Evidence for a Proton–Protein Symport Mechanism in the Anthrax Toxin Channel

The toxin produced by Bacillus anthracis, the causative agent of anthrax, is composed of three proteins: a translocase heptameric channel, (PA63)7, formed from protective antigen (PA), which allows the other two proteins, lethal and edema factors (LF and EF), to translocate across a host cell's endosomal membrane, disrupting cellular homeostasis. It has been shown that (PA63)7 incorporated into planar phospholipid bilayer membranes forms a channel capable of transporting LF and EF. Protein translocation through the channel is driven by a proton electrochemical potential gradient on a time scale of seconds. A paradoxical aspect of this is that although LFN (the N-terminal 263 residues of LF), on which most of our experiments were performed, has a net negative charge, it is driven through the channel by a cis-positive voltage. We have explained this by claiming that the (PA63)7 channel strongly disfavors the entry of negatively charged residues on proteins to be translocated, and hence the aspartates and glutamates on LFN enter protonated (i.e., neutralized). Therefore, the translocated species is positively charged. Upon exiting the channel, the protons that were picked up from the cis solution are released into the trans solution, thereby making this a proton–protein symporter. Here, we provide further evidence of such a mechanism by showing that if only one SO3−, which is essentially not titratable, is introduced at most positions in LFN, through the reaction of an introduced cysteine residue at those positions with 2-sulfonato-ethyl-methanethiosulfonate, voltage-driven LFN translocation is drastically inhibited. We also find that a site that disfavors the entry of negatively charged residues into the (PA63)7 channel resides at or near its Φ-clamp, the ring of seven phenylalanines near the channel's entrance

3D integrated superconducting qubits

As the field of superconducting quantum computing advances from the few-qubit stage to larger-scale processors, qubit addressability and extensibility will necessitate the use of 3D integration and packaging. While 3D integration is well-developed for commercial electronics, relatively little work has been performed to determine its compatibility with high-coherence solid-state qubits. Of particular concern, qubit coherence times can be suppressed by the requisite processing steps and close proximity of another chip. In this work, we use a flip-chip process to bond a chip with superconducting flux qubits to another chip containing structures for qubit readout and control. We demonstrate that high qubit coherence ($T_1$, $T_{2,\rm{echo}} > 20\,\mu$s) is maintained in a flip-chip geometry in the presence of galvanic, capacitive, and inductive coupling between the chips

Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson's disease and depression.

Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems

A self-interacting partially directed walk subject to a force

We consider a directed walk model of a homopolymer (in two dimensions) which is self-interacting and can undergo a collapse transition, subject to an applied tensile force. We review and interpret all the results already in the literature concerning the case where this force is in the preferred direction of the walk. We consider the force extension curves at different temperatures as well as the critical-force temperature curve. We demonstrate that this model can be analysed rigorously for all key quantities of interest even when there may not be explicit expressions for these quantities available. We show which of the techniques available can be extended to the full model, where the force has components in the preferred direction and the direction perpendicular to this. Whilst the solution of the generating function is available, its analysis is far more complicated and not all the rigorous techniques are available. However, many results can be extracted including the location of the critical point which gives the general critical-force temperature curve. Lastly, we generalise the model to a three-dimensional analogue and show that several key properties can be analysed if the force is restricted to the plane of preferred directions.Comment: 35 pages, 14 figure

A Weighted Estimate for the Square Function on the Unit Ball in \C^n

We show that the Lusin area integral or the square function on the unit ball of \C^n, regarded as an operator in weighted space $L^2(w)$ has a linear bound in terms of the invariant $A_2$ characteristic of the weight. We show a dimension-free estimate for the ``area-integral'' associated to the weighted $L^2(w)$ norm of the square function. We prove the equivalence of the classical and the invariant $A_2$ classes.Comment: 11 pages, to appear in Arkiv for Matemati

