Liu, G.
Zhang, Y.
Ni, Z.
Yun, T.
Sheng, Z.
Liang, H.
Hua, J.
Li, S.
Du, Q.
Chen, J.
We report the first full-length infectious clone of strain JX/CHA/97 of rabbit hemorrhagic disease virus (RHDV). The transcripts from the full-length cDNA clones were infectious when they were directly injected into rabbits. The sequence of the virus recovered from the rabbits was identical to that of the injected RNA transcripts. The cDNA clone was engineered to contain one silent nucleotide change to create an EcoRV site (A to T at nucleotide 2908). The genetic marker was retained in the recovered progeny virus. The transfection of RNA transcripts into RK-13 cells resulted in the synthesis of viral antigens, indicating that the cDNA clones were replication competent. This stable infectious molecular clone should be an important tool for developing a better understanding of the molecular biology and pathogenesis of RHDV.
Sorotsky, H.
Cabanero, M.
Moskovitz, M.
Weiss, J.
Pintilie, M.
Leighl, N.
Bradbury, P.
Liu, G.
Kia, A.
Pugh, T.
Torti, D.
Torchia, J.
Tsao, M.
Shepherd, F.
Liu, G.
Yarov-Yarovoy, V.
Nobbs, M.
Clare, J.J.
Scheuer, T.
Catterall, W.A.
Voltage-gated sodium channels are blocked by local anesthetic and anticonvulsant drugs. A receptor site for local anesthetics has been defined in transmembrane segment S6 in domain IV (IVS6) of the α subunit, but the anticonvulsant lamotrigine and related compounds have more complex structures than local anesthetics and may interact with additional amino acid residues. Apparent KD values for inactivated-state block of rat brain type IIA sodium channels expressed in Xenopus oocytes were 31.9 μM, 17.3 μM, 3.7 μM and 10.3 μM for lamotrigine and compounds 227c89, 4030w92 and 619c89, respectively. Compound 619c89 was the strongest frequency-dependent blocker, which correlated with higher affinity and a five-fold slower recovery from drug block compared to lamotrigine. Examination of lamotrigine block of mutant sodium channel α subunits, in which alanine had been substituted for each individual amino acid in IVS6, identified mutations I1760A, F1764A and Y1771A as causing the largest reductions in affinity (six-, seven- and 12-fold, respectively). The ratios of effects of these three mutations differed for compounds 227c89, 4030w92, and 619c89. The amino acid residues interacting with these pore-blocking drugs define a surface of IVS6 that is exposed to the pore and may rotate during gating.
One of the major benefits of attenuated phase-shifting masks, or half-tone masks, over binary masks is the increase in depth-of-focus. This improvement, however, is drastically reduced if phase error over the entire reticle is excessive. It is well known that phase error causes focal shift at the wafer level, leading to loss of useful depth of focus. Controlling phase error is therefore critical in achieving good lithographic performance with the embedded attenuated phase-shifting mask (EPSM). Recently, tools were developed that can be used to measure phase at 248 nm wavelength. However, these tools cannot measure the phase of actual device patterns such as 0.25 mum contact holes due to the beam size. This paper presents a new approach that directly measures the focal shift of actual device patterns using aerial image measurement. We have successfully utilized this approach in our development of EPSM reticle fabrication process leading to a focal shift uniformity of les0.2 mum over the entire 6" EPSM reticle. This new approach is also being used as a quality control tool in our mask fabrication process. The new metrology pattern design is described. Measurement accuracy and repeatability and the data analysis methodology are discussed
Greenhouse gas, especially CO2, emissions impact on global climate has been widely recognised. Emissions reduction has become an important issue. Efforts have been made globally in establishing emission policies and protocols. However, considering the fact that different countries have different carbon reduction schemes, and significant variations are still possible for existing schemas, future CO2 prices can be highly uncertain. The power generation sector will be significantly affected by changing policies and therefore significant uncertainties will be involved in the operation and investment processes. Moreover, investments in thermal power plants are also influenced by many other uncertain factors such as fuel prices, spot electricity prices and the investment behaviours of rival generation companies. An appropriate method is urgently needed to model these uncertainties in the investment process. A novel framework of generation investment decision-making is proposed herewith. The option game theory is employed to handle multiple uncertain factors. The investment decision making will be solved with a Barraquand-Martineau option pricing model-based method. Case studies are conducted to assess the performance of the proposed framework.
Social enterprise is a hybrid form of profit-and social benefit-seeking organization whereby traditional nonprofit organizations pursue both their social mission and business opportunities. To embrace this new strategic direction shift, the nonprofit organizations need to develop new competences that will enable them to respond to the changes in the business model. The article investigates the learning mechanisms through which social enterprises develop a marketing capability to deploy their resources in the marketplace as the drivers of competitive advantage in their commercial practice. We study eight cases of U.K.-based charity retailers to address the role of knowledge accumulation, articulation, and codification process in the evolution of marketing capability development. We identify, among other things, that the critical process of organizational learning for social enterprise is to transfer the experience into organization-specific knowledge under the social aspects of constraints.
Liu, G.
Jeraj, R.
Vanderhoek, M.
Perlman, S.
Kolesar, J.
Harrison, M.
Simoncic, U.
Eickhoff, J.
Carmichael, L.
Chao, B.
Marnocha, R.
Ivy, P.
Wilding, G.
Purpose: To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3'-deoxy-3'-[(18)F] fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging. Patients and Methods: Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg p.o. daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic (PK) data were assessed at the same time points. Results: Sixteen patients (8 patients on 4/2 schedule and 8 patients on 2/1 schedule) completed all three planned FLT PET/CT scans and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scans 2 to 3), median FLT PET standardized uptake value (SUV(mean)) increased +15% (range: -14% to 277%; P = 0.047) for the 4/2 schedule and +19% (range: -5.3% to 200%; P 0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure and returned toward baseline during the treatment withdrawal. Conclusions: The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI) withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early "angiogenic escape." Clin Cancer Res; 17(24); 7634-44. (C)2011 AACR.