Growth Response from Herbicide, Prescribed Fire and Fertilizer Treatments in Midrotational Loblolly Pine: First-Year Results

This study was initiated to determine growth response resulting from the application of prescribed fire and herbicide, with and without fertilizatio.n. In. southeast Texas, herbicide, prescribed fire and fertilizer treatments were applied in m1d:rotat1onal loblolly pine plantations 1.5 years after thinning. Five replications were established at. each of two study sites located on similar soils, aspects and slopes. Half of each replication. was randomly selected and fertilized. Eight treatment plots were established 1n e~ch replication with one of each of the four treatments of control, herbicide, fire, and herb1c1de/flre randomly applied to fertilized plots and one of each of the four treatments randomly applied to non-fertilized plots. Pre-treatment measurements were taken in a 0.04 ha measurement plot nested within each treatment plot. A late season herbicide treatment of. lmazapyr and Arsenal was applied in October 1999. Burning was conducted in early spring of 2000 followed by fertilizer applications of diammonium phosphate and urea. ~osHreatment measurements were taken in December 2000. Growth response and s1gnif1cant treatment differences are presented in this paper

Pacific Northwest National Laboratory Site Environmental Report for Calendar Year 2011

The PNNL Site Environmental Report for Calendar Year 2011 was prepared pursuant to the requirements of Department of Energy (DOE) Order 231.1B, "Environment, Safety and Health Reporting" to provide a synopsis of calendar year 2011 information related to environmental management performance and compliance efforts. It summarizes site compliance with federal, state, and local environmental laws, regulations, policies, directives, permits, and orders and environmental management performance

Trajectory outlier detection: Algorithms, taxonomies, evaluation, and open challenges

acceptedVersio

Detection of Epidemic Scarlet Fever Group A Streptococcus in Australia.

Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing scarlet fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 scarlet fever isolate related to United Kingdom outbreak strains. National surveillance to monitor this pandemic is recommended

Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates.

UNLABELLED: We compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protein and a Gag-Pol-Nef polyprotein as Gag-induced virus-like particles (VLPs) (referred to as NYVAC-C and ALVAC-C). The immunization protocol consisted of two doses of the corresponding poxvirus vector plus two doses of a combination of the poxvirus vector and a purified HIV-1 gp120 protein from clade C. This immunogenicity profile was also compared to that elicited by vaccine regimens consisting of two doses of the ALVAC vector expressing HIV-1 antigens from clades B/E (ALVAC-vCP1521) plus two doses of a combination of ALVAC-vCP1521 and HIV-1 gp120 protein from clades B/E (similar to the RV144 trial regimen) or clade C. The results showed that immunization of macaques with NYVAC-C stimulated at different times more potent HIV-1-specific CD4(+) T-cell responses and induced a trend toward higher-magnitude HIV-1-specific CD8(+) T-cell immune responses than did ALVAC-C. Furthermore, NYVAC-C induced a trend toward higher levels of binding IgG antibodies against clade C HIV-1 gp140, gp120, or murine leukemia virus (MuLV) gp70-scaffolded V1/V2 and toward best cross-clade-binding IgG responses against HIV-1 gp140 from clades A, B, and group M consensus, than did ALVAC-C. Of the linear binding IgG responses, most were directed against the V3 loop in all immunization groups. Additionally, NYVAC-C and ALVAC-C also induced similar levels of HIV-1-neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) responses. Interestingly, binding IgA antibody levels against HIV-1 gp120 or MuLV gp70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVAC versus ALVAC expressing HIV-1 antigens in nonhuman primates and indicate that NYVAC may represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine. IMPORTANCE: The finding of a safe and effective HIV/AIDS vaccine immunogen is one of the main research priorities. Here, we generated two poxvirus-based HIV vaccine candidates (NYVAC and ALVAC vectors) expressing the same clade C HIV-1 antigens in separate vectors, and we analyzed in nonhuman primates their immunogenicity profiles. The results showed that immunization with NYVAC-C induced a trend toward higher HIV-1-specific cellular and humoral immune responses than did ALVAC-C, indicating that this new NYVAC vector could be a novel optimized HIV/AIDS vaccine candidate for human clinical trials.This investigation was supported by the PTVDC/CAVD program with support from the Bill and Melinda Gates Foundation (BMGF). Humoral immune monitoring data was supported by the BMGF CAVIMC 1032144 grant and the NIH/NIAID Duke Center for AIDS Research (CFAR) 5P30 AI064518. Novartis Vaccines received support for this work under contract number HHSN266200500007C from DAIDS-NIAID-NIH.This is the accepted manuscript. The final version is available at http://jvi.asm.org/content/early/2015/05/29/JVI.01265-15.abstract

Predicting outcomes in rheumatoid arthritis related interstitial lung disease

Aims: To compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RA-ILD) to identify patients with a progressive fibrosis phenotype.Methods: RAILD patients had CTs scored visually and by CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques: 1.Scleroderma system evaluating visual ILD extent and FVC values; 2.Fleischer Society IPF diagnostic guidelines applied to RAILD; 3.CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.Results: On univariable Cox analysis, all three staging systems strongly predicted outcome: Scleroderma System:HR=3.78, p=9×10-5; Fleischner System:HR=1.98, p=2×10-3; 4.4% VRS threshold:HR=3.10, p=4×10-4 When the Scleroderma and Fleischner Systems were combined, termed the Progressive Fibrotic System (C-statistic=0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF.On multivariable analysis, with adjustment for patient age, gender and smoking status, when analysed alongside the Progressive Fibrotic System, the VRS threshold of 4.4% independently predicted outcome (Model C-statistic=0.77).Conclusions: The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent

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

Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

Scalable Purification and Characterization of the Anticancer Lunasin Peptide from Soybean

Lunasin is a peptide derived from the soybean 2S albumin seed protein that has both anticancer and anti-inflammatory activities. Large-scale animal studies and human clinical trials to determine the efficacy of lunasin in vivo have been hampered by the cost of synthetic lunasin and the lack of a method for obtaining gram quantities of highly purified lunasin from plant sources. The goal of this study was to develop a large-scale method to generate highly purified lunasin from defatted soy flour. A scalable method was developed that utilizes the sequential application of anion-exchange chromatography, ultrafiltration, and reversed-phase chromatography. This method generates lunasin preparations of >99% purity with a yield of 442 mg/kg defatted soy flour. Mass spectrometry of the purified lunasin revealed that the peptide is 44 amino acids in length and represents the original published sequence of lunasin with an additional C-terminal asparagine residue. Histone-binding assays demonstrated that the biological activity of the purified lunasin was similar to that of synthetic lunasin. This study provides a robust method for purifying commercial-scale quantities of biologically-active lunasin and clearly identifies the predominant form of lunasin in soy flour. This method will greatly facilitate the development of lunasin as a potential nutraceutical or therapeutic anticancer agent