1,105 research outputs found
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Understanding Climate Change And Impacts On Tourism In The Outer Banks Of North Carolina
Local existence for the non-resistive MHD equations in nearly optimal Sobolev spaces
This paper establishes the local-in-time existence and uniqueness of solutions to the viscous, non-resistive magnetohydrodynamics (MHD) equations in RdRd , where d = 2, 3, with initial data B0∈Hs(Rd)B0∈Hs(Rd) and u0∈Hs−1+ϵ(Rd)u0∈Hs−1+ϵ(Rd) for s>d/2s>d/2 and any 0<ϵ<10<ϵ<1 . The proof relies on maximal regularity estimates for the Stokes equation. The obstruction to taking ϵ=0ϵ=0 is explained by the failure of solutions of the heat equation with initial data u0∈Hs−1u0∈Hs−1 to satisfy u∈L1(0,T;Hs+1)u∈L1(0,T;Hs+1) ; we provide an explicit example of this phenomenon
Rad51 and BRCA2 - New Molecular Targets for Sensitizing Glioma Cells to Alkylating Anticancer Drugs
First line chemotherapeutics for brain tumors (malignant gliomas) are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O6-alkylguanine, which is converted into DNA double-strand breaks (DSBs) that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ) is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA) approach targeting Rad51 and BRCA2, and for NHEJ we employed the DNA-PK inhibitor NU7026. We also assessed whether inhibition of poly(ADP)ribosyltransferase (PARP) by olaparib would enhance the killing effect. The data show that knockdown of Rad51 or BRCA2 greatly sensitizes cells to DSBs and the induction of cell death following temozolomide and nimustine (ACNU). It did not sensitize to ionizing radiation (IR). The expression of O6-methylguanine-DNA methyltransferase (MGMT) abolished all these effects, indicating that O6-alkylguanine induced by these drugs is the primary lesion responsible for the formation of DSBs and increased sensitivity of glioma cells following knockdown of Rad51 and BRCA2. Inhibition of DNA-PK only slightly sensitized to temozolomide whereas a significant effect was observed with IR. A triple strategy including siRNA and the PARP inhibitor olaparib further improved the killing effect of temozolomide. The data provides evidence that down-regulation of Rad51 or BRCA2 is a reasonable strategy for sensitizing glioma cells to killing by O6-alkylating anti-cancer drugs. The data also provide proof of principle that a triple strategy involving down-regulation of HR, PARP inhibition and MGMT depletion may greatly enhance the therapeutic effect of temozolomide
Local existence for the non-resistive MHD equations in Besov spaces
In this paper we prove the existence of solutions to the viscous, non-resistive magnetohydrodynamics (MHD) equations on the whole of Rn, n = 2, 3, for divergence-free initial data in certain Besov spaces, namely u0 ∈ Bn/2−1 2,1 and B0 ∈ Bn/2 2,1. The a priori estimates include the term t 0 u(s) 2 Hn/2 ds on the right-hand side, which thus requires an auxiliary bound in Hn/2−1. In 2D, this is simply achieved using the standard energy inequality; but in 3D an auxiliary estimate in H1/2 is required, which we prove using the splitting method of Calderón (1990) [2]. By contrast, our proof that such solutions are unique only applies to the 3D case
Expression of Escherichia coli F-18 Type 1 Fimbriae in the Streptomycin-Treated Mouse Large Intestine
Escherichia coli F-18, isolated from the feces of a healthy human, makes type 1 fimbriae and is an excellent colonizer of the streptomycin-treated mouse large intestine. Recently, it was shown that the inability to produce type 1 fimbriae had no effect on the ability of E. coli F-18 to colonize the streptomycin-treated mouse large intestine, suggesting the possibility that E. coli F-18 does not express type 1 fimbriae in vivo. However, we show here that E. coli F-18 does express type 1 fimbriae in mouse cecal mucus in vivo and, in fact, appears to express substantially more type 1 fimbriae in cecal mucus in vivo than in L broth in vitro
The zebrafish xenograft platform-A novel tool for modeling KSHV-associated diseases
Kaposi\u27s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic, but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the firs
Higher order commutator estimates and local existence for the non-resistive MHD equations and related models
This paper establishes the local-in-time existence and uniqueness of strong solutions in Hs for s > n/2 to the viscous, non-resistive magnetohydrodynamics (MHD) equations in Rn, n = 2, 3, as well as for a related model where the advection terms are removed from the velocity equation. The uniform bounds required for proving existence are established by means of a new estimate, which is a partial generalisation of the commutator estimate of Kato & Ponce (Comm. Pure Appl. Math. 41(7), 891–907, 1988)
Multigrid elliptic equation solver with adaptive mesh refinement
In this paper we describe in detail the computational algorithm used by our
parallel multigrid elliptic equation solver with adaptive mesh refinement. Our
code uses truncation error estimates to adaptively refine the grid as part of
the solution process. The presentation includes a discussion of the orders of
accuracy that we use for prolongation and restriction operators to ensure
second order accurate results and to minimize computational work. Code tests
are presented that confirm the overall second order accuracy and demonstrate
the savings in computational resources provided by adaptive mesh refinement.Comment: 12 pages, 9 figures, Modified in response to reviewer suggestions,
added figure, added references. Accepted for publication in J. Comp. Phy
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Multi-monoubiquitylation controls VASP-mediated actin dynamics Icon for The Forest of Biologists
The actin cytoskeleton performs multiple cellular functions, and as such, actin polymerization must be tightly regulated. We previously demonstrated that reversible, non-degradative ubiquitylation regulates the function of the actin polymerase VASP in developing neurons. However, the underlying mechanism of how ubiquitylation impacts VASP activity was unknown. Here, we show that mimicking multi-monoubiquitylation of VASP at K240 and K286 negatively regulates VASP interactions with actin. Using in vitro biochemical assays, we demonstrate the reduced ability of multi-monoubiquitylated VASP to bind, bundle, and elongate actin filaments. However, multi-monoubiquitylated VASP maintained the ability to bind and protect barbed ends from capping protein. Finally, we demonstrate the electroporation of recombinant multi-monoubiquitylated VASP protein altered cell spreading morphology. Collectively, these results suggest a mechanism in which ubiquitylation controls VASP-mediated actin dynamics
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