Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA.

Long-term expression of coagulation factor IX (FIX) has been observed in murine and canine models following administration of recombinant adeno-associated viral (rAAV) vectors into either the portal vein or muscle. These studies were designed to evaluate factors that influence rAAV-mediated FIX expression. Stable and persistent human FIX (hFIX) expression (> 22 weeks) was observed from 4 vectors after injection into the portal circulation of immunodeficient mice. The level of expression was dependent on promoter with the highest expression, 10% of physiologic levels, observed with a vector containing the cytomegalovirus (CMV) enhancer/beta-actin promoter complex (CAGG). The kinetics of expression after injection of vector particles into muscle, tail vein, or portal vein were similar with hFIX detectable at 2 weeks and reaching a plateau by 8 weeks. For a given dose, intraportal administration of rAAV CAGG-FIX resulted in a 1.5-fold or 4-fold higher level of hFIX compared to tail vein or intramuscular injections, respectively. Polymerase chain reaction analysis demonstrated predominant localization of the rAAV FIX genome in liver and spleen after tail vein injection with a higher proportion in liver after portal vein injection. Therapeutic levels of hFIX were detected in the majority of immunocompetent mice (21 of 22) following intravenous administration of rAAV vector without the development of anti-hFIX antibodies, but hFIX was not detected in 14 immunocompetent mice following intramuscular administration, irrespective of strain. Instead, neutralizing anti-hFIX antibodies were detected in all the mice. These observations may have important implications for hemophilia B gene therapy with rAAV vectors

Author Correction: Fermiology and electron dynamics of trilayer nickelate La4Ni3O10.

The original version of this Article contained errors in Fig. 2, Fig. 3a-c and Supplementary Fig. 2. In Fig. 2g and Supplementary Fig. 2, the band structure plot calculated from density function theory (DFT) had a missing band of mainly z2 character that starts at about - 0.25 eV at the Y point and disperses downwards towards the Γ point. This band was inadvertently neglected when transferring the lines from the original band plot to the enhanced version for publication. Also in Fig. 2g, the points labelled M and Y were not exactly at (1/2 1/2 0) and (0 1/2 0), but rather (0.52 0.48 0) and (0 0.48 0) due to a bug in XCrysDen for low-symmetry structures that the authors failed to identify before publication. Thus, the bands presented were slightly off the true M-Y direction and additional splitting incorrectly appeared (in particular for the highly dispersive bands of x2-y2 character). The correct versions of Fig. 2g (cited as Fig. 1) and Supplementary Fig. 2 (cited as Fig. 2) are:which replaces the previous incorrect version, cited here as Fig. 3 and Fig. 4:Neither of these errors in Fig. 2g or Supplementary Fig. 2 affects either the discussion or any of the interpretations of the ARPES data provided in the paper. The authors discussed the multilayer band splitting along the Γ-M direction (δ band and α band as assigned in the paper), and ARPES did not see any split band. The authors did not discuss the further splitting that arises due to back folding along the M-Y direction.In Fig. 3a-c, the errors in the M and Y points in Fig. 2g cause subtle changes to the DFT dispersions. The correct version of Fig. 3a-c is cited here as Fig 5:which replaces the previous incorrect version (Fig. 6):However, the influence on the effective mass results of Fig. 3d is negligible.These errors have now been corrected in both the PDF and HTML versions of the Article. The authors acknowledge James Rondinelli and Danilo Puggioni from Northwestern University for calling our attention to these issues

Heterogeneous Os isotope compositions in the Kalatongke sulfide deposit, NW China: the role of crustal contamination

Re-Os isotope compositions of mantle-derived magmas are highly sensitive to crustal contamination because the crust and mantle have very different Os isotope compositions. Crustal contamination may trigger S saturation and thus the formation of magmatic Ni-Cu-(PGE) sulfide deposits. The ∼287-Ma Kalatongke norite intrusion of NW China are hosted in carboniferous tuffaceous rocks and contain both disseminated and massive sulfide mineralization. The Re-Os isotope compositions in the intrusion are highly variable. Norite and massive sulfide ores have γ Os values ranging from +59 to +160 and a Re-Os isochron age of 239 ± 51 Ma, whereas disseminated sulfide ores have γ Os values from +117 to +198 and a Re-Os isochron age of 349 ± 34 Ma. The variability of Os isotope compositions can be explained as the emplacement of two distinct magma pulses. Massive sulfide ores and barren norite in the intrusion formed from the same magma pulse, whereas the disseminated sulfide ores with more radiogenic Os isotopes formed from another magma pulse which underwent different degrees of crustal contamination. Re-Os isotopes may not be suitable for dating sulfide-bearing intrusions that underwent variable degrees of crustal contamination to form magmatic sulfide deposits. © 2012 The Author(s).published_or_final_versionSpringer Open Choice, 28 May 201

