Transcription activator like effector (TALE)-directed piggyBac transposition in human cells.

Insertional therapies have shown great potential for combating genetic disease and safer methods would undoubtedly broaden the variety of possible illness that can be treated. A major challenge that remains is reducing the risk of insertional mutagenesis due to random insertion by both viral and non-viral vectors. Targetable nucleases are capable of inducing double-stranded breaks to enhance homologous recombination for the introduction of transgenes at specific sequences. However, off-target DNA cleavages at unknown sites can lead to mutations that are difficult to detect. Alternatively, the piggyBac transposase is able perform all of the steps required for integration; therefore, cells confirmed to contain a single copy of a targeted transposon, for which its location is known, are likely to be devoid of aberrant genomic modifications. We aimed to retarget transposon insertions by comparing a series of novel hyperactive piggyBac constructs tethered to a custom transcription activator like effector DNA-binding domain designed to bind the first intron of the human CCR5 gene. Multiple targeting strategies were evaluated using combinations of both plasmid-DNA and transposase-protein relocalization to the target sequence. We demonstrated user-defined directed transposition to the CCR5 genomic safe harbor and isolated single-copy clones harboring targeted integrations

Detection of an atmosphere around the super-Earth 55 Cancri e

We report the analysis of two new spectroscopic observations of the super-Earth 55 Cancri e, in the near infrared, obtained with the WFC3 camera onboard the HST. 55 Cancri e orbits so close to its parent star, that temperatures much higher than 2000 K are expected on its surface. Given the brightness of 55 Cancri, the observations were obtained in scanning mode, adopting a very long scanning length and a very high scanning speed. We use our specialized pipeline to take into account systematics introduced by these observational parameters when coupled with the geometrical distortions of the instrument. We measure the transit depth per wavelength channel with an average relative uncertainty of 22 ppm per visit and find modulations that depart from a straight line model with a 6$\sigma$ confidence level. These results suggest that 55 Cancri e is surrounded by an atmosphere, which is probably hydrogen-rich. Our fully Bayesian spectral retrieval code, T-REx, has identified HCN to be the most likely molecular candidate able to explain the features at 1.42 and 1.54 $\mu$m. While additional spectroscopic observations in a broader wavelength range in the infrared will be needed to confirm the HCN detection, we discuss here the implications of such result. Our chemical model, developed with combustion specialists, indicates that relatively high mixing ratios of HCN may be caused by a high C/O ratio. This result suggests this super-Earth is a carbon-rich environment even more exotic than previously thought.Comment: 10 pages, 10 figures, 4 tables, Accepted for publication in Ap

A population study of gaseous exoplanets

We present here the analysis of 30 gaseous extrasolar planets, with temperatures between 600 and 2400 K and radii between 0.35 and 1.9 $R_\mathrm{Jup}$. The quality of the HST/WFC3 spatially scanned data combined with our specialized analysis tools allow us to study the largest and most self-consistent sample of exoplanetary transmission spectra to date and examine the collective behavior of warm and hot gaseous planets rather than isolated case-studies. We define a new metric, the Atmospheric Detectability Index (ADI) to evaluate the statistical significance of an atmospheric detection and find statistically significant atmospheres around 16 planets out of the 30 analysed. For most of the Jupiters in our sample, we find the detectability of their atmospheres to be dependent on the planetary radius but not on the planetary mass. This indicates that planetary gravity plays a secondary role in the state of gaseous planetary atmospheres. We detect the presence of water vapour in all of the statistically detectable atmospheres, and we cannot rule out its presence in the atmospheres of the others. In addition, TiO and/or VO signatures are detected with 4$\sigma$ confidence in WASP-76 b, and they are most likely present in WASP-121 b. We find no correlation between expected signal-to-noise and atmospheric detectability for most targets. This has important implications for future large-scale surveys.Comment: 14 pages, 12 figures, 3 tables, published in A

Renormalizable acausal theories of classical gravity coupled with interacting quantum fields

We prove the renormalizability of various theories of classical gravity coupled with interacting quantum fields. The models contain vertices with dimensionality greater than four, a finite number of matter operators and a finite or reduced number of independent couplings. An interesting class of models is obtained from ordinary power-counting renormalizable theories, letting the couplings depend on the scalar curvature R of spacetime. The divergences are removed without introducing higher-derivative kinetic terms in the gravitational sector. The metric tensor has a non-trivial running, even if it is not quantized. The results are proved applying a certain map that converts classical instabilities, due to higher derivatives, into classical violations of causality, whose effects become observable at sufficiently high energies. We study acausal Einstein-Yang-Mills theory with an R-dependent gauge coupling in detail. We derive all-order formulas for the beta functions of the dimensionality-six gravitational vertices induced by renormalization. Such beta functions are related to the trace-anomaly coefficients of the matter subsector.Comment: 36 pages; v2: CQG proof-corrected versio

Inequalities for trace anomalies, length of the RG flow, distance between the fixed points and irreversibility

