Adaptive genomic structural variation in the grape powdery mildew pathogen, Erysiphe necator.

BackgroundPowdery mildew, caused by the obligate biotrophic fungus Erysiphe necator, is an economically important disease of grapevines worldwide. Large quantities of fungicides are used for its control, accelerating the incidence of fungicide-resistance. Copy number variations (CNVs) are unbalanced changes in the structure of the genome that have been associated with complex traits. In addition to providing the first description of the large and highly repetitive genome of E. necator, this study describes the impact of genomic structural variation on fungicide resistance in Erysiphe necator.ResultsA shotgun approach was applied to sequence and assemble the genome of five E. necator isolates, and RNA-seq and comparative genomics were used to predict and annotate protein-coding genes. Our results show that the E. necator genome is exceptionally large and repetitive and suggest that transposable elements are responsible for genome expansion. Frequent structural variations were found between isolates and included copy number variation in EnCYP51, the target of the commonly used sterol demethylase inhibitor (DMI) fungicides. A panel of 89 additional E. necator isolates collected from diverse vineyard sites was screened for copy number variation in the EnCYP51 gene and for presence/absence of a point mutation (Y136F) known to result in higher fungicide tolerance. We show that an increase in EnCYP51 copy number is significantly more likely to be detected in isolates collected from fungicide-treated vineyards. Increased EnCYP51 copy numbers were detected with the Y136F allele, suggesting that an increase in copy number becomes advantageous only after the fungicide-tolerant allele is acquired. We also show that EnCYP51 copy number influences expression in a gene-dose dependent manner and correlates with fungal growth in the presence of a DMI fungicide.ConclusionsTaken together our results show that CNV can be adaptive in the development of resistance to fungicides by providing increasing quantitative protection in a gene-dosage dependent manner. The results of this work not only demonstrate the effectiveness of using genomics to dissect complex traits in organisms with very limited molecular information, but also may have broader implications for understanding genomic dynamics in response to strong selective pressure in other pathogens with similar genome architectures

Semiclassical interferences and catastrophes in the ionization of Rydberg atoms by half-cycle pulses

A multi-dimensional semiclassical description of excitation of a Rydberg electron by half-cycle pulses is developed and applied to the study of energy- and angle-resolved ionization spectra. Characteristic novel phenomena observable in these spectra such as interference oscillations and semiclassical glory and rainbow scattering are discussed and related to the underlying classical dynamics of the Rydberg electron. Modifications to the predictions of the impulse approximation are examined that arise due to finite pulse durations

Complete quantum teleportation using nuclear magnetic resonance

Quantum mechanics provides spectacular new information processing abilities (Bennett 1995, Preskill 1998). One of the most unexpected is a procedure called quantum teleportation (Bennett et al 1993) that allows the quantum state of a system to be transported from one location to another, without moving through the intervening space. Partial implementations of teleportation (Bouwmeester et al 1997, Boschi et al 1998) over macroscopic distances have been achieved using optical systems, but omit the final stage of the teleportation procedure. Here we report an experimental implementation of the full quantum teleportation operation over inter-atomic distances using liquid state nuclear magnetic resonance (NMR). The inclusion of the final stage enables for the first time a teleportation implementation which may be used as a subroutine in larger quantum computations, or for quantum communication. Our experiment also demonstrates the use of quantum process tomography, a procedure to completely characterize the dynamics of a quantum system. Finally, we demonstrate a controlled exploitation of decoherence as a tool to assist in the performance of an experiment.Comment: 15 pages, 2 figures. Minor differences between this and the published versio

On radiative corrections for unpolarized electron proton elastic scattering

A statistical analysis of the elastic unpolarized electron proton scattering data shows that, at large momentum transfer, the size and the $\epsilon$ dependence of the radiative corrections, as traditionally calculated and applied, may induce large correlations of the parameters of the Rosenbluth fit, which prevent a correct extraction of the electric proton form factor. Using the electron QED structure (radiation) function approach the cross section of elastic electron-proton scattering in leading and next-to leading approximations is calculated and expressed as a correction to the Born cross section, which is different for the electric and the magnetic contribution. When properly applied to the data, it may give the solution to the problem of the discrepancy of the polarized and unpolarized results on electron proton scattering.Comment: 11 pagex, 5 figure

