The nucleotide specificity of Toc34 is not only determined by the classical nucleotide binding domains but by a non-typical region at the N-terminus of the protein. As a result, the GTP binding properties are unusual, since the triphosphate moiety of GTP is bound with higher affinity than the purine base. Purified Toc34 hydrolyses GTP at a low rate, which could regulate the receptor function. The rate of hydrolysis is greatly stimulated by a precursor protein

The double well potential in quantum mechanics: a simple, numerically exact formulation

The double well potential is arguably one of the most important potentials in quantum mechanics, because the solution contains the notion of a state as a linear superposition of `classical' states, a concept which has become very important in quantum information theory. It is therefore desirable to have solutions to simple double well potentials that are accessible to the undergraduate student. We describe a method for obtaining the numerically exact eigenenergies and eigenstates for such a model, along with the energies obtained through the Wentzel-Kramers-Brillouin (WKB) approximation. The exact solution is accessible with elementary mathematics, though numerical solutions are required. We also find that the WKB approximation is remarkably accurate, not just for the ground state, but for the excited states as well.Comment: 10 pages, 4 figures; suitable for undergraduate courses in quantum mechanic

Recovering the H II region size statistics from 21-cm tomography

We introduce a novel technique, called ‘granulometry’, to characterize and recover the mean size and the size distribution of H II regions from 21-cm tomography. The technique is easy to implement, but places the previously not very well-defined concept of morphology on a firm mathematical foundation. The size distribution of the cold spots in 21-cm tomography can be used as a direct tracer of the underlying probability distribution of H II region sizes. We explore the capability of the method using large-scale reionization simulations and mock observational data cubes while considering capabilities of Square Kilometre Array 1 (SKA1) low and a future extension to SKA2. We show that the technique allows the recovery of the H II region size distribution with a moderate signal-to-noise ratio from wide-field imaging (SNR 3), for which the statistical uncertainty is sample variance dominated. We address the observational requirements on the angular resolution, the field of view, and the thermal noise limit for a successful measurement. To achieve a full scientific return from 21-cm tomography and to exploit a synergy with 21-cm power spectra, we suggest an observing strategy using wide- field imaging (several tens of square degrees) by an interferometric mosaicking/multibeam observation with additional intermediate baselines (∼2−4 km) in an SKA phase 2

Realistic following behaviors for crowd simulation

International audienceWhile walking through a crowd, a pedestrian experiences a large number of interactions with his neighbors. The nature of these interactions is varied, and it has been observed that macroscopic phenomena emerge from the combination of these local interactions. Crowd models have hitherto considered collision avoidance as the unique type of interactions between individuals, few have considered walking in groups. By contrast, our paper focuses on interactions due to the following behaviors of pedestrians. Following is frequently observed when people walk in corridors or when they queue. Typical macroscopic stop-and-go waves emerge under such traffic conditions. Our contributions are, first, an experimental study on following behaviors, second, a numerical model for simulating such interactions, and third, its calibration, evaluation and applications. Through an experimental approach, we elaborate and calibrate a model from microscopic analysis of real kinematics data collected during experiments. We carefully evaluate our model both at the microscopic and the macroscopic levels. We also demonstrate our approach on applications where following interactions are prominent

Prospects for detecting the 21cm forest from the diffuse intergalactic medium with LOFAR

We discuss the feasibility of the detection of the 21cm forest in the diffuse IGM with the radio telescope LOFAR. The optical depth to the 21cm line has been derived using simulations of reionization which include detailed radiative transfer of ionizing photons. We find that the spectra from reionization models with similar total comoving hydrogen ionizing emissivity but different frequency distribution look remarkably similar. Thus, unless the reionization histories are very different from each other (e.g. a predominance of UV vs. x-ray heating) we do not expect to distinguish them by means of observations of the 21cm forest. Because the presence of a strong x-ray background would make the detection of 21cm line absorption impossible, the lack of absorption could be used as a probe of the presence/intensity of the x-ray background and the thermal history of the universe. Along a random line of sight LOFAR could detect a global suppression of the spectrum from z>12, when the IGM is still mostly neutral and cold, in contrast with the more well-defined, albeit broad, absorption features visible at lower redshift. Sharp, strong absorption features associated with rare, high density pockets of gas could be detected also at z~7 along preferential lines of sight.Comment: 12 pages, 13 figures. MNRAS, in pres

Polymorphism of alpha-1-antitrypsin in hematological malignancies

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

Foregrounds for observations of the cosmological 21 cm line: I. First Westerbork measurements of Galactic emission at 150 MHz in a low latitude field

We present the first results from a series of observations conducted with the Westerbork telescope in the 140--160 MHz range with a 2 arcmin resolution aimed at characterizing the properties of the foregrounds for epoch of reionization experiments. For the first time we have detected fluctuations in the Galactic diffuse emission on scales greater than 13 arcmin at 150 MHz, in the low Galactic latitude area known as Fan region. Those fluctuations have an $rms$ of 14 K. The total intensity power spectrum shows a power--law behaviour down to $\ell \sim 900$ with slope $\beta^I_\ell = -2.2 \pm 0.3$. The detection of diffuse emission at smaller angular scales is limited by residual point sources. We measured an $rms$ confusion noise of $\sim$3 mJy beam$^{-1}$. Diffuse polarized emission was also detected for the first time at this frequency. The polarized signal shows complex structure both spatially and along the line of sight. The polarization power spectrum shows a power--law behaviour down to $\ell \sim 2700$ with slope $\beta^P_\ell = -1.65 \pm 0.15$. The $rms$ of polarization fluctuations is 7.2 K on 4 arcmin scales. By extrapolating the measured spectrum of total intensity emission, we find a contamination on the cosmological signal of $\delta T= \sqrt{\ell (\ell+1) C^I_\ell / 2\pi} \sim 5.7$ K on 5 arcmin scales and a corresponding $rms$ value of $\sim$18.3 K at the same angular scale. The level of the polarization power spectrum is $\delta T \sim 3.3$ K on 5 arcmin scales. Given its exceptionally bright polarized signal, the Fan region is likely to represent an upper limit on the sky brightness at moderate and high Galactic latitude.Comment: Minor corrections made to match the final version printed on A&A. A version with high resolution figures is available at http://www.astro.rug.nl/~bernardi/FAN/fan.pd

Atrial myxoma presenting with orthostatic hypotension in an 84-year-old Hispanic man: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Long-Term Relations Among Prosocial-Media Use, Empathy, and Prosocial Behavior

Despite recent growth of research on the effects of prosocial media, processes underlying these effects are not well understood. Two studies explored theoretically relevant mediators and moderators of the effects of prosocial media on helping. Study 1 examined associations among prosocial- and violent-media use, empathy, and helping in samples from seven countries. Prosocial-media use was positively associated with helping. This effect was mediated by empathy and was similar across cultures. Study 2 explored longitudinal relations among prosocial-video-game use, violent-video-game use, empathy, and helping in a large sample of Singaporean children and adolescents measured three times across 2 years. Path analyses showed significant longitudinal effects of prosocial- and violent-video-game use on prosocial behavior through empathy. Latent-growth-curve modeling for the 2-year period revealed that change in video-game use significantly affected change in helping, and that this relationship was mediated by change in empathy