The broadly conserved regulator PhoP links pathogen virulence and membrane potential in Escherichia coli

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87159/1/j.1365-2958.2011.07804.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87159/2/MMI_7804_sm_FigS1-4-TabS1.pd

The Atacama Cosmology Telescope: The LABOCA/ACT Survey of Clusters at All Redshifts

We present a multi-wavelength analysis of eleven Sunyaev Zel'dovich effect (SZE)-selected galaxy clusters (ten with new data) from the Atacama Cosmology Telescope (ACT) southern survey. We have obtained new imaging from the Large APEX Bolometer Camera (345GHz; LABOCA) on the Atacama Pathfinder EXperiment (APEX) telescope, the Australia Telescope Compact Array (2.1GHz; ATCA), and the Spectral and Photometric Imaging Receiver (250, 350, and $500\,\rm\mu m$; SPIRE) on the Herschel Space Observatory. Spatially-resolved 345GHz SZE increments with integrated S/N > 5 are found in six clusters. We compute 2.1GHz number counts as a function of cluster-centric radius and find significant enhancements in the counts of bright sources at projected radii $\theta < \theta_{2500}$. By extrapolating in frequency, we predict that the combined signals from 2.1GHz-selected radio sources and 345GHz-selected SMGs contaminate the 148GHz SZE decrement signal by ~5% and the 345GHz SZE increment by ~18%. After removing radio source and SMG emission from the SZE signals, we use ACT, LABOCA, and (in some cases) new Herschel SPIRE imaging to place constraints on the clusters' peculiar velocities. The sample's average peculiar velocity relative to the cosmic microwave background is $153\pm 383\,\rm km\,s^{-1}$.Comment: 19 pages, 11 figures, Accepted for Publication in The Astrophysical Journa

Coarse Woody Debris Decomposition Assessment Tool: Model Validation and Application

Coarse woody debris (CWD) is a significant component of the forest biomass pool; hence a model is warranted to predict CWD decomposition and its role in forest carbon (C) and nutrient cycling under varying management and climatic conditions. A process-based model, CWDDAT (Coarse Woody Debris Decomposition Assessment Tool) was calibrated and validated using data from the FACE (Free Air Carbon Dioxide Enrichment) Wood Decomposition Experiment utilizing pine (Pinus taeda), aspen (Populous tremuloides) and birch (Betula papyrifera) on nine Experimental Forests (EF) covering a range of climate, hydrology, and soil conditions across the continental USA. The model predictions were evaluated against measured FACE log mass loss over 6 years. Four widely applied metrics of model performance demonstrated that the CWDDAT model can accurately predict CWD decomposition. The R2 (squared Pearson’s correlation coefficient) between the simulation and measurement was 0.80 for the model calibration and 0.82 for the model validation (P\u3c0.01). The predicted mean mass loss from all logs was 5.4% lower than the measured mass loss and 1.4% lower than the calculated loss. The model was also used to assess the decomposition of mixed pine-hardwood CWD produced by Hurricane Hugo in 1989 on the Santee Experimental Forest in South Carolina, USA. The simulation reflected rapid CWD decomposition of the forest in this subtropical setting. The predicted dissolved organic carbon (DOC) derived from the CWD decomposition and incorporated into the mineral soil averaged 1.01 g C m-2 y-1 over the 30 years. The main agents for CWD mass loss were fungi (72.0%) and termites (24.5%), the remainder was attributed to a mix of other wood decomposers. These findings demonstrate the applicability of CWDDAT for large-scale assessments of CWD dynamics, and fine-scale considerations regarding the fate of CWD carbon

The influence of hand positions on biomechanical injury risk factors at the wrist joint during the round-off skills in female gymnastics

The aim of this study was to examine the biomechanical injury risk factors at the wrist, including joint kinetics, kinematics and stiffness in the first and second contact limb for parallel and T-shape round-off (RO) techniques. Seven international-level female gymnasts performed 10 trials of the RO to back handspring with parallel and T-shape hand positions. Synchronised kinematic (3D motion analysis system; 247 Hz) and kinetic (two force plates; 1235 Hz) data were collected for each trial. A two-way repeated measure analysis of variance (ANOVA) assessed differences in the kinematic and kinetic parameters between the techniques for each contact limb. The main findings highlighted that in both the RO techniques, the second contact limb wrist joint is exposed to higher mechanical loads than the first contact limb demonstrated by increased axial compression force and loading rate. In the parallel technique, the second contact limb wrist joint is exposed to higher axial compression load. Differences between wrist joint kinetics highlight that the T-shape technique may potentially lead to reducing these bio-physical loads and consequently protect the second contact limb wrist joint from overload and biological failure. Highlighting the biomechanical risk factors facilitates the process of technique selection making more objective and safe

