On the Calibration of Full-polarization 86GHz Global VLBI Observations

We report the development of a semi-automatic pipeline for the calibration of 86 GHz full-polarization observations performed with the Global Millimeter-VLBI array (GMVA) and describe the calibration strategy followed in the data reduction. Our calibration pipeline involves non-standard procedures, since VLBI polarimetry at frequencies above 43 GHz is not yet well established. We also present, for the first time, a full-polarization global-VLBI image at 86 GHz (source 3C 345), as an example of the final product of our calibration pipeline, and discuss the effect of instrumental limitations on the fidelity of the polarization images. Our calibration strategy is not exclusive for the GMVA, and could be applied on other VLBI arrays at millimeter wavelengths. The use of this pipeline will allow GMVA observers to get fully-calibrated datasets shortly after the data correlation.Comment: 10 pages, 10 figures. Accepted for publication in A&

Precision astrometry of pulsars and other compact radio sources in the globular cluster M15

The globular cluster (GC) M15 (NGC 7078) is host to at least eight pulsars and two low mass X-ray binaries (LMXBs), one of which is also visible in the radio regime. Here we present the results of a multi-epoch global very long baseline interferometry (VLBI) campaign aiming at i) measuring the proper motion of the known compact radio sources; ii) finding and classifying thus far undetected compact radio sources in the GC; and iii) detecting a signature of the putative intermediate mass black hole (IMBH) proposed to reside at the core of M15. We measure the sky motion in right ascension (µa) and declination (µd) of the pulsars M15A and M15C and of the LMXB AC211 to be (µa,µd)M15A = (-0.54 ± 0.14,-4.33 ± 0.25) mas yr-1, (µa,µd)M15C = (-0.75 ± 0.09,-3.52 ± 0.13) mas yr-1, and (µa, µd)AC211 = (-0.46 ± 0.08,-4.31 ± 0.20) mas yr-1, respectively. Based on these measurements we estimate the global proper motion of M15 to be (µa, µd) = (-0.58 ± 0.18,-4.05 ± 0.34) mas yr -1. We detect two previously known but unclassified compact sources within our field of view. Our observations indicate that one them is of extragalactic origin while the other one is a foreground source, quite likely an LMXB. The double neutron star system M15C became fainter during the observations, disappeared for one year and is now observable again-an effect possibly caused by geodetic precession. The LMXB AC211 shows a double lobed structure in one of the observations indicative of an outburst during this campaign. With the inclusion of the last two of a total of seven observations we confirm the upper mass limit for a putative IMBH to be M•< 500 M·. © 2014 ESO

Journaling the Art of Teaching: Multimodal Responding for Narrative Inquiry

Research underscores the integral role that teachers’ recurring narratives play in their everyday teaching agendas. Like the students in their classrooms, teachers comprise a diverse group of individuals representing a myriad of ways to learn and teach, stemming from such factors as pedagogical approaches, prior life experiences, and familial relationships. Applying multimodal learning to response journaling expands teacher candidates’ opportunities to address the role that narratives play in developing their daily repertoires of practice in language arts. Hence, further investigation is needed to expand the range of practices available for fostering teacher narrative inquiry. Methodologically supported by action research in relation to narrative inquiry and multimodal learning, we asked, What are the effects of multimodal journaling on the recurring narratives of teacher candidates in a junior-intermediate language/arts methods class

Targeting the IspD enzyme in the MEP pathway: identification of a novel fragment class

Enzymes of the 2-C-methylerythritol-d-erythritol 4-phosphate 2C-methyl-D-erythritol 4-phosphate (MEP) pathway (MEP pathway or non-mevalonate pathway) are responsible for the synthesis of universal precursors of the huge large and structurally diverse family of isoprenoids. This pathway is absent in humans, but present in many pathogenic organisms and plants, making it an attractive source of drug targets. Here, we present a high-throughput screening approach that led to the discovery of a novel fragment hit active against the third enzyme of the MEP pathway, PfIspD. A systematic SAR investigation afforded a novel chemical structure with a balanced activity-stability profile (16). Using a homology model of PfIspD, we proposed a putative binding mode for our newly identified inhibitors that sets the stage for structure-guided optimization

