Comparison of H/Al stoichiometry of mineral and organic soils in Brazil

Exchangeable Al has been used as a criterion for the calculation of lime requirement in several Brazilian States. However, the laboratory method with extraction by a 1 mol L-1 KCl solution followed by indirect alkaline titration is not accurate for some Brazilian soils, mainly in the case of soils with high organic matter content. The objective of this study was therefore to evaluate the stoichiometry of H+/Al3+ in KCl soil extracts. The results suggested that organically complexed Al is the main contributor to exchangeable acidity in soils enriched with organic matter. Liming recommendations for organic soils based exclusively on exchangeable Al determined by the NaOH titration method should therefore be revised.

Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury.

BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. OBJECTIVE: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. METHODS AND RESULTS: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Expression analyses of three members of the AtPHO1 family reveal differential interactions between signaling pathways involved in phosphate deficiency and the responses to auxin, cytokinin, and abscisic acid.

The PHO1 protein is involved in loading inorganic phosphate (Pi) to the root xylem. Ten genes homologous to AtPHO1 are present in the Arabidopsis thaliana (L.) Heyn genome. From this gene family, transcript levels of only AtPHO1, AtPHO1;H1 and AtPHO1;H10 were increased by Pi-deficiency. While the up-regulation of AtPHO1;H1 and AtPHO1;H10 by Pi deficiency followed the same rapid kinetics and was dependent on the PHR1 transcription factor, phosphite only strongly suppressed the expression of AtPHO1;H1 and had a minor effect on AtPHO1;H10. Addition of sucrose was found to increase transcript levels of both AtPHO1 and AtPHO1;H1 in Pi-sufficient or Pi-deficient plants, but to suppress AtPHO1:H10 under the same conditions. Treatments of plants with auxin or cytokinin had contrasting effect depending on the gene and on the Pi status of the plants. Thus, while both hormones down-regulated expression of AtPHO1 independently of the plant Pi status, auxin and cytokinin up-regulated AtPHO1;H1 and AtPHO1;H10 expression in Pi-sufficient plants and down-regulated expression in Pi-deficient plants. Treatments with abscisic acid inhibited AtPHO1 and AtPHO1;H1 expression in both Pi-sufficient and Pi-deficient plants, but increased AtPHO1;H10 expression under the same conditions. The inhibition of expression by abscisic acid of AtPHO1 and AtPHO1;H1, and of the Pi-starvation responsive genes AtPHT1;1 and AtIPS1, was dependant on the ABI1 type 2C protein phosphatase. These results reveal that various levels of cross talk between the signal transduction pathways to Pi, sucrose and phytohormones are involved in the regulation of expression of the three AtPHO1 homologues.

Antibody-dependent cell-mediated cytolysis of human colon carcinoma cells induced by specific antisera against carcinoembryonic antigen.

Antibody-dependent lymphocyte cytotoxicity against human colon carcinoma cells grown in vitro was demonstrated with rabbit anti-carcinoembryonic antigen (CEA) antisera and normal human lymphocytes. The same antisera produced no tumor cell lysis in a complement-dependent cytotoxicity test. The specificity of the reaction was demonstrated by the inhibition of antibody-dependent lymphocyte cytotoxicity after the addition of increasing amounts of purified CEA to the antiserum and by the fact that only tumor cell lines expressing CEA on their surface were lysed. Antibody-dependent lymphocyte cytotoxicity was also observed against two colon carcinoma cell lines that expressed Blood Group A antigen, using a human serum containing anti-Blood Group A antibodies of the immunoglobulin G class. This reaction was specifically inhibited by absorption with Blood Group A red cells, whereas the anti-CEA-dependent cytotoxicity was not inhibited by absorption with red cells of different blood groups.

