Performance of Standardized Relative CBV for Quantifying Regional Histologic Tumor Burden in Recurrent High-Grade Glioma: Comparison against Normalized Relative CBV Using Image-Localized Stereotactic Biopsies.

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%-100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%-100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor. CONCLUSIONS: Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.

Metal absorption properties of Mentha spicata grown under tannery sludge amended soil-its effect on antioxidant system and oil quality.

Tannery sludge (TS) is hazardous to environment and its disposal in an ecofriendly manner is a major challenge. An experiment was conducted to investigate the metal absorption properties of Mentha spicata grown under different levels of TS amended soil (soil: sludge in 100:0, 75:25, 50:50, 25:75 and 0:100 ratio) and its effect on the antioxidant system and oil quality. At 75:25 ratio of sludge and soil, metal translocation factor was ≥0.5 for Cr, Cd, and Co and for Ni and for Pb ≥ 1. Carvone, limonene, dihydrocarvone and other oil constituents along with biomass were maximum in 75:25 ratio of sludge and soil. Superoxide dismutase (SOD), CAT (Catalases), POD (Peroxidases), MDA (Malondialdehyde) and proline play a major role in detoxification of reactive oxygen species generated due to TS (heavy metal stress). Antioxidant (SOD, CAT and POD), MDA and proline showed an increasing trend as the concentration of TS increased with the treatments. To test the relationship between 23 character principal component analysis (PCA) was performed. PC-I contributed 56% of total variance while PC-II contributed 37% of total variance. The results concluded that M. spicata performed well in terms of oil yield and multiple metal translocations in 75:25 sludge and soil ratio.

Performance of rose scented geranium (Pelargonium graveolens) in heavy metal polluted soil vis-à-vis phytoaccumulation of metals.

An investigation was carried out to evaluate the effect of heavy metal toxicity on growth, herb, oil yield and quality and metal accumulation in rose scented geranium (Pelargonium graveolens) grown in heavy metal enriched soils. Four heavy metals (Cd, Ni, Cr, and Pb) each at two levels (10 and 20 mg kg-1 soil) were tested on geranium. Results indicated that Cr concentration in soil at 20 mg kg-1 reduced leaves, stem and root yield by 70, 83, and 45%, respectively, over control. Root growth was significantly affected in Cr stressed soil. Nickel, Cr, and Cd concentration and accumulation in plant increased with higher application of these metals. Chromium, nickel and cadmium uptake was observed to be higher in leaves than in stem and roots. Essential oil constituents were generally not significantly affected by heavy metals except Pb at 10 and 20 ppm, which significantly increased the content of citronellol and Ni at 20 ppm increased the content of geraniol. Looking in to the higher accumulation of toxic metals by geranium and the minimal impact of heavy metals on quality of essential oil, geranium can be commercially cultivated in heavy metal polluted soil for production of high value essential oil.

Impairment of soil health due to fly ash-fugitive dust deposition from coal-fired thermal power plants.

Thermal power stations apart from being source of energy supply are causing soil pollution leading to its degradation in fertility and contamination. Fine particle and trace element emissions from energy production in coal-fired thermal power plants are associated with significant adverse effects on human, animal, and soil health. Contamination of soil with cadmium, nickel, copper, lead, arsenic, chromium, and zinc can be a primary route of human exposure to these potentially toxic elements. The environmental evaluation of surrounding soil of thermal power plants in Odisha may serve a model study to get the insight into hazards they are causing. The study investigates the impact of fly ash-fugitive dust (FAFD) deposition from coal-fired thermal power plant emissions on soil properties including trace element concentration, pH, and soil enzymatic activities. Higher FAFD deposition was found in the close proximity of power plants, which led to high pH and greater accumulation of heavy metals. Among the three power plants, in the vicinity of NALCO, higher concentrations of soil organic carbon and nitrogen was observed whereas, higher phosphorus content was recorded in the proximity of NTPC. Multivariate statistical analysis of different variables and their association indicated that FAFD deposition and soil properties were influenced by the source of emissions and distance from source of emission. Pollution in soil profiles and high risk areas were detected and visualized using surface maps based on Kriging interpolation. The concentrations of chromium and arsenic were higher in the soil where FAFD deposition was more. Observance of relatively high concentration of heavy metals like cadmium, lead, nickel, and arsenic and a low concentration of enzymatic activity in proximity to the emission source indicated a possible link with anthropogenic emissions.

Palmarosa [Cymbopogon martinii (Roxb.) Wats.] as a putative crop for phytoremediation, in tannery sludge polluted soil.