Wigner's little group and Berry's phase for massless particles

The ``little group'' for massless particles (namely, the Lorentz transformations $\Lambda$ that leave a null vector invariant) is isomorphic to the Euclidean group E2: translations and rotations in a plane. We show how to obtain explicitly the rotation angle of E2 as a function of $\Lambda$ and we relate that angle to Berry's topological phase. Some particles admit both signs of helicity, and it is then possible to define a reduced density matrix for their polarization. However, that density matrix is physically meaningless, because it has no transformation law under the Lorentz group, even under ordinary rotations.Comment: 4 pages revte

Nitrosylcobalamin Potentiates the Anti-Neoplastic Effects of Chemotherapeutic Agents via Suppression of Survival Signaling

Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-kappaB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy.Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.Eighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.The use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-kappaB or AKT

Ubiquitäres Computing. Das »Internet der Dinge« - Grundlagen, Anwendungen, Folgen

Ubiquitäres Computing - die komplexe elektronische Vernetzung von Dingen, die kommunizieren - gilt weltweit als ein erfolgversprechender Innovationspfad. Intensive FuE-Aktivitäten und politische Strategien gelten dem Ziel, praxistaugliche Technologien und Anwendungen zu befördern. Wo stehen wir augenblicklich auf dem Weg zum »Internet der Dinge«? Welche praktischen Projekte zeigen bereits jetzt das Potenzial auf, das mit der Umsetzung der Grundidee des Ubiquitären Computings ausgeschöpft werden kann? Welche technischen, rechtlichen und gesellschaftlichen Herausforderungen müssen dazu bewältigt werden - und worin kann der Beitrag der Politik bestehen? Die Autoren analysieren im Lichte dieser Fragen den Status quo und die Perspektiven des Ubiquitären Computings und illustrieren ihre Befunde an Beispielen u.a. aus Handel, Logistik und Gesundheitswesen. die faszinierende »Heinzelmännchentechnologie« des Ubiquitären Computings muss allerdings von den Beteiligten in Wirtschaft, Gesellschaft und Politik noch umfassend fit gemacht werden, sollen ihre Anwendungen tatsächlich wirtschaftlich attraktiv, sozial verträglich sowie hilfreich bei der Bewältigung gesellschaftlicher Probleme werden

Non-Equilibrium Large N Yukawa Dynamics: marching through the Landau pole

The non-equilibrium dynamics of a Yukawa theory with N fermions coupled to a scalar field is studied in the large N limit with the goal of comparing the dynamics predicted from the renormalization group improved effective potential to that obtained including the fermionic backreaction. The effective potential is of the Coleman-Weinberg type. Its renormalization group improvement is unbounded from below and features a Landau pole. When viewed self-consistently, the initial time singularity does not arise. The different regimes of the dynamics of the fully renormalized theory are studied both analytically and numerically. Despite the existence of a Landau pole in the model, the dynamics of the mean field is smooth as it passes the location of the pole. This is a consequence of a remarkable cancellation between the effective potential and the dynamical chiral condensate. The asymptotic evolution is effectively described by a quartic upright effective potential. In all regimes, profuse particle production results in the formation of a dense fermionic plasma with occupation numbers nearly saturated up to a scale of the order of the mean field. This can be interpreted as a chemical potential. We discuss the implications of these results for cosmological preheating.Comment: 36 pages, 14 figures, LaTeX, submitted to Physical Review

Fungal endophytes and origins of decay in beech (Fagus sylvatica) sapwood

Sapwood comprises much above-ground forest biomass, but its mycobiome in living trees is largely unknown. Here, we characterize the endophytic fungal communities of the functional sapwood of young and mature living beech trees (Fagus sylvatica) at multiple scales, from within individual trees to woodland sites across the southern United Kingdom. Fungal community composition was determined using both culture-based and molecular approaches across two loci. Wood decay fungi, including those that cause heart rot, were detected in approximately 80% of all samples. Fungal community composition differed according to the survey approach (high throughput sequencing vs. isolation of fungi into culture) and between geographic location and individual trees, but no significant patterns were detected at different heights in individual trees or around their circumferences. ITS and LSU sequencing detected more distinct taxa than culturing. However, LSU primers yielded more OTUs than did ITS primers, though both identified unique OTUs. This highlights the importance of multiple survey approaches, including multiple primer pairs, for better characterisation of communities and confidence in results of endophyte studies

Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma

Multiple myeloma cells secrete more disulfide bond–rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell–based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow–sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active-site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma