The Clarens web services architecture

Clarens is a uniquely flexible web services infrastructure providing a unified access protocol to a diverse set of functions useful to the HEP community. It uses the standard HTTP protocol combined with application layer, certificate based authentication to provide single sign-on to individuals, organizations and hosts, with fine-grained access control to services, files and virtual organization (VO) management. This contribution describes the server functionality, while client applications are described in a subsequent talk.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 6 pages, LaTeX, 4 figures, PSN MONT00

Clarens Client and Server Applications

Several applications have been implemented with access via the Clarens web service infrastructure, including virtual organization management, JetMET physics data analysis using relational databases, and Storage Resource Broker (SRB) access. This functionality is accessible transparently from Python scripts, the Root analysis framework and from Java applications and browser applets.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, LaTeX, no figures, PSN TUCT00

Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid

<p>Abstract</p> <p>Background</p> <p>Due to the global occurrence of multi-drug-resistant malarial parasites (<it>Plasmodium falciparum</it>), the anti-malarial drug most effective against malaria is artemisinin, a natural product (sesquiterpene lactone endoperoxide) extracted from sweet wormwood (<it>Artemisia annua</it>). However, artemisinin is in short supply and unaffordable to most malaria patients. Artemisinin can be semi-synthesized from its precursor artemisinic acid, which can be synthesized from simple sugars using microorganisms genetically engineered with genes from <it>A. annua</it>. In order to develop an industrially competent yeast strain, detailed analyses of microbial physiology and development of gene expression strategies are required.</p> <p>Results</p> <p>Three plant genes coding for amorphadiene synthase, amorphadiene oxidase (<it>AMO </it>or <it>CYP71AV1</it>), and cytochrome P450 reductase, which in concert divert carbon flux from farnesyl diphosphate to artemisinic acid, were expressed from a single plasmid. The artemisinic acid production in the engineered yeast reached 250 μg mL^-1in shake-flask cultures and 1 g L^-1in bio-reactors with the use of <it>Leu2d </it>selection marker and appropriate medium formulation. When plasmid stability was measured, the yeast strain synthesizing amorphadiene alone maintained the plasmid in 84% of the cells, whereas the yeast strain synthesizing artemisinic acid showed poor plasmid stability. Inactivation of AMO by a point-mutation restored the high plasmid stability, indicating that the low plasmid stability is not caused by production of the AMO protein but by artemisinic acid synthesis or accumulation. Semi-quantitative reverse-transcriptase (RT)-PCR and quantitative real time-PCR consistently showed that pleiotropic drug resistance (<it>PDR</it>) genes, belonging to the family of ATP-Binding Cassette (ABC) transporter, were massively induced in the yeast strain producing artemisinic acid, relative to the yeast strain producing the hydrocarbon amorphadiene alone. Global transcriptional analysis by yeast microarray further demonstrated that the induction of drug-resistant genes such as ABC transporters and major facilitator superfamily (MSF) genes is the primary cellular stress-response; in addition, oxidative and osmotic stress responses were observed in the engineered yeast.</p> <p>Conclusion</p> <p>The data presented here suggest that the engineered yeast producing artemisinic acid suffers oxidative and drug-associated stresses. The use of plant-derived transporters and optimizing AMO activity may improve the yield of artemisinic acid production in the engineered yeast.</p

CANDELS Observations Of The Structural Properties Of Cluster Galaxies At Z=1.62

We discuss the structural and morphological properties of galaxies in a z = 1.62 proto-cluster using near-IR imaging data from Hubble Space Telescope Wide Field Camera 3 data of the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS). The cluster galaxies exhibit a clear color-morphology relation: galaxies with colors of quiescent stellar populations generally have morphologies consistent with spheroids, and galaxies with colors consistent with ongoing star formation have disk-like and irregular morphologies. The size distribution of the quiescent cluster galaxies shows a deficit of compact (less than or similar to 1 kpc), massive galaxies compared to CANDELS field galaxies at z = 1.6. As a result, the cluster quiescent galaxies have larger average effective sizes compared to field galaxies at fixed mass at greater than 90% significance. Combined with data from the literature, the size evolution of quiescent cluster galaxies is relatively slow from z similar or equal to 1.6 to the present, growing as (1 + z)(-0.6 +/- 0.1). If this result is generalizable, then it implies that physical processes associated with the denser cluster region seem to have caused accelerated size growth in quiescent galaxies prior to z = 1.6 and slower subsequent growth at z < 1.6 compared to galaxies in the lower density field. The quiescent cluster galaxies at z = 1.6 have higher ellipticities compared to lower redshift samples at fixed mass, and their surface-brightness profiles suggest that they contain extended stellar disks. We argue that the cluster galaxies require dissipationless (i.e., gas-poor or "dry") mergers to reorganize the disk material and to match the relations for ellipticity, stellar mass, size, and color of early-type galaxies in z < 1 clusters.NASA NAS5-26555HST GO-12060NASA through from the Space Telescope Science Institute GO-12060European Research CouncilRoyal SocietyTexas AM UniversityGeorge P. and Cynthia Woods Institute for Fundamental Physics and AstronomyAstronom

Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms

Redox cycling of extracellular electron shuttles can enable the metabolic activity of subpopulations within multicellular bacterial biofilms that lack direct access to electron acceptors or donors. How these shuttles catalyze extracellular electron transfer (EET) within biofilms without being lost to the environment has been a long-standing question. Here, we show that phenazines mediate efficient EET through interactions with extracellular DNA (eDNA) in Pseudomonas aeruginosa biofilms. Retention of pyocyanin (PYO) and phenazine carboxamide in the biofilm matrix is facilitated by eDNA binding. In vitro, different phenazines can exchange electrons in the presence or absence of DNA and can participate directly in redox reactions through DNA. In vivo, biofilm eDNA can also support rapid electron transfer between redox active intercalators. Together, these results establish that PYO:eDNA interactions support an efficient redox cycle with rapid EET that is faster than the rate of PYO loss from the biofilm