A field experiment using tannery sludge as a soil amendment material and palmarosa (Cymbopogon martinii) as a potential phytostabilizer was conducted to investigate their synergistic effect in relation to the improvement in soil quality/property. Three consecutive harvests of two cultivars of palmarosa-PRC-1 and Trishna, were examined to find out the influence of different tannery sludge doses on their herb, dry matter, essential oil yield and heavy metal accumulation. Soil fertility parameters (N, P, K, Organic carbon) were markedly affected by different doses of sludge. Enhanced soil nitrogen was positively correlated with herb yield (0.719*) and plant height (0.797*). The highest dose of tannery sludge (100 t ha(-1)) exhibited best performance than other treatments with respect to herb, dry matter and oil yield in all three harvests. Trishna was found to be superior to PRC-1 in relation to same studied traits. Quality of oil varied, but was insignificant statistically. Uptake of heavy metals followed same order (Cr>Ni>Pb>Cd) in roots and shoots. Translocation factor <1 for all trace elements and Bioconcentration factor >1 was observed in case of all heavy metals. Overall, tannery sludge enhanced the productivity of crop and metal accumulation occurred in roots with a meager translocation to shoots, hence it can be used as a phytostabiliser. The major advantage of taking palmarosa in metal polluted soil is that unlike food and agricultural crops, the product (essential oil) is extracted by hydro-distillation and there is no chance of oil contamination, thus is commercially acceptable.

Application of Heavy Metal Rich Tannery Sludge on Sustainable Growth, Yield and Metal Accumulation by Clarysage (Salvia sclarea L.).

A field experiment was conducted to evaluate the effective utilization of tannery sludge for cultivation of clarysage (Salvia sclarea) at CIMAP research farm, Lucknow, India during the year 2012-2013. Six doses (0, 20, 40, 60, 80, 100 tha(-1)) of processed tannery sludge were tested in randomised block design with four replications. Results revealed that maximum shoot, root, dry matter and oil yield were obtained with application of 80 tha(-1)of tannery sludge and these were 94, 113 and 61% higher respectively, over control. Accumulation of heavy metals (Cr, Ni, Fe, Pb) were relatively high in shoot portion of the plant than root. Among heavy metals, magnitude of chromium accumulation was higher than nickel, iron and lead in shoot as well as in root. Linalool, linalyl acetate and sclareol content in oil increased by 13,8 and 27% respectively over control, with tannery sludge application at 80 tha(-1). Heavy metals such as chromium, cadmium and lead content reduced in postharvest soil when compared to initial status. Results indicated that clarysage (Salvia sclarea) can be grown in soil amended with 80 tha(-1)sludge and this can be a suitable accumulator of heavy metals for phytoremediation of metal polluted soils.

Utilization of heavy metal-rich tannery sludge for sweet basil (Ocimum basilicum L.) cultivation.

Unlike food crops, essential oil-bearing crops in which the oil is extracted through hydro-distillation can be a suitable crop to be grown in heavy metal-polluted soils as the oil does not carry any heavy metal. In a field experiment conducted at CIMAP, Lucknow, India during 2011 and 2012, influence of six doses of tannery sludge viz 0, 10, 20, 30, 40, and 50 t ha(-1) were tested, taking sweet basil (Ocimum basilicum) as the test crop. Maximum herb yield was obtained with the application of sludge at 20 t ha(-1). While in root, accumulation of Cd and Pb increased significantly up to 20 t ha(-1), Cr accumulation increased with increasing the dose of tannery sludge reaching maximum at 50 t ha(-1). Essential oil yield of basil (Ocimum basilicum) was significantly affected due to sludge application. Quality of essential oil, in term of chemical constituents, however, was marginally influenced due to tannery sludge application.

HS-SPME-GC-FID method for detection and quantification of Bacillus cereus ATCC 10702 mediated 2-acetyl-1-pyrroline.

A rapid micro-scale solid-phase micro-extraction (SPME) procedure coupled with gas-chromatography with flame ionized detector (GC-FID) was used to extract parts per billion levels of a principle basmati aroma compound "2-acetyl-1-pyrroline" (2-AP) from bacterial samples. In present investigation, optimization parameters of bacterial incubation period, sample weight, pre-incubation time, adsorption time, and temperature, precursors and their concentrations has been studied. In the optimized conditions, detection of 2-AP produced by Bacillus cereus ATCC10702 using only 0.5 g of sample volume was 85 µg/kg. Along with 2-AP, 15 other compounds produced by B. cereus were also reported out of which 14 were reported for the first time consisting mainly of (E)-2-hexenal, pentadecanal, 4-hydroxy-2-butanone, n-hexanal, 2-6-nonadienal, 3-methoxy-2(5H) furanone and 2-acetyl-1-pyridine and octanal. High recovery of 2-AP (87 %) from very less amount of B. cereus samples was observed. The method is reproducible fast and can be used for detection of 2-AP production by B. cereus.

Influence of heavy metal rich tannery sludge on soil enzymes vis-à-vis growth of Tagetes minuta, an essential oil bearing crop.