Dissociative recombination measurements of HCl+ using an ion storage ring

We have measured dissociative recombination of HCl+ with electrons using a merged beams configuration at the heavy-ion storage ring TSR located at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. We present the measured absolute merged beams recombination rate coefficient for collision energies from 0 to 4.5 eV. We have also developed a new method for deriving the cross section from the measurements. Our approach does not suffer from approximations made by previously used methods. The cross section was transformed to a plasma rate coefficient for the electron temperature range from T=10 to 5000 K. We show that the previously used HCl+ DR data underestimate the plasma rate coefficient by a factor of 1.5 at T=10 K and overestimate it by a factor of 3.0 at T=300 K. We also find that the new data may partly explain existing discrepancies between observed abundances of chlorine-bearing molecules and their astrochemical models.Comment: Accepted for publication in ApJ (July 7, 2013

Boundaries of Siegel Disks: Numerical Studies of their Dynamics and Regularity

Siegel disks are domains around fixed points of holomorphic maps in which the maps are locally linearizable (i.e., become a rotation under an appropriate change of coordinates which is analytic in a neighborhood of the origin). The dynamical behavior of the iterates of the map on the boundary of the Siegel disk exhibits strong scaling properties which have been intensively studied in the physical and mathematical literature. In the cases we study, the boundary of the Siegel disk is a Jordan curve containing a critical point of the map (we consider critical maps of different orders), and there exists a natural parametrization which transforms the dynamics on the boundary into a rotation. We compute numerically this parameterization and use methods of harmonic analysis to compute the global Holder regularity of the parametrization for different maps and rotation numbers. We obtain that the regularity of the boundaries and the scaling exponents are universal numbers in the sense of renormalization theory (i.e., they do not depend on the map when the map ranges in an open set), and only depend on the order of the critical point of the map in the boundary of the Siegel disk and the tail of the continued function expansion of the rotation number. We also discuss some possible relations between the regularity of the parametrization of the boundaries and the corresponding scaling exponents. (C) 2008 American Institute of Physics.NSFMathematic

Electronic Raman scattering in YBCO and other superconducting cuprates

Superconductivity induced structures in the electronic Raman spectra of high-Tc superconductors are computed using the results of ab initio LDA-LMTO three-dimensional band structure calculations via numerical integrations of the mass fluctuations, either in the whole 3D Brillouin zone or limiting the integrations to the Fermi surface. The results of both calculations are rather similar, the Brillouin zone integration yielding additional weak structures related to the extended van Hove singularities. Similar calculations have been performed for the normal state of these high-Tc cuprates. Polarization configurations have been investigated and the results have been compared to experimental spectra. The assumption of a simple d_(x^2-y^2)-like gap function allows us to explain a number of experimental features but is hard to reconcile with the relative positions of the A1g and B1g peaks.Comment: 14 pages, LaTeX (RevTeX), 5 PostScript figures, uses multicol.sty, submitted to PR

Twin paradox and space topology

If space is compact, then a traveller twin can leave Earth, travel back home without changing direction and find her sedentary twin older than herself. We show that the asymmetry between their spacetime trajectories lies in a topological invariant of their spatial geodesics, namely the homotopy class. This illustrates how the spacetime symmetry invariance group, although valid {\it locally}, is broken down {\it globally} as soon as some points of space are identified. As a consequence, any non--trivial space topology defines preferred inertial frames along which the proper time is longer than along any other one.Comment: 6 pages, latex, 3 figure

Energy-sensitive imaging detector applied to the dissociative recombination of D2H+

We report on an energy-sensitive imaging detector for studying the fragmentation of polyatomic molecules in the dissociative recombination of fast molecular ions with electrons. The system is based on a large area (10 cm x 10 cm) position-sensitive, double-sided Si-strip detector with 128 horizontal and 128 vertical strips, whose pulse height information is read out individually. The setup allows to uniquely identify fragment masses and is thus capable of measuring branching ratios between different fragmentation channels, kinetic energy releases, as well as breakup geometries, as a function of the relative ion-electron energy. The properties of the detection system, which has been installed at the TSR storage ring facility of the Max-Planck Institute for Nuclear Physics in Heidelberg, is illustrated by an investigation of the dissociative recombination of the deuterated triatomic hydrogen cation D2H+. A huge isotope effect is observed when comparing the relative branching ratio between the D2+H and the HD+D channel; the ratio 2B(D2+H)/B(HD+D), which is measured to be 1.27 +/- 0.05 at relative electron-ion energies around 0 eV, is found to increase to 3.7 +/- 0.5 at ~5 eV.Comment: 11 pages, 12 figures, submitted to Physical Review