Evolution of the Hemifused Intermediate on the Pathway to Membrane Fusion

AbstractThe pathway to membrane fusion in synthetic and biological systems is thought to pass through hemifusion, in which the outer leaflets are fused while the inner leaflets engage in a hemifusion diaphragm (HD). Fusion has been proposed to be completed by lysis of the expanded HD that matures from a localized stalklike initial connection. However, the process that establishes the expanded HD is poorly understood. Here we mathematically modeled hemifusion of synthetic vesicles, where hemifusion and fusion are most commonly driven by calcium and membrane tension. The model shows that evolution of the hemifused state is driven by these agents and resisted by interleaflet frictional and tensile stresses. Predicted HD growth rates depend on tension and salt concentration, and agree quantitatively with experimental measurements. For typical conditions, we predict that HDs expand at ∼30 μm2/s, reaching a final equilibrium area ∼7% of the vesicle area. Key model outputs are the evolving HD tension and area during the growth transient, properties that may determine whether HD lysis occurs. Applying the model to numerous published experimental studies that reported fusion, our results are consistent with a final fusion step in which the HD ruptures due to super-lysis HD membrane tensions

Phishing Intelligence Using the Simple Set Comparison Tool

Phishing websites, phish, attempt to deceive users into exposing their passwords, user IDs, and other sensitive information by imitating legitimate websites, such as banks, product vendors, and service providers. Phishing investigators need fast automated tools to analyze the volume of phishing attacks seen today. In this paper, we present the Simple Set Comparison tool. The Simple Set Comparison tool is a fast automated tool that groups phish by imitated brand allowing phishing investigators to quickly identify and focus on phish targeting a particular brand. The Simple Set Comparison tool is evaluated against a traditional clustering algorithm over a month\u27s worth of phishing data, 19,825 confirmed phish. The results show clusters of comparable quality, but created more than 37 times faster than the traditional clustering algorithm. Keywords: phishing, phish kits, phishing investigation, data mining, parallel processin

Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine

AbstractIntestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.</jats:p

Analysis of Ticonderoga Class Cruiser operating targets for other consumables, repair parts, and administrative expenditures

MBA Professional ReportThe purpose of this project is to analyze Ticonderoga Class Cruiser Operating Targets (OPTAR) for the Atlantic Fleet (LANTFLT) and the Pacific Fleet (PACFLT). The scope of the analysis focused on the Ticonderoga Class Cruisers - the surface combatants with the least amount of configuration differences among the class. This project was conducted with the sponsorship and assistance of Commander Naval Surface Forces (CNSF). The goal of this project is to provide CNSF with underlying causes which explain lower expenditures for LANTFLT than PACFLT in the sub accounts of Other Consumable (SO), Repair (SR), and Administrative (SX). Due to levels of data available and the proportion of total expenditures that each sub-account represented, the emphasis of the analysis was concentrated on the Other Consumable and the Repair Parts Sub-accounts. The project developed a methodology to analyze expenditures within the cruiser class by three different levels; the sub-account level, the expense element level, and the system level. The cruisers were classified into groups based on their fleet, homeport, area classification (OCONUS or CONUS), and baseline configuration, at the sub-account and expense element level to see if there were relationships within the different groupings.http://archive.org/details/analysisofticond1094510344Approved for public release; distribution is unlimited

Applying Corn Condensed Distillers Solubles to Hay Windrows Prior to Baling: I. Procedure and Effects on Bale Temperature and Nutrient Composition

Two experiments investigated the effects of applying liquid corn condensed distillers solubles to grass-hay windrows prior to baling on storage, bale temperature, and nutrient composition. Application of the wet material did not impair the ability of hay to expel heat post-baling in either study. Increased CP and decreased NDF for hay treated with corn condensed distillers solubles indicated successful within-bale storage occurred. Results suggest application prior to baling is a feasible strategy for storing liquid co-products while improving forage quality

Short-Term Calorie Restriction in Male Mice Feminizes Gene Expression and Alters Key Regulators of Conserved Aging Regulatory Pathways

Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown, and the involvement of the TOR and sirtuin pathways (which regulate aging in simpler organisms) remain controversial. Additionally, females of most mammals appear to live longer than males within species; and, although it remains unclear whether this holds true for mice, the relationship between sex-biased and CR-induced gene expression remains largely unexplored. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the sirtuin pathway. Using western analysis we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of females

2003 Philip C. Jessup International Law Moot Court Competition International Court Of Justice At The Peace Palace The Hague, Netherlands

The Republic of Annolay and the Republic of Reston have submitted the present dispute by Special Agreement to the International Court of Justice pursuant to Articles 36(1) and 40(1) of the Statute of the Court for final resolution

Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation

Human immunodeficiency virus (HIV) can infect resting CD4 T cells residing in lymphoid tissues but not those circulating in peripheral blood. The molecular mechanisms producing this difference remain unknown. We explored the potential role of the tissue microenvironment and its influence on the action of the antiviral factor APOBEC3G (A3G) in regulating permissivity to HIV infection. We found that endogenous IL-2 and -15 play a key role in rendering resident naive CD4 T cells susceptible to HIV infection. Infection of memory CD4 T cells also requires endogenous soluble factors, but not IL-2 or -15. A3G is found in a high molecular mass complex in HIV infection–permissive, tissue-resident naive CD4 T cells but resides in a low molecular mass form in nonpermissive, blood-derived naive CD4 T cells. Upon treatment with endogenous soluble factors, these cells become permissive for HIV infection, as low molecular mass A3G is induced to assemble into high molecular mass complexes. These findings suggest that in lymphoid tissues, endogenous soluble factors, likely including IL-2 and -15 and others, stimulate the formation of high molecular mass A3G complexes in tissue-resident naive CD4 T cells, thereby relieving the potent postentry restriction block for HIV infection conferred by low molecular mass A3G

Room-temperature exciton-polaritons with two-dimensional WS2

Two-dimensional transition metal dichalcogenides exhibit strong optical transitions with significant potential for optoelectronic devices. In particular they are suited for cavity quantum electrodynamics in which strong coupling leads to polariton formation as a root to realisation of inversionless lasing, polariton condensationand superfluidity. Demonstrations of such strongly correlated phenomena to date have often relied on cryogenic temperatures, high excitation densities and were frequently impaired by strong material disorder. At room-temperature, experiments approaching the strong coupling regime with transition metal dichalcogenides have been reported, but well resolved exciton-polaritons have yet to be achieved. Here we report a study of monolayer WS$_2$ coupled to an open Fabry-Perot cavity at room-temperature, in which polariton eigenstates are unambiguously displayed. In-situ tunability of the cavity length results in a maximal Rabi splitting of $\hbar \Omega_{\rm{Rabi}} = 70$ meV, exceeding the exciton linewidth. Our data are well described by a transfer matrix model appropriate for the large linewidth regime. This work provides a platform towards observing strongly correlated polariton phenomena in compact photonic devices for ambient temperature applications.Comment: 12 pages, 6 figure