I discuss several issues about the irreversibility of the RG flow and the trace anomalies c, a and a'. First I argue that in quantum field theory: i) the scheme-invariant area Delta(a') of the graph of the effective beta function between the fixed points defines the length of the RG flow; ii) the minimum of Delta(a') in the space of flows connecting the same UV and IR fixed points defines the (oriented) distance between the fixed points; iii) in even dimensions, the distance between the fixed points is equal to Delta(a)=a_UV-a_IR. In even dimensions, these statements imply the inequalities 0 =< Delta(a)=< Delta(a') and therefore the irreversibility of the RG flow. Another consequence is the inequality a =< c for free scalars and fermions (but not vectors), which can be checked explicitly. Secondly, I elaborate a more general axiomatic set-up where irreversibility is defined as the statement that there exist no pairs of non-trivial flows connecting interchanged UV and IR fixed points. The axioms, based on the notions of length of the flow, oriented distance between the fixed points and certain "oriented-triangle inequalities", imply the irreversibility of the RG flow without a global a function. I conjecture that the RG flow is irreversible also in odd dimensions (without a global a function). In support of this, I check the axioms of irreversibility in a class of d=3 theories where the RG flow is integrable at each order of the large N expansion.Comment: 24 pages, 3 figures; expanded intro, improved presentation, references added - CQ

Diazoxide maintains human myocyte volume homeostasis during stress

BACKGROUND: Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition results in significant animal myocyte swelling (6% to10%) and subsequent reduced contractility (10% to 20%). Both are eliminated by the adenosine triphosphate-sensitive potassium channel opener diazoxide (DZX). The relationship between swelling and reduced contractility suggests that the structural change may represent one mechanism of postoperative myocardial stunning. This study evaluated human myocyte volume during stress to investigate if similar phenomena exist in human myocytes. METHODS AND RESULTS: Human atrial myocytes isolated from tissue obtained during cardiac surgery were perfused with Tyrode's physiological solution (20 minutes, 37°C), test solution (20 minutes), and Tyrode's (37°C, 20 minutes). Test solutions (n=6 to 12 myocytes each) included Tyrode's (37°C or 9°C), Tyrode's+DZX (9°C), hyperkalemic cardioplegia (9°C)±DZX, cardioplegia+DZX+HMR 1098 (sarcolemmal adenosine triphosphate-sensitive potassium channel inhibitor, 9°C), cardioplegia+DZX+5-hydroxydeconoate (mitochondrial adenosine triphosphate-sensitive potassium channel inhibitor, 9°C), mild hyposmotic solution±DZX, metabolic inhibition±DZX, and metabolic inhibition+DZX+5-hydroxydeconoate. Myocyte volume was recorded every 5 minutes. Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition resulted in significant human myocyte swelling (8%, 7%, and 6%, respectively; all P<0.05 vs control). In all groups, the swelling was eliminated or lessened by DZX. The addition of channel inhibitors did not significantly alter results. CONCLUSIONS: DZX maintains human myocyte volume homeostasis during stress via an unknown mechanism. DZX may prove to be clinically useful following the elucidation of its specific mechanism of action. (J Am Heart Assoc. 2012;1:jah3-e000778 doi: 10.1161/JAHA.112.000778.

Application of Vis/Nir spectroscopy to establish peach ripening as affected by rootstock

The objective of this paper was to monitor peach ripeness of “Chimarrita” and “Maciel” cultivars, grafted on different rootstocks, using the pulp firmness parameter, as an indicator of harvest time through equipment based on Vis/Nir spectroscopy. The orchard was installed in 2005, has a "V" conduction system with spacing of 5.0 x 1.5 m, and the cultivars are grafted on seven rootstocks: “Capdeboscq”, “Flordaguard”, “Nemaguard”, “Okinawa”, “Tsukuba”, “Umezeiro” and “Viamão”. After harvesting, the fruits were evaluated by the NIR CASE spectrophotometer, establishing categories of pulp firmness, between 40N and 60N for fruits consumed in a long term and <40N for immediate consumption. The analyzed rootstocks alter the peach ripeness of the “Chimarrita” and “Maciel” cultivars. The “Umezeiro” rootstock anticipates harvest for the “Chimarrita” cultivar. The “Nemaguard”/ “Maciel” combination provides fruits with a superior harvest period than the other ones evaluated. The Vis/Nir Spectroscopy is a useful tool to monitor the harvest of “Chimarrita” and “Maciel” cultivars

A General Field-Covariant Formulation Of Quantum Field Theory

In all nontrivial cases renormalization, as it is usually formulated, is not a change of integration variables in the functional integral, plus parameter redefinitions, but a set of replacements, of actions and/or field variables and parameters. Because of this, we cannot write simple identities relating bare and renormalized generating functionals, or generating functionals before and after nonlinear changes of field variables. In this paper we investigate this issue and work out a general field-covariant approach to quantum field theory, which allows us to treat all perturbative changes of field variables, including the relation between bare and renormalized fields, as true changes of variables in the functional integral, under which the functionals Z and W = ln Z behave as scalars. We investigate the relation between composite fields and changes of field variables, and show that, if J are the sources coupled to the elementary fields, all changes of field variables can be expressed as J-dependent redefinitions of the sources L coupled to the composite fields. We also work out the relation between the renormalization of variable-changes and the renormalization of composite fields. Using our transformation rules it is possible to derive the renormalization of a theory in a new variable frame from the renormalization in the old variable frame, without having to calculate it anew. We define several approaches, useful for different purposes, in particular a linear approach where all variable changes are described as linear source redefinitions. We include a number of explicit examples.Comment: 36 pages, 2 figures; v2: minor changes and proof corrections, EPJ