Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico

Malaria is one of the world’s most common and serious diseases causing death of about 3 million people each year. Its most severe occurrence is caused by the protozoan Plasmodium falciparum. Biomedical research could enable treating the disease by effectively and specifically targeting essential enzymes of this parasite. However, the parasite has developed resistance to existing drugsmaking it indispensable to discover new drugs. We have established a simple computational tool which analyses the topology of the metabolic network of P. falciparum to identify essential enzymes as possible drug targets.Weinvestigated the essentiality of a reaction in the metabolic network by deleting (knocking-out) such a reaction in silico. The algorithmselected neighbouring compounds of the investigated reaction that had to be produced by alternative biochemical pathways. Using breadth first searches, we tested qualitatively if these products could be generated by reactions that serve as potential deviations of the metabolic flux. With this we identified 70 essential reactions. Our results were compared with a comprehensive list of 38 targets of approved malaria drugs. When combining our approach with an in silico analysis performed recently [Yeh, I., Hanekamp, T., Tsoka, S., Karp, P.D., Altman, R.B., 2004. Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Res. 14, 917–924] we could improve the precision of the prediction results. Finally we present a refined list of 22 new potential candidate targets for P. falciparum, half of which have reasonable evidence to be valid targets against micro-organisms and cancer

Program on stimulating operational private sector use of Earth observation satellite information

Ideas for new businesses specializing in using remote sensing and computerized spatial data systems were developd. Each such business serves as an 'information middleman', buying raw satellite or aircraft imagery, processing these data, combining them in a computer system with customer-specific information, and marketing the resulting information products. Examples of the businesses the project designed are: (1) an agricultural facility site evaluation firm; (2) a mass media grocery price and supply analyst and forecaster; (3) a management service for privately held woodlots; (4) a brokerage for insulation and roofing contractors, based on infrared imagery; (5) an expanded real estate information service. In addition, more than twenty-five other commercially attractive ideas in agribusiness, forestry, mining, real estate, urban planning and redevelopment, and consumer information were created. The commercial feasibility of the five business was assessed. This assessment included market surveys, revenue projections, cost analyses, and profitability studies. The results show that there are large and enthusiastic markets willing to pay for the services these businesses offer, and that the businesses could operate profitably

Program on stimulating operational private sector use of Earth observation satellite data

There are no author-identified significant results in this report

Capillary pressure of van der Waals liquid nanodrops

The dependence of the surface tension on a nanodrop radius is important for the new-phase formation process. It is demonstrated that the famous Tolman formula is not unique and the size-dependence of the surface tension can distinct for different systems. The analysis is based on a relationship between the surface tension and disjoining pressure in nanodrops. It is shown that the van der Waals interactions do not affect the new-phase formation thermodynamics since the effect of the disjoining pressure and size-dependent component of the surface tension cancel each other.Comment: The paper is dedicated to the 80th anniversary of A.I. Rusano

Coordinated mm/sub-mm observations of Sagittarius A* in May 2007

At the center of the Milky Way, with a distance of ~8 kpc, the compact source Sagittarius A* (SgrA*) can be associated with a super massive black hole of ~4x10^6 solar masses. SgrA* shows strong variability from the radio to the X-ray wavelength domains. Here we report on simultaneous NIR/sub-millimeter/X-ray observations from May 2007 that involved the NACO adaptive optics (AO) instrument at the European Southern Observatory's Very Large Telescope, the Australian Telescope Compact Array (ATCA), the US mm-array CARMA, the IRAM 30m mm-telescope, and other telescopes. We concentrate on the time series of mm/sub-mm data from CARMA, ATCA, and the MAMBO bolometer at the IRAM 30m telescope.Comment: 7 pages, 3 figures, contribution for the conference "The Universe under the Microscope" (AHAR 2008), to be published in Journal of Physics: Conference Series by Institute of Physics Publishin

Lunar Outgassing, Transient Phenomena and The Return to The Moon, I: Existing Data

