The Multi-Configurational Hartree-Fock close-coupling ansatz: application to Argon photoionization cross section and delays

We present a robust, ab initio method for addressing atom-light interactions and apply it to photoionization of argon. We use a close-coupling ansatz constructed on a multi-configurational Hartree-Fock description of localized states and B-spline expansions of the electron radial wave functions. In this implementation, the general many-electron problem can be tackled thanks to the use of the ATSP2K libraries [CPC 176 (2007) 559]. In the present contribution, we combine this method with exterior complex scaling, thereby allowing for the computation of the complex partial amplitudes that encode the whole dynamics of the photoionization process. The method is validated on the 3s3p6np series of resonances converging to the 3s extraction. Then, it is used for computing the energy dependent differential atomic delay between 3p and 3s photoemission, and agreement is found with the measurements of Gu\'enot et al. [PRA 85 (2012) 053424]. The effect of the presence of resonances in the one-photon spectrum on photoionization delay measurements is studied.Comment: 15 pages, 8 figures, 4 table

Syntax for free: representing syntax with binding using parametricity

We show that, in a parametric model of polymorphism, the type ∀ α. ((α → α) → α) → (α → α → α) → α is isomorphic to closed de Bruijn terms. That is, the type of closed higher-order abstract syntax terms is isomorphic to a concrete representation. To demonstrate the proof we have constructed a model of parametric polymorphism inside the Coq proof assistant. The proof of the theorem requires parametricity over Kripke relations. We also investigate some variants of this representation

A theoretical study of the C- 4So_3/2 and 2Do_{3/2,5/2} bound states and C ground configuration: fine and hyperfine structures, isotope shifts and transition probabilities

This work is an ab initio study of the 2p3 4So_3/2, and 2Do_{3/2,5/2} states of C- and 2p2 3P_{0,1,2}, 1D_2, and 1S_0 states of neutral carbon. We use the multi-configuration Hartree-Fock approach, focusing on the accuracy of the wave function itself. We obtain all C- detachment thresholds, including correlation effects to about 0.5%. Isotope shifts and hyperfine structures are calculated. The achieved accuracy of the latter is of the order of 0.1 MHz. Intra-configuration transition probabilities are also estimated.Comment: 15 pages, 2 figures, 12 table

Automatically proving equivalence by type-safe reflection

We are also grateful for the support of the Scottish Informatics and Computer Science Alliance (SICSA) and EPSRC grant EP/N024222/1.One difficulty with reasoning and programming with dependent types is that proof obligations arise naturally once programs become even moderately sized. For example, implementing an adder for binary numbers indexed over their natural number equivalents naturally leads to proof obligations for equalities of expressions over natural numbers. The need for these equality proofs comes, in intensional type theories, from the fact that the propositional equality enables us to prove as equal terms that are not judgementally equal, which means that the typechecker can’t always obtain equalities by reduction. As far as possible, we would like to solve such proof obligations automatically. In this paper, we show one way to automate these proofs by reflection in the dependently typed programming language Idris. We show how defining reflected terms indexed by the original Idris expression allows us to construct and manipulate proofs. We build a hierarchy of tactics for proving equivalences in semi-groups, monoids, commutative monoids, groups, commutative groups, semi-rings and rings. We also show how each tactic reuses those from simpler structures, thus avoiding duplication of code and proofs.Postprin

GluA4-Targeted AAV Vectors Deliver Genes Selectively to Interneurons while Relying on the AAV Receptor for Entry

Selective gene delivery into subtypes of interneurons remains an important challenge in vector development. Adeno-associated virus (AAV) vector particles are especially promising for intracerebral injections. For cell entry, AAV2 particles are supposed to attach to heparan-sulfate proteoglycans (HSPGs) followed by endocytosis via the AAV receptor (AAVR). Here, we assessed engineered AAV particles deficient in HSPG attachment but competent in recognizing the glutamate receptor 4 (GluA4, also known as GluRD or GRIA4) through a displayed GluA4-specific DARPin (designed ankyrin repeat protein). When injected into the mouse brain, histological evaluation revealed that in various regions, more than 90% of the transduced cells were interneurons, mainly of the parvalbumin-positive subtype. Although part of the selectivity was mediated by the DARPin, the chosen spleen focus-forming virus (SFFV) promoter had contributed as well. Further analysis revealed that the DARPin mediated selective attachment to GluA4-positive cells, whereas gene delivery required expression of AAVR. Our data suggest that cell selectivity of AAV particles can be modified rationally and efficiently through DARPins, but expression of the AAV entry receptor remains essential

Imaging of Hereditary Hemorrhagic Telangiectasia

This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients

Interpreting Attoclock Measurements of Tunnelling Times

Resolving in time the dynamics of light absorption by atoms and molecules, and the electronic rearrangement this induces, is among the most challenging goals of attosecond spectroscopy. The attoclock is an elegant approach to this problem, which encodes ionization times in the strong-field regime. However, the accurate reconstruction of these times from experimental data presents a formidable theoretical challenge. Here, we solve this problem by combining analytical theory with ab-initio numerical simulations. We apply our theory to numerical attoclock experiments on the hydrogen atom to extract ionization time delays and analyse their nature. Strong field ionization is often viewed as optical tunnelling through the barrier created by the field and the core potential. We show that, in the hydrogen atom, optical tunnelling is instantaneous. By calibrating the attoclock using the hydrogen atom, our method opens the way to identify possible delays associated with multielectron dynamics during strong-field ionization.Comment: 33 pages, 10 figures, 3 appendixe

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody

Background: The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product. Methodology/Principal Findings: To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV) RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue) of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER). Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO) cell-produced 2G12. Conclusions: Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for biopharmaceutical development and production