Large Scale Reasoning Using Allen's Interval Algebra

This paper proposes and evaluates a distributed, parallel approach for reasoning over large scale datasets using Allen's Interval Algebra (IA). We have developed and implemented algorithms that reason over IA networks using the Spark distributed processing framework. Experiments have been conducted by deploying the algorithms on computer clusters using synthetic datasets with various characteristics. We show that reasoning over datasets consisting of millions of interval relations is feasible and that our implementation scales effectively. The size of the IA networks we are able to reason over is far greater than those found in previously published works

Heterogeneous mantle source and magma differentiation of quaternary arc-like volcanic rocks from Tengchong, SE margin of the Tibetan Plateau

The Tengchong volcanic field north of the Burma arc comprises numerous Quaternary volcanoes in the southeastern margin of the Tibetan Plateau. The volcanic rocks are grouped into four units (1-4) from the oldest to youngest. Units 1, 3 and 4 are composed of olivine trachybasalt, basaltic trachyandesite and trachyandesite, and Unit 2 consists of hornblende dacite. The rocks of Units 1, 3, and 4 form a generally alkaline suite in which the rocks plot along generally linear trends on Harker diagrams with only slight offset from unit to unit. They contain olivine phenocrysts with Fo values ranging from 65 to 85 mol% and have Cr-spinel with Cr# ranging from 23 to 35. All the rocks have chondrite-normalized REE patterns enriched in LREE and primitive mantle-normalized trace element patterns depleted in Ti, Nb and Ta, but they are rich in Th, Ti and P relative to typical arc volcanics. Despite minor crustal contamination, 87Sr/ 86Sr ratios (0.706-0.709), εNd values (-3.2 to -8.7), and εHf values (+4.8 to -6.4) indicate a highly heterogeneous mantle source. The Pb isotopic ratios of the lavas ( 206Pb/ 204Pb = 18.02-18.30) clearly show an EMI-type mantle source. The underlying mantle source was previously modified by subduction of the Neo-Tethyan oceanic and Indian continental lithosphere. The present heterogeneous mantle source is interpreted to have formed by variable additions of fluids and sediments derived from the subducted Indian Oceanic lithosphere, probably the Ninety East Ridge. Magma generation and emplacement was facilitated by transtensional NS-trending strike-slip faulting. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 28 May 201

Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies

Objective. To study the pattern of protein expression associated with a predisposition to develop ovarian cancer. Methods. Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE). Results. Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction. Conclusions. Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk. © 2005 Elsevier Inc. All rights reserved.postprin

Developing a voltage-stability-constrained security assessment system part I: Determination of power system voltage security operation limits

The method for determining the voltage security operation limits in a practical voltage security analysis (VSA) system based on VSAT software for large power systems is introduced in this paper. These operation limits include bus voltage limits, branch/corridor transfer power limits and P-load limit of the whole system. The voltage security operation limits are determined by the most critical contingency among the studied contingency set. The most critical contingency determines the P-load limit of the whole system, and all kinds of operation parameter limits are operation parameter values corresponding to this P-load limit under pre-contingency. An operation parameter limit is upper limit if the function relationship between this operation parameter and load power is an increasing curve, or lower limit if the function relationship between this operation parameter and load power is an decreasing curve. These operation parameter limits are helpful for operators to monitor the system operation state. © 2005 IEEE.published_or_final_versio

Electromagnetic performances and main parameter sensitivity effect on unbalance magnetic flux in a New Single‑Phase FEFSM with segmental rotor

Three-phase field excitation flux switching motor (FEFSM) with salient rotor structure has been introduced with their advantages of rotor easy temperature elimination and controllable FEC magnetic flux. Yet, the salient rotor structure is found to lead a longer magnetic flux path between stator and rotor parts, producing a weak flux linkage along with low torque performances. Hence, a new structure of single-phase FEFSM using segmental rotor with non-overlap windings is proposed with advantages of shorter magnetic flux path, light weight and robust rotor structure. Analysis on fundamental magnetic flux characteristics, armature and FEC magnetic flux linkages, cogging torque, back-Emf, various torque capabilities, refinement of unbalance magnetic flux, and torque-power versus speed characteristics are conducted using 2D FEA through JMAG Designer version 15. The results show that magnetic flux amplitude ratio has been improved by 41.2% while the highest torque and power achieved are 1.45 Nm and 343.8 W, respectively

Developing a voltage-stability-constrained security assessment system part II : Structure and function design and technology used

This is the second part in a two-part paper on the development of a voltage stability constrained security assessment system (VSC-SAS). In this part, overall VSC-SAS structure and function design and technology used will be presented. The system is expected to be used in both on-line and off-line modes. In on-line mode, on-line SCADA/EMS data will be used for VSC-SAS use; while in off-line mode (usually day-ahead calculation), historical data can be used for VSC-SAS. Both results (i.e. system operation limits) can be selected to compare with real time operation conditions and supervision power system operation security margin. © 2005 IEEE.published_or_final_versio