Herein the transient lunar phenomena (TLP) report database is subjected to a discriminating statistical filter robust against sites of spurious reports, and produces a restricted sample that may be largely reliable. This subset is highly correlated geographically with the catalog of outgassing events seen by the Apollo 15, 16 and Lunar Prospector alpha-particle spectrometers for episodic Rn-222 gas release. Both this robust TLP sample and even the larger, unfiltered sample are highly correlated with the boundary between mare and highlands, as are both deep and shallow moonquakes, as well as Po-210, a long-lived product of Rn-222 decay and a further tracer of outgassing. This offers another significant correlation relating TLPs and outgassing, and may tie some of this activity to sagging mare basalt plains (perhaps mascons). Additionally, low-level but likely significant TLP activity is connected to recent, major impact craters (while moonquakes are not), which may indicate the effects of cracks caused by the impacts, or perhaps avalanches, allowing release of gas. The majority of TLP (and Rn-222) activity, however, is confined to one site that produced much of the basalt in the Procellarum Terrane, and it seems plausible that this TLP activity may be tied to residual outgassing from the formerly largest volcanic ffusion sites from the deep lunar interior. With the coming in the next few years of robotic spacecraft followed by human exploration, the study of TLPs and outgassing is both promising and imperiled. We will have an unprecedented pportunity to study lunar outgassing, but will also deal with a greater burden of anthropogenic lunar gas than ever produced. There is a pressing need to study lunar atmosphere and its sources while still pristine. [Abstract abridged.]Comment: 35 pages, 3 figures, submitted to Icarus. Other papers in series found at http://www.astro.columbia.edu/~arlin/TLP

Correlation induced switching of local spatial charge distribution in two-level system

We present theoretical investigation of spatial charge distribution in the two-level system with strong Coulomb correlations by means of Heisenberg equations analysis for localized states total electron filling numbers taking into account pair correlations of local electron density. It was found that tunneling current through nanometer scale structure with strongly coupled localized states causes Coulomb correlations induced spatial redistribution of localized charges. Conditions for inverse occupation of two-level system in particular range of applied bias caused by Coulomb correlations have been revealed. We also discuss possibility of charge manipulation in the proposed system.Comment: 6 pages, 4 figures Submitted to JETP Letter

The performance of GridPix detectors

A GridPix detector is a gaseous detector capable of detecting individual single primary electrons from ionizing particles. Such a detector consists of a pixel chip as active anode covered with a thin layer of silicon rich silicon nitride (SiRN) for protection against discharges, an integrated amplification grid (InGrid), applied on top of the chip by wafer post processing techniques, and a cathode plane. The drift region is between the grid and cathode while the gas gain occurs between the chip and the grid. The discharge quenching properties of the SiRN layer have been determined as well as the relation on grid capacitance, grid voltage and gas mixture. Part of the detectors in this report were of the type Gossip, a GridPix detector with a drift gap of ∼1 mm. Using such thin drift layer, one may consider this detector as a replacement for a silicon pixel detector. The performance of three Gossip detectors has been investigated by measurements in a test beam at CERN

Transport Spectroscopy of Symmetry-Broken Insulating States in Bilayer Graphene

The flat bands in bilayer graphene(BLG) are sensitive to electric fields E\bot directed between the layers, and magnify the electron-electron interaction effects, thus making BLG an attractive platform for new two-dimensional (2D) electron physics[1-5]. Theories[6-16] have suggested the possibility of a variety of interesting broken symmetry states, some characterized by spontaneous mass gaps, when the electron-density is at the carrier neutrality point (CNP). The theoretically proposed gaps[6,7,10] in bilayer graphene are analogous[17,18] to the masses generated by broken symmetries in particle physics and give rise to large momentum-space Berry curvatures[8,19] accompanied by spontaneous quantum Hall effects[7-9]. Though recent experiments[20-23] have provided convincing evidence of strong electronic correlations near the CNP in BLG, the presence of gaps is difficult to establish because of the lack of direct spectroscopic measurements. Here we present transport measurements in ultra-clean double-gated BLG, using source-drain bias as a spectroscopic tool to resolve a gap of ~2 meV at the CNP. The gap can be closed by an electric field E\bot \sim13 mV/nm but increases monotonically with a magnetic field B, with an apparent particle-hole asymmetry above the gap, thus providing the first mapping of the ground states in BLG.Comment: 4 figure

Ultra-low carrier concentration and surface dominant transport in Sb-doped Bi2Se3 topological insulator nanoribbons

A topological insulator is a new state of matter, possessing gapless spin-locking surface states across the bulk band gap which has created new opportunities from novel electronics to energy conversion. However, the large concentration of bulk residual carriers has been a major challenge for revealing the property of the topological surface state via electron transport measurement. Here we report surface state dominated transport in Sb-doped Bi2Se3 nanoribbons with very low bulk electron concentrations. In the nanoribbons with sub-10nm thickness protected by a ZnO layer, we demonstrate complete control of their top and bottom surfaces near the Dirac point, achieving the lowest carrier concentration of 2x10^11/cm2 reported in three-dimensional (3D) topological insulators. The Sb-doped Bi2Se3 nanostructures provide an attractive materials platform to study fundamental physics in topological insulators, as well as future applications.Comment: 5 pages, 4 figures, 1 tabl