Tannery sludge is available in plenty and is hazardous to environment as well as plant and animal life. It is very important to manage the tannery sludge in an environmentally sound manner. The aim of this study was to assess the physico-chemical, microbial and biochemical properties of soil treated with different levels of sludge. In this study, Tagetes minuta an essential oil bearing crop was grown in two different textured soils treated with different levels of tannery sludge. Application of tannery sludge (TS) increased the growth and oil yield of plant and also the activity of urease and soil microbial biomass nitrogen (SMBN) when applied in 50:50 combinations of soil:sludge. The crop performed well in coarse soil with a soil:sludge ratio of 50:50. High concentration of tannery sludge exhibited inhibitory effect on SMBN and urease activity. Acid/alkaline phosphatase, dehydrogenase and soil microbial biomass carbon (SMBC) increased as the sludge concentration increased in soil. This may be due to high organic matter present in tannery sludge. Roots accumulated more metal than the shoot. No detectable amount of metal was found in oil of T.minuta. To test the relation between 20 characters principal component analysis (PCA) was performed. PCA analysis indicates that cation exchange capacity (CEC), SMBC, dehydrogenase, acid and alkaline phosphatases were grouped in group 1. SMBN, urease and cis-ocimene content in oil were in group 2 whereas biomasss, chlorophyll a, limonene, Z and E-tagetone were in group 3. PC-I contributes 54% of total variance and PC-II contributes 38% of the total variance. The results concluded that T.minuta can mitigate metal toxicity by root absorption. Microbial activity and biomass of plant was higher in coarse soil with TS than fine soil with TS.

Organic C dynamics and its conservation under wheat (Triticum aesetivum) - mint (Mentha arvensis)-Sesbania rostrata cropping in sub-tropical condition of northern Indo-Gangetic plains.

Soil organic carbon (SOC) is accumulated or depleted as a result of cropping and management strategies. It plays a significant role in maintaining soil quality, plant productivity and mitigating greenhouse gas emission. We studied the long-term (20 years) influence of a wheat-mint-Sesbania cropping system on the SOC stock. Estimates of stabilization of SOC in different pools and a tentative C budget were also developed. Twenty years of cultivation caused a decrease in SOC only in control soils, which received no manure and fertilizer. However, it increased with balanced use of NPK inputs. Soil C stock decreased significantly with increased in soil depth 0-15 cm to 15-30 and 30-45 cm. About 6% (-2 to+14) of the C added in crop residues and green manure were stabilized in the soil. On an average 12%, 14%, 59%, 15% of the water stable aggregates were in the >2 mm, 2.0-0.25 mm, 0.25-0.05 mm, and <0-0.5 size fractions, respectively. Significant improvements in structural stability and nitrogen availability were detected in all the treatments compared to the control. The amount of organic C oxidizable by a modified Walkley and Black method, which involves using only half of the amount of sulphuric acid, is a more sensitive indicator of the improvement in soil quality parameters under investigation, namely SOC, and increases in mineralizable N and water stable aggregation than the standard method.

Effect of metal tolerant plant growth promoting bacteria on growth and metal accumulation in Zea mays plants grown in fly ash amended soil.

The present study was undertaken to examine the effect of the application of fly ash (FA) into Garden soil (GS), with and without inoculation of plant growth promoting bacteria (PGPB), on the growth and metal uptake by Zea mays plants. Three FA tolerant PGPB strains, Pseudomonas sp. PS5, PS14, and Bacillus sp. BC29 were isolated from FA contaminated soils and assessed for their plant growth promoting features on the Z. mays plants. All three strains were also examined for their ability to solubilize phosphate and to produce Indole Acetic Acid (IAA), siderophores, and hydrogencynide acid (HCN) production. Although inoculation of all strains significantly enhanced the growth of plants at both the concentration of FA but maximum growth was observed in plants inoculated with BC29 and PS14 at low level (25%) of FA concentration. The experimental results explored the plant growth promoting features of selected strains which not only enhanced growth and biomass of plants but also protected them from toxicity of FA.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 x 10(10) viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007.

Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1beta.