Aggregation of subtropical soil under liming: a study using laser diffraction

Laser diffraction (LD) provides detailed analysis of particle size distribution. Its application to testing the stability of soil aggregates can assist studies on the aggregation of soils with contrasting electrochemical properties. The objectives of the present work were: (a) to propose a protocol for using LD to study soil aggregation, (b) to study the aggregation of an Acrisol under the influence of different doses and forms of lime. Samples were collected in 2005 from a Brazilian Acrisol that in 1994 had received 0.0; 2.0; 8.5 and 17.0 Mg ha-1 of lime, left on the soil surface or incorporated. Aggregates from 4.76 to 8.00 mm diameters were studied using the traditional method proposed by Kemper & Chepil (1965), with wet sieving, while aggregates from 1.00 to 2.00 mm were studied using a CILAS® laser diffractometer that distinguishes particles ranging from 0.04 to 2,500.00 μm. LD readings were made after six consecutive pre-treatments, using agitation times, a chemical dispersion agent and ultrasound. Mean Weighted Diameter (MWD) and the Aggregate Stability Index (ASI) calculated, using the traditional method does not discriminate the treatments. However, LD is able to produce detailed data on soil aggregation, resulting in indexes of stability of aggregates that are linearly related to the doses of lime applied (MWD: R² = 0.986 and ASI: R² = 0.876). It may be concluded that electrochemical changes in the Brazilian Acrisol resulting from incorporated lime affect the stability of aggregates, increasing stability with increased doses of lime.

An EORTC phase I itudy of bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.

Rice grown in nutrient solution with doses of manganese and silicon

Although silicon is not recognized as a nutrient, it may benefit rice plants and may alleviate the Mn toxicity in some plant species. The dry matter yield (root, leaf, sheaths and leaf blade) and plant architecture (angle of leaf insertion and leaf arc) were evaluated in rice plants grown in nutrient solutions with three Mn doses, with and without Si addition. The treatments were arranged in a 2 x 3 factorial [with and without (2 mmol L-1) Si; three Mn doses (0.5; 2.5 and 10 µmol L-1)], in a randomized block design with 4 replications. The experimental unit was a 4 L plastic vase with 4 rice (Metica-1 cultivar) plants. Thirty nine days after keeping the seedlings in the nutrient solution the plant dry matter yield was determined; the angle of leaf insertion in the sheath and the leaf arc were measured; and the Si and Mn concentrations in roots, sheaths and leaves were determined. The analysis of variance (F test at 5 and 1 % levels) and the regression analysis (for testing plant response to Mn with the Si treatments) were performed. The Si added to the nutrient solution increased the dry matter yield of roots, sheaths and leaf blades and also decreased the angle of leaf blade insertion into the sheath and the foliar arc in the rice plant. Additionally, it ameliorated the rice plant architecture which allowed an increase in the dry matter yield. Similarly, the addition of Mn to the solution improved the architecture of the rice plants with gain in dry matter yield. As Si was added to the nutrient solution, the concentration of Mn in leaves decreased and in roots increased thus alleviating the toxic effects of Mn on the plants.

A regulatory network for the efficient control of transgene expression.

BACKGROUND: Expression of heterologous genes in mammalian cells or organisms for therapeutic or experimental purposes often requires tight control of transgene expression. Specifically, the following criteria should be met: no background gene activity in the off-state, high gene expression in the on-state, regulated expression over an extended period, and multiple switching between on- and off-states. METHODS: Here, we describe a genetic switch system for controlled transgene transcription using chimeric repressor and activator proteins functioning in a novel regulatory network. In the off-state, the target transgene is actively silenced by a chimeric protein consisting of multimerized eukaryotic transcriptional repression domains fused to the DNA-binding tetracycline repressor. In the on-state, the inducer drug doxycycline affects both the derepression of the target gene promoter and activation by the GAL4-VP16 transactivator, which in turn is under the control of an autoregulatory feedback loop. RESULTS: The hallmark of this new system is the efficient transgene silencing in the off-state, as demonstrated by the tightly controlled expression of the highly cytotoxic diphtheria toxin A gene. Addition of the inducer drug allows robust activation of transgene expression. In stably transfected cells, this control is still observed after months of repeated cycling between the repressed and activated states of the target genes. CONCLUSIONS: This system permits tight long-term regulation when stably introduced into cell lines. The underlying principles of this network system should have general applications in biotechnology and gene therapy.

Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3.

