MESMER: MeerKAT Search for Molecules in the Epoch of Reionization

[Abridged] Observations of molecular gas at all redshifts are critical for measuring the cosmic evolution in molecular gas density and understanding the star-formation history of the Universe. The 12CO molecule (J=1-0 transition = 115.27 GHz) is the best proxy for extragalactic H2, which is the gas reservoir from which star formation occurs, and has been detected out to z~6. Typically, redshifted high-J lines are observed at mm-wavelengths, the most commonly targeted systems exhibiting high SFRs (e.g. submm galaxies), and far-IR-bright QSOs. While the most luminous objects are the most readily observed, detections of more typical galaxies with modest SFRs are essential for completing the picture. ALMA will be revolutionary in terms of increasing the detection rate and pushing the sensitivity limit down to include such galaxies, however the limited FoV when observing at such high frequencies makes it difficult to use ALMA for studies of the large-scale structure traced out by molecular gas in galaxies. This article introduces a strategy for a systematic search for molecular gas during the EoR (z~7 and above), capitalizing on the fact that the J=1-0 transition of 12CO enters the upper bands of cm-wave instruments at high-z. The FoV advantage gained by observing at such frequencies, coupled with modern broadband correlators allows significant cosmological volumes to be probed on reasonable timescales. In this article we present an overview of our future observing programme which has been awarded 6,500 hours as one of the Large Survey Projects for MeerKAT, the forthcoming South African SKA pathfinder instrument. Its large FoV and correlator bandwidth, and high-sensitivity provide unprecedented survey speed for such work. An existing astrophysical simulation is coupled with instrumental considerations to demonstrate the feasibility of such observations and predict detection rates.Comment: 7 pages, 4 figures, to appear in the proceedings of "Astronomy with megastructures: Joint science with the E-ELT and SKA", 10-14 May 2010, Crete, Greece (Eds: Isobel Hook, Dimitra Rigopoulou, Steve Rawlings and Aris Karastergiou

Epidermal Growth Factor–PEG Functionalized PAMAM-Pentaethylenehexamine Dendron for Targeted Gene Delivery Produced by Click Chemistry

Aim of this study was the site-specific conjugation of an epidermal growth factor (EGF)-polyethylene glycol (PEG) chain by click chemistry onto a poly(amido amine) (PAMAM) dendron, as a key step toward defined multifunctional carriers for targeted gene delivery. For this purpose, at first propargyl amine cored PAMAM dendrons with ester ends were synthesized. The chain terminal ester groups were then modified by oligoamines with different secondary amino densities. The oligoamine-modified PAMAM dendrons were well biocompatible, as demonstrated in cytotoxicity assays. Among the different oligoamine-modified dendrons, PAMAM-pentaethylenehexamine (PEHA) dendron polyplexes displayed the best gene transfer ability. Conjugation of PAMAM-PEHA dendron with PEG spacer was conducted via click reaction, which was performed before amidation with PEHA. The resultant PEG-PAMAM-PEHA copolymer was then coupled with EGF ligand. pDNA transfections in HuH-7 hepatocellular carcinoma cells showed a 10-fold higher efficiency with the polyplexes containing conjugated EGF as compared to the ligand-free ones, demonstrating the concept of ligand targeting. Overall gene transfer efficiencies, however, were moderate, suggesting that additional measures for overcoming subsequent intracellular bottlenecks in delivery have to be taken

Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin

Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS2a). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS2a fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg−1 AlPcS2a, and 6 h after direct intratumour injection of 50 μg gelonin (PCI) or a similar volume of phosphate-buffered saline (PDT controls), tumour-bearing animals were exposed to red light (150 J cm−2). Complete response was observed for more than 100 days in 50% of the PCI tumours but only 10% of the PDT tumours (P<0.01). In tumours examined histologically 4 days after light delivery, the depth of necrosis was 3–4 mm after PDT, but 7 mm after PCI. The deeper effect after PCI demonstrates that the light fluence needed to kill tumour is less than with PDT. We conclude that PCI with gelonin can markedly enhance the effect of PDT on this type of tumour and may have a role clinically as an adjunct to surgery to control localised disease

Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder

Extending cosmological tests of General Relativity with the Square Kilometre Array

Tests of general relativity (GR) are still in their infancy on cosmological scales, but forthcoming experiments promise to greatly improve their precision over a wide range of distance scales and redshifts. One such experiment, the Square Kilometre Array (SKA), will carry out several wide and deep surveys of resolved and unresolved neutral hydrogen (H i) 21 cm line-emitting galaxies, mapping a significant fraction of the sky from $0\leqslant z\lesssim 6$. I present forecasts for the ability of a suite of possible SKA H i surveys to detect deviations from GR by reconstructing the cosmic expansion and growth history. SKA Phase 1 intensity mapping surveys can achieve sub-1% measurements of $f{\sigma }_{8}$ out to $z\approx 1$, with an SKA1-MID Band 2 survey out to z lesssim 0.6 able to surpass contemporary spectroscopic galaxy surveys such as DESI and Euclid in terms of constraints on modified gravity parameters if challenges such as foreground contamination can be tackled effectively. A more futuristic Phase 2 H i survey of $\sim {10}^{9}$ spectroscopic galaxy redshifts would be capable of detecting a $\sim 2\%$ modification of the Poisson equation out to z ≈ 2

SciPy 1.0: fundamental algorithms for scientific computing in Python.

SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments