MODELING SEDIMENT TRAPPING IN A VEGETATIVE FILTER ACCOUNTING FOR CONVERGING OVERLAND FLOW

Vegetative filters (VF) are used to remove sediment and other pollutants from overland flow. When modeling the hydrology of VF, it is often assumed that overland flow is planar, but our research indicates that it can be two-dimensional with converging and diverging pathways. Our hypothesis is that flow convergence will negatively influence the sediment trapping capability of VF. The objectives were to develop a two-dimensional modeling approach for estimating sediment trapping in VF and to investigate the impact of converging overland flow on sediment trapping by VF. In this study, the performance of a VF that has field-scale flow path lengths with uncontrolled flow direction was quantified using field experiments and hydrologic modeling. Simulations of water flow processes were performed using the physically based, distributed model MIKE SHE. A modeling approach that predicts sediment trapping and accounts for converging and diverging flow was developed based on the University of Kentucky sediment filtration model. The results revealed that as flow convergence increases, filter performance decreases, and the impacts are greater at higher flow rates and shorter filter lengths. Convergence that occurs in the contributing field (in-field) upstream of the buffer had a slightly greater impact than convergence that occurred in the filter (in-filter). An area-based convergence ratio was defined that relates the actual flow area in a VF to the theoretical flow area without flow convergence. When the convergence ratio was 0.70, in-filter convergence caused the sediment trapping efficiency to be reduced from 80% for the planar flow condition to 64% for the converging flow condition. When an equivalent convergence occurred in-field, the sediment trapping efficiency was reduced to 57%. Thus, not only is convergence important but the location where convergence occurs can also be important

Prevalence and co-infection of Toxoplasma gondii and Neospora caninum in Apodemus sylvaticus in an area relatively free of cats

The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%–47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%–67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses frompregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%–6·66%); M. domesticus: 3·08% (95% CI: 0·11%–6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems

High Throughput siRNA Screening Identifies Phosphatidylinositol 3-kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions.

High throughput siRNA screening is a useful methodology to identify cellular factors required for virus replication. Here we utilized a high throughput siRNA screen based on detection of a viral antigen by microscopy to interrogate cellular protein kinases and phosphatases for their importance during human cytomegalovirus (HCMV) replication, and identified the Class II Phosphatidylinositol 3-kinase PI3K-C2A as being involved in HCMV replication. Confirming this observation, infected cells treated with either pooled or individual siRNAs targeting PI3K-C2A mRNA produced approximately 10-fold less infectious virus compared to controls. Western blotting and quantitative PCR analysis of infected cells treated with siRNAs indicated that depletion of PI3K-C2A slightly reduced accumulation of late, but not immediate-early or early, viral antigens and had no appreciable effect of viral DNA synthesis. Analysis of siRNA treated cells by electron microscopy and western blotting indicated that PI3K-C2A was not required for production of viral capsids, but did lead to increased numbers of enveloped capsids in the cytoplasm that had undergone secondary envelopment and reduction of viral particles exiting the cell. Therefore, PI3K-C2A is a factor important for HCMV replication and has a role in production of HCMV virions. IMPORTANCE: There is limited information about the cellular factors required for human cytomegalovirus (HCMV) replication. Therefore, to identify proteins involved in HCMV replication we developed a methodology to conduct a high throughput siRNA screen in HCMV infected cells. From our screening data we focused our studies on the top "hit" from our screen, the lipid kinase phosphatidylinositol 3-kinase Class II Alpha (PI3K-C2A), as its role in HCMV replication was unknown. Interestingly, we found that PI3K-C2A is important for the production of HCMV virions and is involved in virion production after secondary envelopment of viral capsids, the encapsidation of HCMV capsids by a lipid bilayer that occurs before virions exit the cell

P3‐473: Service need among individuals with mild cognitive impairment and Alzheimer’s disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152600/1/alzjjalz2008052044.pd

Deletion of SA β-Gal+ Cells Using Senolytics Improves Muscle Regeneration in Old Mice

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl2 or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice and increased similarly 7 days following injury in both age groups, with no effect of D+Q. Most SA β-Gal+ cells were also CD11b+ in young and old mice 7- and 14 days following injury, suggesting they are infiltrating immune cells. By 14 days, SA β-Gal+/CD11b+ cells from old mice expressed senescence genes, whereas those from young mice expressed higher levels of genes characteristic of anti-inflammatory macrophages. SA β-Gal+ cells remained elevated in old compared to young mice 28 days following injury, which were reduced by D+Q only in the old mice. In D+Q-treated old mice, muscle regenerated following injury to a greater extent compared to vehicle-treated old mice, having larger fiber cross-sectional area after 28 days. Conversely, D+Q blunted regeneration in young mice. In vitro experiments suggested D+Q directly improve myogenic progenitor cell proliferation. Enhanced physical function and improved muscle regeneration demonstrate that senolytics have beneficial effects only in old mice

Mobile Criminals, Immobile Crime: The Efficiency of Decentralized Crime Deterrence

In this paper we examine a class of local crimes that involve perfectly mobile criminals, and perfectly immobile criminal opportunities. We focus on local non-rival crime deterrence that is more efficient against criminals pursuing domestic crimes than criminals pursuing crimes elsewhere. In a standard case of sincerely delegated politicians and zero transfers to other districts, we show that centralized deterrence unambiguously dominates the decentralized deterrence. With strategic delegation and voluntary in-kind transfers, the tradeoff is exactly the opposite: Decentralization achieves the social optimum, whereas cooperative centralization overprovides for enforcement. This is robust to various cost-sharing modes. We also examine the effects of the growing interdependence of districts, stemming from criminals' increasing opportunities to strategically displace. Contrary to the supposition in Oates's decentralization theorem, increasing interdependence makes centralization less desirable

Clustering gene expression data with a penalized graph-based metric

<p>Abstract</p> <p>Background</p> <p>The search for cluster structure in microarray datasets is a base problem for the so-called "-omic sciences". A difficult problem in clustering is how to handle data with a manifold structure, i.e. data that is not shaped in the form of compact clouds of points, forming arbitrary shapes or paths embedded in a high-dimensional space, as could be the case of some gene expression datasets.</p> <p>Results</p> <p>In this work we introduce the Penalized k-Nearest-Neighbor-Graph (PKNNG) based metric, a new tool for evaluating distances in such cases. The new metric can be used in combination with most clustering algorithms. The PKNNG metric is based on a two-step procedure: first it constructs the k-Nearest-Neighbor-Graph of the dataset of interest using a low k-value and then it adds edges with a highly penalized weight for connecting the subgraphs produced by the first step. We discuss several possible schemes for connecting the different sub-graphs as well as penalization functions. We show clustering results on several public gene expression datasets and simulated artificial problems to evaluate the behavior of the new metric.</p> <p>Conclusions</p> <p>In all cases the PKNNG metric shows promising clustering results. The use of the PKNNG metric can improve the performance of commonly used pairwise-distance based clustering methods, to the level of more advanced algorithms. A great advantage of the new procedure is that researchers do not need to learn a new method, they can simply compute distances with the PKNNG metric and then, for example, use hierarchical clustering to produce an accurate and highly interpretable dendrogram of their high-dimensional data.</p

Elicitation of Neutralizing Antibodies Directed against CD4-Induced Epitope(s) Using a CD4 Mimetic Cross-Linked to a HIV-1 Envelope Glycoprotein

The identification of HIV-1 envelope glycoprotein (Env) structures that can generate broadly neutralizing antibodies (BNAbs) is pivotal to the development of a successful vaccine against HIV-1 aimed at eliciting effective humoral immune responses. To that end, the production of novel Env structure(s) that might induce BNAbs by presentation of conserved epitopes, which are otherwise occluded, is critical. Here, we focus on a structure that stabilizes Env in a conformation representative of its primary (CD4) receptor-bound state, thereby exposing highly conserved “CD4 induced” (CD4i) epitope(s) known to be important for co-receptor binding and subsequent virus infection. A CD4-mimetic miniprotein, miniCD4 (M64U1-SH), was produced and covalently complexed to recombinant, trimeric gp140 envelope glycoprotein (gp140) using site-specific disulfide linkages. The resulting gp140-miniCD4 (gp140-S-S-M64U1) complex was recognized by CD4i antibodies and the HIV-1 co-receptor, CCR5. The gp140-miniCD4 complex elicited the highest titers of CD4i binding antibodies as well as enhanced neutralizing antibodies against Tier 1 viruses as compared to gp140 protein alone following immunization of rabbits. Neutralization against HIV-27312/V434M and additional serum mapping confirm the specific elicitation of antibodies directed to the CD4i epitope(s). These results demonstrate the utility of structure-based approach in improving immunogenic response against specific region, such as the CD4i epitope(s) here, and its potential role in vaccine application