We have analyzed the presentation of human histocompatability leukocyte antigen-A*0201-associated tumor peptide antigen MAGE-3271-279 by melanoma cells. We show that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a minigene encoding the preprocessed fragment MAGE-3271-279 failed to recognize cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides extended at the NH2 or COOH terminus of MAGE-3271-279 with purified human proteasome revealed that the generation of the COOH terminus of the antigenic peptide was impaired. Surprisingly, addition of lactacystin to purified proteasome, though partially inhibitory, resulted in the generation of the antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271-279-specific CTL. We therefore postulate that the generation of antigenic peptides by the proteasome in cells can be modulated by the selective inhibition of certain of its enzymaticactivities.

Atomic parity nonconservation, neutron radii, and effective field theories of nuclei

Accurately calibrated effective field theories are used to compute atomic parity nonconserving (APNC) observables. Although accurately calibrated, these effective field theories predict a large spread in the neutron skin of heavy nuclei. Whereas the neutron skin is strongly correlated to numerous physical observables, in this contribution we focus on its impact on new physics through APNC observables. The addition of an isoscalar-isovector coupling constant to the effective Lagrangian generates a wide range of values for the neutron skin of heavy nuclei without compromising the success of the model in reproducing well-constrained nuclear observables. Earlier studies have suggested that the use of isotopic ratios of APNC observables may eliminate their sensitivity to atomic structure. This leaves nuclear structure uncertainties as the main impediment for identifying physics beyond the standard model. We establish that uncertainties in the neutron skin of heavy nuclei are at present too large to measure isotopic ratios to better than the 0.1% accuracy required to test the standard model. However, we argue that such uncertainties will be significantly reduced by the upcoming measurement of the neutron radius in 208^Pb at the Jefferson Laboratory.

Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.

Slow Dynamics of Ising Models with Energy Barriers

Using Monte Carlo simulations we study the dynamics of three-dimensional Ising models with nearest-, next-nearest-, and four-spin (plaquette) interactions. During coarsening, such models develop growing energy barriers, which leads to very slow dynamics at low temperature. As already reported, the model with only the plaquette interaction exhibits some of the features characteristic of ordinary glasses: strong metastability of the supercooled liquid, a weak increase of the characteristic length under cooling, stretched-exponential relaxation, and aging. The addition of two-spin interactions, in general, destroys such behavior: the liquid phase loses metastability and the slow-dynamics regime terminates well below the melting transition, which is presumably related with a certain corner-rounding transition. However, for a particular choice of interaction constants, when the ground state is strongly degenerate, our simulations suggest that the slow-dynamics regime extends up to the melting transition. The analysis of these models leads us to the conjecture that in the four-spin Ising model domain walls lose their tension at the glassy transition and that they are basically tensionless in the glassy phase.

Optimization of the sampling scheme for maps of physical and chemical properties estimated by kriging

The sampling scheme is essential in the investigation of the spatial variability of soil properties in Soil Science studies. The high costs of sampling schemes optimized with additional sampling points for each physical and chemical soil property, prevent their use in precision agriculture. The purpose of this study was to obtain an optimal sampling scheme for physical and chemical property sets and investigate its effect on the quality of soil sampling. Soil was sampled on a 42-ha area, with 206 geo-referenced points arranged in a regular grid spaced 50 m from each other, in a depth range of 0.00-0.20 m. In order to obtain an optimal sampling scheme for every physical and chemical property, a sample grid, a medium-scale variogram and the extended Spatial Simulated Annealing (SSA) method were used to minimize kriging variance. The optimization procedure was validated by constructing maps of relative improvement comparing the sample configuration before and after the process. A greater concentration of recommended points in specific areas (NW-SE direction) was observed, which also reflects a greater estimate variance at these locations. The addition of optimal samples, for specific regions, increased the accuracy up to 2 % for chemical and 1 % for physical properties. The use of a sample grid and medium-scale variogram, as previous information for the conception of additional sampling schemes, was very promising to determine the locations of these additional points for all physical and chemical soil properties, enhancing the accuracy of kriging estimates of the physical-chemical properties.