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

Cyberprints: Identifying Cyber Attackers by Feature Analysis

The problem of attributing cyber attacks is one of increasing importance. Without a solid method of demonstrating the origin of a cyber attack, any attempts to deter would-be cyber attackers are wasted. Existing methods of attribution make unfounded assumptions about the environment in which they will operate: omniscience (the ability to gather, store, and analyze any data relevant to an attack), omnipresence (the ability to place sensors wherever necessary regardless of jurisdiction or ownership), and \emph{a priori} positioning (ignorance of the real costs of placing sensors in speculative locations). The reality is that attribution must be able to occur with only the information available directly to a forensic analyst, gathered within the target network, using budget-conscious placement of sensors and analyzers. These assumptions require a new form of attribution. This work evaluates the use of a number of network-level features as an analog of stylistic markers in literature. We find that principal component analysis is not a useful tool in analyzing these features. We are, however, able to perform Kolmogorov-Smirnov comparisons upon the feature set distributions directly to find a subset of the examined features which hold promise for forming the foundation of a \emph{Cyberprint}. This foundation could be used to examine other potential features for discriminatory power, and to establish a new direction for network forensic analysis

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

Studies of the genetics and physiology of a nitrate non-utilizing strain of Neurospora

Studies of the genetics andphysiology of a nitrate non-utilizing strain of Neurospor

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

Neural Attention and Evaluative Responses to Gay and Lesbian Couples

The goal of the current study was to examine whether differential neural attentional capture and evaluative responses for out-group homosexual relative to in-group heterosexual targets occur during social categorization. To this end, 36 heterosexual participants were presented with pictures of heterosexual and homosexual couples in a picture-viewing task that was designed to assess implicit levels of discomfort toward homosexuality and explicit evaluations of pleasantness toward the images. Neural activity in the form of electroencephalogram was recorded during the presentation of the pictures, and event-related potentials resulting from these stimuli were examined. Participants also completed questionnaires that assessed the degree to which they socialized with gays and lesbians. Results demonstrated that relative to straight couples, larger P2 amplitude was observed in response to gay but not to lesbian couples. However, both gay and lesbian couples yielded a larger late positive potential than straight couples. Moreover, the degree to which participants differentially directed early neural attention to out-group lesbian versus in-group straight couples was related to their familiarity with homosexual individuals. This work, which provides an initial understanding of the neural underpinnings of attention toward homosexual couples, suggests that differences in the processing of sexual orientation can occur as early as 200 ms and may be moderated by familiarity

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

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