Asynchronous Variational Integrators

We describe a new class of asynchronous variational integrators (AVI) for nonlinear elastodynamics. The AVIs are distinguished by the following attributes: (i) The algorithms permit the selection of independent time steps in each element, and the local time steps need not bear an integral relation to each other; (ii) the algorithms derive from a spacetime form of a discrete version of Hamilton’s variational principle. As a consequence of this variational structure, the algorithms conserve local momenta and a local discrete multisymplectic structure exactly. To guide the development of the discretizations, a spacetime multisymplectic formulation of elastodynamics is presented. The variational principle used incorporates both configuration and spacetime reference variations. This allows a unified treatment of all the conservation properties of the system.A discrete version of reference configuration is also considered, providing a natural definition of a discrete energy. The possibilities for discrete energy conservation are evaluated. Numerical tests reveal that, even when local energy balance is not enforced exactly, the global and local energy behavior of the AVIs is quite remarkable, a property which can probably be traced to the symplectic nature of the algorith

Potent CRISPR-Cas9 inhibitors from Staphylococcus genomes.

Anti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibiting Staphylococcus aureus Cas9 (SauCas9), an alternative to the most commonly used genome editing protein Streptococcus pyogenes Cas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14, and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for DNA cleavage inhibition and have divergent C termini that are required in each case for inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13-AcrIIA15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13-AcrIIA15 as unique bifunctional inhibitors of SauCas9

Perioperative Antibiotic Prophylaxis of Wound and Foreign Body Infections: Microbial Factors Affecting Efficacy

Numerous microbial factors are responsible for perioperative infections and influence the efficacy of antibiotic prophylaxis. These factors include the staphylococcal carrier state, bacterial adherence to a number of host proteins, the production of glycocalyx by sessile bacteria, and shifts in antibiotic resistance. A full understanding of the mechanisms involved will lead to further reductions in the number of postoperative infections. Unfortunately, the microbial factors affecting prophylaxis cannot be evaluated separately under clinical conditions; they are easier to study under circumstances whose bacteriologic features are well defined and in which the presence of foreign materials (e.g., sutures) greatly potentiates pathogenic mechanisms. Such circumstances exist, for example, in infections developing after "clean” surgery and in experimental models. Since even clean wounds are found to be contaminated when sampled carefully, the control of infection is more a quantitative than a qualitative problem. The critical period for the development of infection is short: an antibiotic course not exceeding 24 hours seems effective in preventing infectio

Stability of Actinolite on Venus

Venus currently has a hostile surface environment with temperatures of ~460 C, pres-sures near 92 bars, and an atmosphere composed of super critical CO2 hosting a myriad of other potentially reactive gases (e.g., SO2, HCl, HF). However, it has been proposed that its surface may not have always been so harsh. Models suggest there may have been billions of years of clement conditions allowing an Earth-like environment with liquid water oceans. If such conditions existed, it is possible Venus formed a similar array of hydrous or aqueous minerals as seen on other planets with liquid surface water (e.g., Mars, Earth). Based on thermodynamic modeling, many of these phases would not be stable under the current atmospheric conditions on Venus, dehydrating due to the high temperatures and low concentration of H2O in the atmosphere. However, the rate of decomposition of these phases may allow them to remain present on the surface over geologic time. For example, experiments on the reaction rate of tremolite (Ca2Mg5Si8O22(OH)2) show a 50% decomposition time of 2.7 Gyr for micrometer sized grains in unreactive atmospheres (i.e., without SO2) at 740 K, and a 50% decomposition time of 70 Gyr for crystals several millimeters to centimeters in size. If hydrous minerals can remain on the surface of Venus over geologic time, it has implications for our detection of evidence of these past environments, and also for the overall water budget of the planet. If after surficial dehydration the planet was able to still store water in its crust, possible processes such as subduction or metamorphism could still have operated using stored water long after liquid surface water evaporated. Several previous studies have focused on experimental investigations of mineral stability on Venus. In particular, the works of studied the decomposition rate of tremolite under conditions relevant to Venus. As their focus was on decomposition of the mineral due to lack of water in the atmosphere, their experiments were undertaken using only CO2 or N2 gas at atmospheric pressure. Re-cent experiments have examined reactivity of other minerals with the Venusian atmosphere using more complex gas compositions at similar pressures to those seen on Venus. These studies show reaction of silicate minerals with atmospheric components on relatively short timescales (i.e., on the order of days). The reported reactions of silicate materials in both studies produced iron oxides, Ca sulfates, and Na sulfates. These ions are present in many amphiboles, and Ca was proposed by Johnson and Fegley to potentially have an important role in the decomposition mechanism for tremolite, with the Ca-O bond being the first to break during decomposition. The potential involvement of Ca in both processes raises the question of whether or not the reaction to form a secondary mineral phase will influence the rate of amphibole break-down (e.g., discussion in for tremolite). Additionally, reaction of Ca with atmospheric gases may result in a different secondary mineral assemblage than simple amphibole decomposition, which will need to be recognized when searching for evidence of past hydrated minerals on the Venusian surface. In order to understand the effect of this reaction on the overall preservation potential of amphibole on the surface of Venus, we are conducting experiments in both reactive and nonreactive atmospheres using the mineral actinolite (Ca2(Mg,Fe)5Si8O22(OH)2), an amphibole with similar crystal structure to tremolite that contains both Ca and Fe

