BasinSim 1.0 A Windows-Based Watershed Modeling Package

BasinSim 1.0 for Windows is the product of a NOAA Coastal Zone Management grant (through the Virginia Coastal Resources Management Program) awarded to Drs. Ting Dai, R. L. Wetzel, I. C. Anderson, and L. W. Haas at the Virginia Institute of Marine Science, College of William and Mary in 1998. Additional support has been provided for the development and testing of this package and production of this user’s guide by grants from Virginia’s Chesapeake Bay Local Assistance Department (CBLAD). BasinSim 1.0 is a desktop simulation system that predicts sediment and nutrient loads for small to mid-sized watersheds. The simulation system is based on the Generalized Watershed Loading Functions (GWLF), a tested watershed model developed by Dr. Douglas Haith and his colleagues at Cornell University, New York (Haith and Shoemaker 1987, Haith et al. 1992). BasinSim 1.0 integrates an easy-to-use graphic Windows interface, extensive databases (land uses, population, soils, water discharge, water quality, climate, point nutrient sources, etc.), and the GWLF model (with modifications) into a single software package. It was designed to enable resource managers to visualize watershed characteristics, retrieve historic data (at the county and sub-watershed levels), manipulate land use patterns, and simulate nutrient (N, P, and organic C) and sediment loadings under various scenarios. The software will assist resource managers in making sound management decisions using the latest technology, information, and scientific knowledge. The system can also be used to educate local organizations and the general public about linkages between basinwide resource management and water quality

The Grizzly, April 22, 2010

Yesterday Marks Ursinus\u27 Fifth Annual CoSA • John Corson Announced as Ursinus Interim President • Dean Nolan Named Vice President of Student Affairs • Southeast Asian Student Association Presents Tour of Asia to Students and Faculty • John Strassburger 5K Run is a Success • The Lantern Unveiled with New Surprises • NCAA\u27s First Openly Gay Football Captain Speaks at UC • Going the Distance with a Nose • Erin Dickerson: Promoting Diversity at Ursinus • UCDC Brings a Round of Fresh Performances Tonight Through Saturday • Opinions: Discovering the Pros and Cons of Unpaid Internships; Transferring and Adapting to Life at UC; An Ursinus Student\u27s Journey to Istanbul, Turkey • UC Women\u27s Tennis Continues with Season • Softball Coaches Might Begin to Look to UC for Advicehttps://digitalcommons.ursinus.edu/grizzlynews/1812/thumbnail.jp

Not so lumpy after all: modelling the depletion of dark matter subhaloes by Milky Way-like galaxies

Among the most important goals in cosmology is detecting and quantifying small (M_(halo)≃10^(6−9) M⊙) dark matter (DM) subhaloes. Current probes around the Milky Way (MW) are most sensitive to such substructure within ∼20 kpc of the halo centre, where the galaxy contributes significantly to the potential. We explore the effects of baryons on subhalo populations in ΛCDM using cosmological zoom-in baryonic simulations of MW-mass haloes from the Latte simulation suite, part of the Feedback In Realistic Environments (FIRE) project. Specifically, we compare simulations of the same two haloes run using (1) DM-only (DMO), (2) full baryonic physics and (3) DM with an embedded disc potential grown to match the FIRE simulation. Relative to baryonic simulations, DMO simulations contain ∼2 × as many subhaloes within 100 kpc of the halo centre; this excess is ≳5 × within 25 kpc. At z = 0, the baryonic simulations are completely devoid of subhaloes down to 3×10^6M⊙ within 15 kpc of the MW-mass galaxy, and fewer than 20 surviving subhaloes have orbital pericentres <20 kpc. Despite the complexities of baryonic physics, the simple addition of an embedded central disc potential to DMO simulations reproduces this subhalo depletion, including trends with radius, remarkably well. Thus, the additional tidal field from the central galaxy is the primary cause of subhalo depletion. Subhaloes on radial orbits that pass close to the central galaxy are preferentially destroyed, causing the surviving population to have tangentially biased orbits compared to DMO predictions. Our method of embedding a potential in DMO simulations provides a fast and accurate alternative to full baryonic simulations, thus enabling suites of cosmological simulations that can provide accurate and statistical predictions of substructure populations

Attenuated reovirus displays oncolysis with reduced host toxicity

Background: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. Methods: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. Results: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. Conclusion: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy

Independent Regulation of Reovirus Membrane Penetration and Apoptosis by the μ1 ϕ Domain

Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein μ1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of μ1 indicates that the μ1 ϕ domain is sufficient to elicit a cell death response. To evaluate the contribution of the μ1 ϕ domain to the induction of apoptosis following reovirus infection, ϕ mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in ϕ diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in ϕ affect the apoptotic potential of reovirus, suggesting that ϕ initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective ϕ mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the ϕ domain of μ1 plays an important regulatory role in reovirus-induced apoptosis and disease

Bid Regulates the Pathogenesis of Neurotropic Reovirus

Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence

The oncolytic effect in vivo of reovirus on tumour cells that have survived reovirus cell killing in vitro

The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We previously reported the effective use of reovirus against lymphoid malignancies, including the Burkitt's lymphoma cell line Raji. Here we isolated in vitro persistently infected (PI) Raji cells, and cells ‘cured' of persistent reovirus infection (‘cured' cells). Both PI and cured Raji cells resisted reovirus infection and cell killing in vitro. In vivo, the PI cells were non-tumorigenic in SCID mice, but cured cells regained the parental cells' ability to form tumours. Tumour xenografts from the cured cells, however, were highly susceptible to reovirus oncolysis in vivo. This susceptibility was due to the proteolytic environment within tumours that facilitates reovirus infection and cell killing. Our results show that persistent infection by reovirus impedes tumour development and that although PI cells cleared of reovirus are tumorigenic, they are killed upon rechallenge with reovirus. Both the PI and cured states are therefore not likely to be significant barriers to reovirus oncolytic therapy

A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor

Background Trypanosoma cruzi is a parasitic protist that causes Chagas disease, which is prevalent in Latin America. Because of the unavailability of an effective drug or vaccine, and because about 8 million people are infected with the parasite worldwide, the development of novel drugs demands urgent attention. T. cruzi infects a wide variety of mammalian nucleated cells, with a preference for myocardial cells. Non-dividing trypomastigotes in the bloodstream infect host cells where they are transformed into replication-capable amastigotes. The amastigotes revert to trypomastigotes (trypomastigogenesis) before being shed out of the host cells. Although trypomastigote transformation is an essential process for the parasite, the molecular mechanisms underlying this process have not yet been clarified, mainly because of the lack of an assay system to induce trypomastigogenesis in vitro. Methodology/Principal Findings Cultivation of amastigotes in a transformation medium composed of 80% RPMI-1640 and 20% Grace\u27s Insect Medium mediated their transformation into trypomastigotes. Grace\u27s Insect Medium alone also induced trypomastigogenesis. Furthermore, trypomastigogenesis was induced more efficiently in the presence of fetal bovine serum. Trypomastigotes derived from in vitro trypomastigogenesis were able to infect mammalian host cells as efficiently as tissue-culture-derived trypomastigotes (TCT) and expressed a marker protein for TCT. Using this assay system, we demonstrated that T. cruzi inositol 1,4,5-trisphosphate receptor (TcIP3R) - an intracellular Ca2+ channel and a key molecule involved in Ca2+ signaling in the parasite - is important for the transformation process. Conclusion/Significance Our findings provide a new tool to identify the molecular mechanisms of the amastigote-totrypomastigote transformation, leading to a new strategy for drug development against Chagas disease