OBJECTIVE: To provide a more complete picture of the effect of interleukin-1 beta (IL-1beta) on adult human articular chondrocyte gene expression, in contrast to the candidate gene approach. DESIGN: Chondrocytes from human knee cartilage were cultured in medium containing IL-1beta. Changes in gene expression were analyzed by microarray and reverse transcriptase-polymerase chain reaction analysis. The ability of transforming growth factor beta-1 (TGF-beta1), fibroblast growth factor (FGF)-18, and bone morphogenetic protein 2 (BMP-2) to alter the effects of IL-1beta was analyzed. Computational analysis of the promoter regions of differentially expressed genes for transcription factor binding motifs was performed. RESULTS: IL-1beta-treated human chondrocytes showed significant increases in the expression of granulocyte colony stimulating factor-3, endothelial leukocyte adhesion molecule 1 and leukemia inhibitory factor as well as for a large group of chemokines that include CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CCL2, CCL3, CCL4, CCL5, CCL8, CCL20, CCL3L1, CX3CL1 and the cytokine IL-6. As expected, the mRNA for matrix metalloproteinase (MMP)-13 and BMP-2 also increased while mRNA for the matrix genes COL2A1 and aggrecan was down-regulated. A subset of chemokines increased rapidly at very low levels of IL-1beta. The phenotype induced by IL-1beta was partially reversed by TGF-beta1, but not by BMP-2. In the presence of IL-1beta, FGF-18 increased expression of ADAMTS-4, aggrecan, BMP-2, COL2A1, CCL3, CCL4, CCL20, CXCL1, CXCL3, CXCL6, IL-1beta, IL-6, and IL-8 and decreased ADAMTS-5, MMP-13, CCL2, and CCL8. Computational analysis revealed a high likelihood that the most up-regulated chemokines are regulated by the transcription factors myocyte enhancer binding factor-3 (MEF-3), CCAAT/enhancer binding protein (C/EBP) and nuclear factor-kappa B (NF-kappaB). CONCLUSION: IL-1beta has a diverse effect on gene expression profile in human chondrocytes affecting matrix genes as well as chemokines and cytokines. TGF-beta1 has the ability to antagonize some of the phenotype induced by IL-1beta.

Medicinal and aromatic plant materials as nitrification inhibitors for augmenting yield and nitrogen uptake of Japanese mint (Mentha arvensis L. Var. Piperascens).

Pot experiments were conducted to evaluate the relative performance of medicinal and aromatic plant materials and dicyandiamide (DCD) as nitrification inhibitors to regulate transformation of N from urea. Their effect on the efficiencies of use of N by Japanese mint (Mentha arvensis cv. Hy 77) was tested. Urea was coated with these materials viz., Mentha spicata, Artemisia annua or DCD at the rate of 5% (w/w) of fertilizer urea using an appropriate coating technique. Nimin (tetranortriterpenoids, an ethanol extract of neem (Azadirachta indica Juss) coating was done at the rate of 1% w/w of urea. Fertilizer nitrogen was applied at 100 and 200 mg kg(-1) soil. These natural coating materials significantly increased the herb and essential oil yields of the crop at both rates of fertilizer nitrogen compared to urea alone and were found to be as effective as DCD in retarding NO3- formation in soil. Herb yield increased by 6-81% when compared to uncoated urea. The increase in essential oil yield ranged between 3% and 68% due to coating. The effectiveness of the nitrification-inhibitor--coated urea, however, varied with the soils used and the rate of fertilizer nitrogen applied. The results suggest that the natural products could be potential nitrification inhibitors for increasing fertilizer N use efficiency.

Total synthesis of (+/-)-stemodinone via an efficient ring-exchange strategy.

A total synthesis of (+/-)-stemodinone, a tetracyclic stemodane diterpene, from the known tricyclic methyl olefin 11 is described. The key steps involve an efficient ring-exchange reaction and palladium(0)-catalyzed lactone migration. The ring-exchange strategy for controlling the stereochemistry was based on an initial Diels-Alder reaction to form a new ring followed by cleavage of the original ring. Cleavage of the original ring of the Diels-Alder adduct 9 was achieved by an initial regio- and chemoselective Baeyer-Villiger oxidation followed by the Pd(0)-catalyzed lactone-migration reaction reported by us.

Total synthesis of (+/-)-scopadulin.

The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.

The first total synthesis of (+/-)-scopadulin, an antiviral aphidicolane diterpene.

[reaction: see text] The first total synthesis of (+/-)-scopadulin was accomplished by a stereoselective construction of a quaternary carbon at C-4, conversion of the hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols, and a highly chemo- and stereoselective methylation at C-16.

Concentration dependent red shift: qualitative and quantitative investigation of motor oils by synchronous fluorescence scan.

Synchronous fluorescence scan (SFS) has been described as a successful technique to characterize Motor oils like diesel, petrol, kerosene, 2T oil and Mobil. The concentration dependent investigation of Motor oils shows a red shift in lambda(SFS)(max). Using red shift of lambda(SFS)(max), a method has been developed to quantify Motor oil in the concentration range 5-100% v/v. The concentration dependent overall rate of energy transfer of Motor oil gives a unique behavioral change according to the oil type and SFS is a simpler spectroscopic method to qualitatively differentiate between heavy and light oil. The molecular interaction of polycyclic aromatic compounds (PACs) in fluorophoric mixtures like resonance energy transfer and self-quenching via solvent collision has been clearly explained by SFS method. Effect of solvent and external quencher molecule on Motor oils has also been studied. Nitrobenzene is found to be a selective quencher for PACs of Motor oils.