Spatial mapping of band bending in semiconductor devices using in-situ quantum sensors

Band bending is a central concept in solid-state physics that arises from local variations in charge distribution especially near semiconductor interfaces and surfaces. Its precision measurement is vital in a variety of contexts from the optimisation of field effect transistors to the engineering of qubit devices with enhanced stability and coherence. Existing methods are surface sensitive and are unable to probe band bending at depth from surface or bulk charges related to crystal defects. Here we propose an in-situ method for probing band bending in a semiconductor device by imaging an array of atomic-sized quantum sensing defects to report on the local electric field. We implement the concept using the nitrogen-vacancy centre in diamond, and map the electric field at different depths under various surface terminations. We then fabricate a two-terminal device based on the conductive two-dimensional hole gas formed at a hydrogen-terminated diamond surface, and observe an unexpected spatial modulation of the electric field attributed to a complex interplay between charge injection and photo-ionisation effects. Our method opens the way to three-dimensional mapping of band bending in diamond and other semiconductors hosting suitable quantum sensors, combined with simultaneous imaging of charge transport in complex operating devices.Comment: This is a pre-print of an article published in Nature Electronics. The final authenticated version is available online at https://dx.doi.org/10.1038/s41928-018-0130-

Preheating and Affleck-Dine leptogenesis after thermal inflation

Previously, we proposed a model of low energy Affleck-Dine leptogenesis in the context of thermal inflation. The lepton asymmetry is generated at the end of thermal inflation, which occurs at a relatively low energy scale with the Hubble parameter somewhere in the range 1 \keV \lesssim H \lesssim 1 \MeV. Thus Hubble damping will be ineffective in bringing the Affleck-Dine field into the lepton conserving region near the origin, leaving the possibility that the lepton number could be washed out. Previously, we suggested that preheating could damp the amplitude of the Affleck-Dine field allowing conservation of the lepton number. In this paper, we demonstrate numerically that preheating does efficiently damp the amplitude of the Affleck-Dine field and that the lepton number is conserved as the result. In addition to demonstrating a crucial aspect of our model, it also opens the more general possibility of low energy Affleck-Dine baryogenesis.Comment: 38 pages, 17 figure

Staphylococcal Small Colony Variants Have Novel Mechanisms for Antibiotic Resistance

Over the past 4 years, a variant subpopulation of Staphylococcus aureus has been characterized that is defective in electron transport. These organisms grow slowly and are typical of the previously described small colony variants (SCVs). Indeed, many earlier papers included data that are consistent with defective respiratory activity in SCVs. We present a hypothesis that serves as biochemical basis for the development of SCVs. These variants are particularly interesting because they have been associated with very persistent infections, and they are more resistant to many antibiotics than normal S. aureus. Because of their slow growth, atypical colonial morphology, and unusual biochemical profile, they are easily missed or misidentified in the clinical laboratory. This is of some significance, as this subpopulation is more resistant to antibiotics than the parent population from which they arose. When an infection is particularly resistant to therapy, persists for a long period, or fails to respond to apparently adequate antimicrobial therapy, clinicians and clinical laboratory personnel should consider special efforts to search for SCV

Host Factors Selectively Increase Staphylococcal Adherence on Inserted Catheters: A Role for Fibronectin and Fibrinogen or Fibrin

Intravascular catheters are prone to staphylococcal infections. To study the role in staphylococcal adherence played by fibrinogen or fibrin and fibronectin deposited on inserted catheters, 187 peripheral or central cannulae were prospectively removed from hospitalized patients. Compared with uninserted catheters, which allowed only minimal adherence, previously inserted catheters promoted significant adherence of staphylococcal isolates from patients with intravenous device infections. Adhesion-promoting properties were studied with laboratory strains having well-defined affinities for either fibronectin or fibrinogen adherence of Staphylococcus aureus Cowan I, which has the highest affinity for both adhesins, was more strongly promoted (10- to 50-fold) on inserted cannulae than was that of S. aureus Wood 46 (4- to lO-fold) or Staphylococcus epidermidis Rp 12 (2.2-fold), which has no affinity for fibrinogen but does for fibronectin. Although all types of cannulae contained significant amounts of fibrin, which may promote adherence of coagulase-positive staphylococci, results obtained with coagulase-negative isolates suggested that in vivo-deposited fibronectin is also a critical determinant in this proces