On the complexity of some birational transformations

Using three different approaches, we analyze the complexity of various birational maps constructed from simple operations (inversions) on square matrices of arbitrary size. The first approach consists in the study of the images of lines, and relies mainly on univariate polynomial algebra, the second approach is a singularity analysis, and the third method is more numerical, using integer arithmetics. Each method has its own domain of application, but they give corroborating results, and lead us to a conjecture on the complexity of a class of maps constructed from matrix inversions

Improved quantum circuits for elliptic curve discrete logarithms

We present improved quantum circuits for elliptic curve scalar multiplication, the most costly component in Shor's algorithm to compute discrete logarithms in elliptic curve groups. We optimize low-level components such as reversible integer and modular arithmetic through windowing techniques and more adaptive placement of uncomputing steps, and improve over previous quantum circuits for modular inversion by reformulating the binary Euclidean algorithm. Overall, we obtain an affine Weierstrass point addition circuit that has lower depth and uses fewer $T$ gates than previous circuits. While previous work mostly focuses on minimizing the total number of qubits, we present various trade-offs between different cost metrics including the number of qubits, circuit depth and $T$-gate count. Finally, we provide a full implementation of point addition in the Q# quantum programming language that allows unit tests and automatic quantum resource estimation for all components.Comment: 22 pages, to appear in: Int'l Conf. on Post-Quantum Cryptography (PQCrypto 2020

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab

OBJECTIVE: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach

Validating pore size estimates in a complex microfiber environment on a human MRI system

PURPOSE: Recent advances in diffusion-weighted MRI provide "restricted diffusion signal fraction" and restricting pore size estimates. Materials based on co-electrospun oriented hollow cylinders have been introduced to provide validation for such methods. This study extends this work, exploring accuracy and repeatability using an extended acquisition on a 300 mT/m gradient human MRI scanner, in substrates closely mimicking tissue, that is, non-circular cross-sections, intra-voxel fiber crossing, intra-voxel distributions of pore-sizes, and smaller pore-sizes overall. METHODS: In a single-blind experiment, diffusion-weighted data were collected from a biomimetic phantom on a 3T Connectom system using multiple gradient directions/diffusion times. Repeated scans established short-term and long-term repeatability. The total scan time (54 min) matched similar protocols used in human studies. The number of distinct fiber populations was estimated using spherical deconvolution, and median pore size estimated through the combination of CHARMED and AxCaliber3D framework. Diffusion-based estimates were compared with measurements derived from scanning electron microscopy. RESULTS: The phantom contained substrates with different orientations, fiber configurations, and pore size distributions. Irrespective of one or two populations within the voxel, the pore-size estimates (~5 μm) and orientation-estimates showed excellent agreement with the median values of pore-size derived from scanning electron microscope and phantom configuration. Measurement repeatability depended on substrate complexity, with lower values seen in samples containing crossing-fibers. Sample-level repeatability was found to be good. CONCLUSION: While no phantom mimics tissue completely, this study takes a step closer to validating diffusion microstructure measurements for use in vivo by demonstrating the ability to quantify microgeometry in relatively complex configurations

The Role of Mass and Environment in Multiple Star Formation: A 2MASS Survey of Wide Multiplicity in Three Young Associations

We present the results of a search for wide binary systems among 783 members of three nearby young associations: Taurus-Auriga, Chamaeleon I, and two subgroups of Upper Scorpius. Near-infrared (JHK) imagery from 2MASS was analyzed to search for wide (1-30"; ~150-4500 AU) companions to known association members, using color-magnitude cuts to reject likely background stars. We identify a total of 131 candidate binary companions with colors consistent with physical association, of which 39 have not been identified previously in the literature. Our results suggest that the wide binary frequency is a function of both mass and environment, with significantly higher frequencies among high-mass stars than lower-mass stars and in the T associations than in the OB association. We discuss the implications for wide binary formation and conclude that the environmental dependence is not a direct result of stellar density or total association mass, but instead might depend on another environmental parameter like the gas temperature. We also analyze the mass ratio distribution as a function of mass and find that it agrees with the distribution for field stars to within the statistical uncertainties. The binary populations in these associations generally follow the empirical mass-maximum separation relation observed for field binaries, but we have found one candidate low-mass system (USco-160611.9-193532; Mtot~0.4 Msun) which has a projected separation (10.8"; 1550 AU) much larger than the suggested limit for its mass. (Abridged)Comment: Accepted to ApJ; 27 pages in emulateapj format. The full version of table 2 can be downloaded via http://www.astro.caltech.edu/~alk/tab2.pdf (PDF) or http://www.astro.caltech.edu/~alk/tab2.txt (text