Autoselection of Cytoplasmic Yeast Virus Like Elements Encoding Toxin/Antitoxin Systems Involves a Nuclear Barrier for Immunity Gene Expression

Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE) as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle

Baryon Operators and Baryon Spectroscopy

The issues involved in a determination of the baryon resonance spectrum in lattice QCD are discussed. The variational method is introduced and the need to construct a sufficient basis of interpolating operators is emphasised. The construction of baryon operators using group-theory techniques is outlined. We find that the use both of quark-field smearing and link-field smearing in the operators is essential firstly to reduce the coupling of operators to high-frequency modes and secondly to reduce the gauge-field fluctuations in correlators. We conclude with a status report of our current investigation of baryon spectroscopy.Comment: Invited talk at Workshop on Computational Hadron Physics, Cyprus, Sept. 14-17, 200

Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells

BACKGROUND: The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury. METHODS: We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-α (TNF-α) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-α were measured by ELISA. RESULTS: Halothane pre-treated rat HECs released significantly greater TNF-α concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats. CONCLUSION: These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-α release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-α release measured following both MAA-Alb and LPS stimulation

The (LATTICE) QCD Potential and Running Coupling: How to Accurately Interpolate between Multi-Loop QCD and the String Picture

We present a simple parameterization of a running coupling constant, defined via the static potential, that interpolates between 2-loop QCD in the UV and the string prediction in the IR. Besides the usual \Lam-parameter and the string tension, the coupling depends on one dimensionless parameter, determining how fast the crossover from UV to IR behavior occurs (in principle we know how to take into account any number of loops by adding more parameters). Using a new Ansatz for the LATTICE potential in terms of the continuum coupling, we can fit quenched and unquenched Monte Carlo results for the potential down to ONE lattice spacing, and at the same time extract the running coupling to high precision. We compare our Ansatz with 1-loop results for the lattice potential, and use the coupling from our fits to quantitatively check the accuracy of 2-loop evolution, compare with the Lepage-Mackenzie estimate of the coupling extracted from the plaquette, and determine Sommer's scale $r_0$ much more accurately than previously possible. For pure SU(3) we find that the coupling scales on the percent level for $\beta\geq 6$.Comment: 47 pages, incl. 4 figures in LaTeX [Added remarks on correlated vs. uncorrelated fits in sect. 4; corrected misprints; updated references.

Digital Bridges Across Disciplinary, Practical and Pedagogical Divides: An Online Professional Master’s Program in Heritage Resource Management

Growth and diversification in heritage resource management (HRM) archaeology since the 1960s have created new demands for training the next generations of HRM leaders and for addressing persistent and counterproductive divisions between academic and applied archaeologies. The Simon Fraser University Department of Archaeology (SFU) has responded to these demands with an all-new, cohort-based, thesis-focused graduate program created by and for HRM professionals. The program’s target audience is HRM practitioners who hold Bachelor’s credentials, have initiated promising careers in HRM, and desire advanced, research-focused degrees to enable their professional capacity and upward mobility. The SFU program is structured and focused to provide intensive, predominantly online training in the four essential dimensions of HRM: law and policy, ethics and practice, business management, and research design and methods. The program has been successful through initial cohort cycles and in attracting HRM industry interest in collaboration. Industry-academic partnerships in cognate disciplines have proved effective in comparable circumstances but remain underdeveloped as bases for planning and delivering state-of-the-art training in applied archaeology and the broader field of HRM. Critical next steps in program development entail the identification of attributes of HRM futures desired by all or most HRM stakeholders and the collaborative pursuit of those desired futures

A motor association area in the depths of the central sulcus

Cells in the precentral gyrus directly send signals to the periphery to generate movement and are principally organized as a topological map of the body. We find that movement-induced electrophysiological responses from depth electrodes extend this map three-dimensionally throughout the gyrus. Unexpectedly, this organization is interrupted by a previously undescribed motor association area in the depths of the midlateral aspect of the central sulcus. This \u27Rolandic motor association\u27 (RMA) area is active during movements of different body parts from both sides of the body and may be important for coordinating complex behaviors

Ab Initio Calculation of Relativistic Corrections to the Static Interquark potential I: SU(2) Gauge Theory

We test the capability of state-of-the-art lattice techniques for a precise determination of relativistic corrections to the static interquark potential, by use of SU(2) gauge theory. Emphasis is put on the short range structure of the spin dependent potentials, with lattice resolution a ranging from a approx 0.04 fm (at beta=2.74) down to a approx 0.02 fm (at beta=2.96) on volumes of 32^4 and 48^4 lattice sites. We find a new short range Coulomb-like contribution to the spin-orbit potential V_1'.Comment: 37 pages REVTeX with 20 encapsuled ps figure

Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss.

Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE) induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2) and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT) bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO), but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT), analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures

Does the XY Model have an integrable continuum limit?

The quantum field theory describing the massive O(2) nonlinear sigma-model is investigated through two non-perturbative constructions: The form factor bootstrap based on integrability and the lattice formulation as the XY model. The S-matrix, the spin and current two-point functions, as well as the 4-point coupling are computed and critically compared in both constructions. On the bootstrap side a new parafermionic super selection sector is found; in the lattice theory a recent prediction for the (logarithmic) decay of lattice artifacts is probed.Comment: 69 pages, 18 figures. Equation (3.20) correcte

A calculation of the Lepage-Mackenzie scale for the lattice axial and vector currents

We calculate the perturbative scales (q*) for the axial and vector currents for the Wilson action, with and without tadpole improvement, using Lepage and Mackenzie's formalism. The scale for the pseudoscalar density (times the mass) is computed as well. Contrary to naive expectation, tadpole improvement reduces q* by only a small amount for the operators we consider. We also discuss the use of a nonperturbative coupling to calculate the perturbative scale.Comment: 13 pages. One postscript figur