Single-particle-sensitive imaging of freely propagating ultracold atoms

We present a novel imaging system for ultracold quantum gases in expansion. After release from a confining potential, atoms fall through a sheet of resonant excitation laser light and the emitted fluorescence photons are imaged onto an amplified CCD camera using a high numerical aperture optical system. The imaging system reaches an extraordinary dynamic range, not attainable with conventional absorption imaging. We demonstrate single-atom detection for dilute atomic clouds with high efficiency where at the same time dense Bose-Einstein condensates can be imaged without saturation or distortion. The spatial resolution can reach the sampling limit as given by the 8 \mu m pixel size in object space. Pulsed operation of the detector allows for slice images, a first step toward a 3D tomography of the measured object. The scheme can easily be implemented for any atomic species and all optical components are situated outside the vacuum system. As a first application we perform thermometry on rubidium Bose-Einstein condensates created on an atom chip.Comment: 24 pages, 10 figures. v2: as publishe

Search for the active ingredients from a 2-aminothiazole DMSO stock solution with antimalarial activity

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme Pf IspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against Pf IspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound

Punctuation effects in English and Esperanto texts

A statistical physics study of punctuation effects on sentence lengths is presented for written texts: {\it Alice in wonderland} and {\it Through a looking glass}. The translation of the first text into esperanto is also considered as a test for the role of punctuation in defining a style, and for contrasting natural and artificial, but written, languages. Several log-log plots of the sentence length-rank relationship are presented for the major punctuation marks. Different power laws are observed with characteristic exponents. The exponent can take a value much less than unity ($ca.$ 0.50 or 0.30) depending on how a sentence is defined. The texts are also mapped into time series based on the word frequencies. The quantitative differences between the original and translated texts are very minutes, at the exponent level. It is argued that sentences seem to be more reliable than word distributions in discussing an author style.Comment: 13 pages, 7 figures (3x2+1), 60 reference

Comparative flavonoid profile of orange (Citrus sinensis) flavedo and albedo extracted by conventional and emerging techniques using UPLC-IMS-MS, chemometrics and antioxidant effects

Introduction: Citrus fruits are one of the most frequently counterfeited processed products in the world. In the juice production alone, the peels, divided into flavedo and albedo, are the main waste product. The extracts of this by-product are enriched with many bioactive substances. Newer extraction techniques generally have milder extraction conditions with simultaneous improvement of the extraction process. Methods: This study presents a combinatorial approach utilizing data-independent acquisition-based ion mobility spectrometry coupled to tandem mass spectrometry. Integrating orthogonal collision cross section (CCS) data matching simultaneously improves the confidence in metabolite identification in flavedo and albedo tissues from Citrus sinensis. Furthermore, four different extraction approaches [conventional, ultrasonic, High Hydrostatic Pressure (HHP) and Pulsed Electric Field (PEF)] with various optimized processing conditions were compared in terms of antioxidant effects and flavonoid profile particularly polymethoxy flavones (PMFs). Results: A total number of 57 metabolites were identified, 15 of which were present in both flavedo and albedo, forming a good qualitative overlapping of distributed flavonoids. For flavedo samples, the antioxidant activity was higher for PEF and HHP treated samples compared to other extraction methods. However, ethyl acetate extract exhibited the highest antioxidant effects in albedo samples attributed to different qualitative composition content rather than various quantities of same metabolites. The optimum processing conditions for albedo extraction using HHP and PEF were 200 MPa and 15 kJ/kg at 10 kV, respectively. While, HHP at medium pressure (400 MPa) and PEF at 15 kJ/kg/3 kV were the optimum conditions for flavedo extraction. Conclusion: Chemometric analysis of the dataset indicated that orange flavedo can be a valid source of soluble phenolic compounds especially PMFs. In order to achieve cross-application of production, future study should concentrate on how citrus PMFs correlate with biological engineering techniques such as breeding, genetic engineering, and fermentation engineering

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas

Targeting the IspD Enzyme in the MEP Pathway: Identification of a Novel Fragment Class

The enzymes of the 2-C-methylerythritol-d-erythritol 4-phosphate (MEP) pathway (MEP pathway or non-mevalonate pathway) are responsible for the synthesis of universal precursors of the large and structurally diverse family of isoprenoids. This pathway is absent in humans, but present in many pathogenic organisms and plants, making it an attractive source of drug targets. Here, we present a high-throughput screening approach that led to the discovery of a novel fragment hit active against the third enzyme of the MEP pathway, PfIspD. A systematic SAR investigation afforded a novel chemical structure with a balanced activity–stability profile (16). Using a homology model of PfIspD, we proposed a putative binding mode for our newly identified inhibitors that sets the stage for structure-guided optimization