Response of the Antarctic Stratosphere to Warm Pool EI Nino Events in the GEOS CCM

A new type of EI Nino event has been identified in the last decade. During "warm pool" EI Nino (WPEN) events, sea surface temperatures (SSTs) in the central equatorial Pacific are warmer than average. The EI Nino signal propagates poleward and upward as large-scale atmospheric waves, causing unusual weather patterns and warming the polar stratosphere. In austral summer, observations show that the Antarctic lower stratosphere is several degrees (K) warmer during WPEN events than during the neutral phase of EI Nino/Southern Oscillation (ENSO). Furthermore, the stratospheric response to WPEN events depends of the direction of tropical stratospheric winds: the Antarctic warming is largest when WPEN events are coincident with westward winds in the tropical lower and middle stratosphere i.e., the westward phase of the quasi-biennial oscillation (QBO). Westward winds are associated with enhanced convection in the subtropics, and with increased poleward wave activity. In this paper, a new formulation of the Goddard Earth Observing System Chemistry-Climate Model, Version 2 (GEOS V2 CCM) is used to substantiate the observed stratospheric response to WPEN events. One simulation is driven by SSTs typical of a WPEN event, while another simulation is driven by ENSO neutral SSTs; both represent a present-day climate. Differences between the two simulations can be directly attributed to the anomalous WPEN SSTs. During WPEN events, relative to ENSO neutral, the model simulates the observed increase in poleward planetary wave activity in the South Pacific during austral spring, as well as the relative warming of the Antarctic lower stratosphere in austral summer. However, the modeled response to WPEN does not depend on the phase of the QBO. The modeled tropical wind oscillation does not extend far enough into the lower stratosphere and upper troposphere, likely explaining the model's insensitivity to the phase of the QBO during WPEN events

Associations of Blood Pressure and&nbsp;Cholesterol Levels During Young&nbsp;Adulthood With Later&nbsp;Cardiovascular Events.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL&nbsp;≥100&nbsp;mg/dl (compared with&nbsp;&lt;100&nbsp;mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP&nbsp;≥130&nbsp;mm&nbsp;Hg (compared with&nbsp;&lt;120&nbsp;mm&nbsp;Hg) was associated with a 37% increased risk for HF, and young adult DBP&nbsp;≥80&nbsp;mm&nbsp;Hg (compared with&nbsp;&lt;80&nbsp;mm&nbsp;Hg) was associated with a 21% increased risk.ConclusionsCumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with&nbsp;increased CVD risks in later life, independent of later adult exposures

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered complement regulation. We report three cases of kidney limited TMA associated with benign paraproteins that had no other detectable cause for the TMA, representing cases of MGRS. Two of the cases are receiving clone directed therapy, and none are receiving eculizumab. We discuss in detail the pathophysiological basis for this possible association. Our approach to therapy involves first ruling out other causes of TMA as well as an underlying B-cell malignancy that would necessitate direct treatment. Otherwise, clone directed therapy should be considered. If refractory to such therapy or the disease is severe and multisystemic, C5 inhibition (eculizumab or ravulizumab) may be indicated as well

Effects of Noise on Ecological Invasion Processes: Bacteriophage-mediated Competition in Bacteria

Pathogen-mediated competition, through which an invasive species carrying and transmitting a pathogen can be a superior competitor to a more vulnerable resident species, is one of the principle driving forces influencing biodiversity in nature. Using an experimental system of bacteriophage-mediated competition in bacterial populations and a deterministic model, we have shown in [Joo et al 2005] that the competitive advantage conferred by the phage depends only on the relative phage pathology and is independent of the initial phage concentration and other phage and host parameters such as the infection-causing contact rate, the spontaneous and infection-induced lysis rates, and the phage burst size. Here we investigate the effects of stochastic fluctuations on bacterial invasion facilitated by bacteriophage, and examine the validity of the deterministic approach. We use both numerical and analytical methods of stochastic processes to identify the source of noise and assess its magnitude. We show that the conclusions obtained from the deterministic model are robust against stochastic fluctuations, yet deviations become prominently large when the phage are more pathological to the invading bacterial strain.Comment: 39 pages, 7 figure

New Low Accretion-Rate Magnetic Binary Systems and their Significance for the Evolution of Cataclysmic Variables

Discoveries of two new white dwarf plus M star binaries with striking optical cyclotron emission features from the Sloan Digital Sky Survey (SDSS) brings to six the total number of X-ray faint, magnetic accretion binaries that accrete at rates < 10^{-13} Msun/yr, or <1% of the values normally encountered in cataclysmic variables. This fact, coupled with donor stars that underfill their Roche lobes and very cool white dwarfs, brand the binaries as post common-envelope systems whose orbits have not yet decayed to the point of Roche-lobe contact. They are pre-magnetic CVs, or pre-Polars. The systems exhibit spin/orbit synchronism and apparently accrete by efficient capture of the stellar wind from the secondary star, a process that has been dubbed a ``magnetic siphon''. Because of this, period evolution of the binaries will occur solely by gravitational radiation, which is very slow for periods >3 hr. Optical surveys for the cyclotron harmonics appear to be the only means of discovery, so the space density of pre-Polars could rival that of Polars, and the binaries provide an important channel of progenitors (in addition to the asynchronous Intermediate Polars). Both physical and SDSS observational selection effects are identified that may help to explain the clumping of all six systems in a narrow range of magnetic field strength around 60 MG.Comment: 25 pages, 13 figures, Accepted to Ap