Identification and characterization of the dif Site from Bacillus subtilis

Bacteria with circular chromosomes have evolved systems that ensure multimeric chromosomes, formed by homologous recombination between sister chromosomes during DNA replication, are resolved to monomers prior to cell division. The chromosome dimer resolution process in Escherichia coli is mediated by two tyrosine family site-specific recombinases, XerC and XerD, and requires septal localization of the division protein FtsK. The Xer recombinases act near the terminus of chromosome replication at a site known as dif (Ecdif). In Bacillus subtilis the RipX and CodV site-specific recombinases have been implicated in an analogous reaction. We present here genetic and biochemical evidence that a 28-bp sequence of DNA (Bsdif), lying 6° counterclockwise from the B. subtilis terminus of replication (172°), is the site at which RipX and CodV catalyze site-specific recombination reactions required for normal chromosome partitioning. Bsdif in vivo recombination did not require the B. subtilis FtsK homologues, SpoIIIE and YtpT. We also show that the presence or absence of the B. subtilis SPβ-bacteriophage, and in particular its yopP gene product, appears to strongly modulate the extent of the partitioning defects seen in codV strains and, to a lesser extent, those seen in ripX and dif strains

Unified continuum approach to crystal surface morphological relaxation

A continuum theory is used to predict scaling laws for the morphological relaxation of crystal surfaces in two independent space dimensions. The goal is to unify previously disconnected experimental observations of decaying surface profiles. The continuum description is derived from the motion of interacting atomic steps. For isotropic diffusion of adatoms across each terrace, induced adatom fluxes transverse and parallel to step edges obey different laws, yielding a tensor mobility for the continuum surface flux. The partial differential equation (PDE) for the height profile expresses an interplay of step energetics and kinetics, and aspect ratio of surface topography that plausibly unifies observations of decaying bidirectional surface corrugations. The PDE reduces to known evolution equations for axisymmetric mounds and one-dimensional periodic corrugations.Comment: 5 pages, 1 figur

Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 µm), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 µg/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

Anisotropic diffusion in continuum relaxation of stepped crystal surfaces

We study the continuum limit in 2+1 dimensions of nanoscale anisotropic diffusion processes on crystal surfaces relaxing to become flat below roughening. Our main result is a continuum law for the surface flux in terms of a new continuum-scale tensor mobility. The starting point is the Burton, Cabrera and Frank (BCF) theory, which offers a discrete scheme for atomic steps whose motion drives surface evolution. Our derivation is based on the separation of local space variables into fast and slow. The model includes: (i) anisotropic diffusion of adsorbed atoms (adatoms) on terraces separating steps; (ii) diffusion of atoms along step edges; and (iii) attachment-detachment of atoms at step edges. We derive a parabolic fourth-order, fully nonlinear partial differential equation (PDE) for the continuum surface height profile. An ingredient of this PDE is the surface mobility for the adatom flux, which is a nontrivial extension of the tensor mobility for isotropic terrace diffusion derived previously by Margetis and Kohn. Approximate, separable solutions of the PDE are discussed.Comment: 14 pages, 1 figur

Controlling Fast Chaos in Delay Dynamical Systems

We introduce a novel approach for controlling fast chaos in time-delay dynamical systems and use it to control a chaotic photonic device with a characteristic time scale of ~12 ns. Our approach is a prescription for how to implement existing chaos control algorithms in a way that exploits the system's inherent time-delay and allows control even in the presence of substantial control-loop latency (the finite time it takes signals to propagate through the components in the controller). This research paves the way for applications exploiting fast control of chaos, such as chaos-based communication schemes and stabilizing the behavior of ultrafast lasers.Comment: 4 pages, 4 figures, to be published in Physical Review Letter

How to share a quantum secret

We investigate the concept of quantum secret sharing. In a ((k,n)) threshold scheme, a secret quantum state is divided into n shares such that any k of those shares can be used to reconstruct the secret, but any set of k-1 or fewer shares contains absolutely no information about the secret. We show that the only constraint on the existence of threshold schemes comes from the quantum "no-cloning theorem", which requires that n < 2k, and, in all such cases, we give an efficient construction of a ((k,n)) threshold scheme. We also explore similarities and differences between quantum secret sharing schemes and quantum error-correcting codes. One remarkable difference is that, while most existing quantum codes encode pure states as pure states, quantum secret sharing schemes must use mixed states in some cases. For example, if k <= n < 2k-1 then any ((k,n)) threshold scheme must distribute information that is globally in a mixed state.Comment: 5 pages, REVTeX, submitted to PR

HEMODOSE: A Set of Multi-parameter Biodosimetry Tools

There continues to be important concerns of the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow (BM) injury. This is due to the fact that hematopoietic system is a vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. In this work we describe the HEMODOSE web tools, which are built upon solid physiological and pathophysiological understanding of mammalian hematopoietic systems, and rigorous coarse-grained biomathematical modeling and validation. Using single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure, these tools can estimate absorbed doses of adult victims very rapidly and accurately to assess the severity of BM radiation injury. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. HEMODOSE web tools establish robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in very late phase (up to 4 weeks) after exposure

Controlled Quantum Secret Sharing

We present a new protocol in which a secret multiqubit quantum state $\ket{\Psi}$ is shared by $n$ players and $m$ controllers, where $\ket{\Psi}$ is the encoding state of a quantum secret sharing scheme. The players may be considered as field agents responsible for carrying out a task, using the secret information encrypted in $\ket{\Psi}$, while the controllers are superiors who decide if and when the task should be carried out and who to do it. Our protocol only requires ancillary Bell states and Bell-basis measurements.Comment: 6 pages, 0 figure, RevTeX4; published version with minor change

Some Directions beyond Traditional Quantum Secret Sharing

We investigate two directions beyond the traditional quantum secret sharing (QSS). First, a restriction on QSS that comes from the no-cloning theorem is that any pair of authorized sets in an access structure should overlap. From the viewpoint of application, this places an unnatural constraint on secret sharing. We present a generalization, called assisted QSS (AQSS), where access structures without pairwise overlap of authorized sets is permissible, provided some shares are withheld by the share dealer. We show that no more than $\lambda-1$ withheld shares are required, where $\lambda$ is the minimum number of {\em partially linked classes} among the authorized sets for the QSS. Our result means that such applications of QSS need not be thwarted by the no-cloning theorem. Secondly, we point out a way of combining the features of QSS and quantum key distribution (QKD) for applications where a classical information is shared by quantum means. We observe that in such case, it is often possible to reduce the security proof of QSS to that of QKD.Comment: To appear in Physica Scripta, 7 pages, 1 figure, subsumes arXiv:quant-ph/040720

Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.

The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials