Development of radiosynthesis methods for 18F-labelled radiopharmaceuticals : General considerations and production of a dopamine transporter radioligand

Positron emission tomography (PET) is a molecular imaging technique that utilises radiopharmaceuticals (radiotracers) labelled with a positron-emitting radionuclide, such as fluorine-18 (18F). Development of a new radiotracer requires an appropriate radiosynthesis method: the most common of which with 18F is nucleophilic substitution with [18F]fluoride ion. The success of the labelling reaction is dependent on various factors such as the reactivity of [18F]fluoride, the structure of the target compound in addition to the chosen solvent. The overall radiosynthesis procedure must be optimised in terms of radiochemical yield and quality of the final product. Therefore, both quantitative and qualitative radioanalytical methods are essential in developing radiosynthesis methods. Furthermore, biological properties of the tracer candidate need to be evaluated by various pre-clinical studies in animal models. In this work, the feasibility of various nucleophilic 18F-fluorination strategies were studied and a labelling method for a novel radiotracer, N-3-[18F]fluoropropyl-2beta-carbomethoxy-3beta-4-fluorophenyl)nortropane ([18F]beta-CFT-FP), was optimised. The effect of solvent was studied by labelling a series of model compounds, 4-(R1-methyl)benzyl R2-benzoates. 18F-Fluorination reactions were carried out both in polar aprotic and protic solvents (tertiary alcohols). Assessment of the 18F-fluorinated products was studied by mass spectrometry (MS) in addition to conventional radiochromatographic methods, using radiosynthesis of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) as a model reaction. Labelling of [18F]beta-CFT-FP was studied using two 18F-fluoroalkylation reagents, [18F]fluoropropyl bromide and [18F]fluoropropyl tosylate, as well as by direct 18F-fluorination of sulfonate ester precursor. Subsequently, the suitability of [18F]beta-CFT-FP for imaging dopamine transporter (DAT) was evaluated by determining its biodistribution in rats. The results showed that protic solvents can be useful co-solvents in aliphatic 18F-fluorinations, especially in the labelling of sulfonate esters. Aromatic 18F-fluorination was not promoted in tert-alcohols. Sensitivity of the ion trap MS was sufficient for the qualitative analysis of the 18F-labelled products; p-[18F]MPPF was identified from the isolated product fraction with a mass-to-charge (m/z) ratio of 435 (i.e. protonated molecule [M+H]+). [18F]beta-CFT-FP was produced most efficiently via [18F]fluoropropyl tosylate, leading to sufficient radiochemical yield and specific radioactivity for PET studies. The ex vivo studies in rats showed fast kinetics as well as the specific uptake of [18F]beta-CFT-FP to the DAT rich brain regions. Thus, it was concluded that [18F]beta-CFT-FP has potential as a radiotracer for imaging DAT by PET.

On measurement of top polarization as a probe of t(t)over-bar production mechanisms at the LHC

In this note we demonstrate the use of top polarization in the study of t (t) over bar resonances at the LHC, in the possible case where the dynamics implies a non-zero top polarization. As a probe of top polarization we construct an asymmetry in the decay-lepton azimuthal angle distribution (corresponding to the sign of cos phi(l)) in the laboratory. The asymmetry is non-vanishing even for a symmetric collider like the LHC, where a positive z axis is not uniquely defined. The angular distribution of the leptons has the advantage of being a faithful top-spin analyzer, unaffected by possible anomalous tbW couplings, to linear order. We study, for purposes of demonstration, the case of a Z' as might exist in the little Higgs models. We identify kinematic cuts which ensure that our asymmetry reflects the polarization in sign and magnitude. We investigate possibilities at the LHC with two energy options: root s = 14TeV and root s = 7TeV, as well as at the Tevatron. At the LHC the model predicts net top quark polarization of the order of a few per cent for M-Z' similar or equal to 1200GeV, being as high as 10% for a smaller mass of the Z' of 700GeV and for the largest allowed coupling in the model, the values being higher for the 7TeV option. These polarizations translate to a deviation from the standard-model value of azimuthal asymmetry of up to about 4% (7%) for 14 (7) TeV LHC, whereas for the Tevatron, values as high as 12% are attained. For the 14TeV LHC with an integrated luminosity of 10 fb(-1), these numbers translate into a 3 sigma sensitivity over a large part of the range 500 less than or similar to M-Z' less than or similar to 1500GeV.

Microfinance, Efficiency and Agricultural Production in Bangladesh

The objectives of this study were to make a detailed and systematic empirical analysis of microfinance borrowers and non-borrowers in Bangladesh and also examine how efficiency measures are influenced by the access to agricultural microfinance. In the empirical analysis, this study used both parametric and non-parametric frontier approaches to investigate differences in efficiency estimates between microfinance borrowers and non-borrowers. This thesis, based on five articles, applied data obtained from a survey of 360 farm households from north-central and north-western regions in Bangladesh. The methods used in this investigation involve stochastic frontier (SFA) and data envelopment analysis (DEA) in addition to sample selectivity and limited dependent variable models. In article I, technical efficiency (TE) estimation and identification of its determinants were performed by applying an extended Cobb-Douglas stochastic frontier production function. The results show that farm households had a mean TE of 83% with lower TE scores for the non-borrowers of agricultural microfinance. Addressing institutional policies regarding the consolidation of individual plots into farm units, ensuring access to microfinance, extension education for the farmers with longer farming experience are suggested to improve the TE of the farmers. In article II, the objective was to assess the effects of access to microfinance on household production and cost efficiency (CE) and to determine the efficiency differences between the microfinance participating and non-participating farms. In addition, a non-discretionary DEA model was applied to capture directly the influence of microfinance on farm households production and CE. The results suggested that under both pooled DEA models and non-discretionary DEA models, farmers with access to microfinance were significantly more efficient than their non-borrowing counterparts. Results also revealed that land fragmentation, family size, household wealth, on farm-training and off farm income share are the main determinants of inefficiency after effectively correcting for sample selection bias. In article III, the TE of traditional variety (TV) and high-yielding-variety (HYV) rice producers were estimated in addition to investigating the determinants of adoption rate of HYV rice. Furthermore, the role of TE as a potential determinant to explain the differences of adoption rate of HYV rice among the farmers was assessed. The results indicated that in spite of its much higher yield potential, HYV rice production was associated with lower TE and had a greater variability in yield. It was also found that TE had a significant positive influence on the adoption rates of HYV rice. In article IV, we estimated profit efficiency (PE) and profit-loss between microfinance borrowers and non-borrowers by a sample selection framework, which provided a general framework for testing and taking into account the sample selection in the stochastic (profit) frontier function analysis. After effectively correcting for selectivity bias, the mean PE of the microfinance borrowers and non-borrowers were estimated at 68% and 52% respectively. This suggested that a considerable share of profits were lost due to profit inefficiencies in rice production. The results also demonstrated that access to microfinance contributes significantly to increasing PE and reducing profit-loss per hectare land. In article V, the effects of credit constraints on TE, allocative efficiency (AE) and CE were assessed while adequately controlling for sample selection bias. The confidence intervals were determined by the bootstrap method for both samples. The results indicated that differences in average efficiency scores of credit constrained and unconstrained farms were not statistically significant although the average efficiencies tended to be higher in the group of unconstrained farms. After effectively correcting for selectivity bias, household experience, number of dependents, off-farm income, farm size, access to on farm training and yearly savings were found to be the main determinants of inefficiencies. In general, the results of the study revealed the existence substantial technical, allocative, economic inefficiencies and also considerable profit inefficiencies. The results of the study suggested the need to streamline agricultural microfinance by the microfinance institutions (MFIs), donor agencies and government at all tiers. Moreover, formulating policies that ensure greater access to agricultural microfinance to the smallholder farmers on a sustainable basis in the study areas to enhance productivity and efficiency has been recommended. Key Words: Technical, allocative, economic efficiency, DEA, Non-discretionary DEA, selection bias, bootstrapping, microfinance, Bangladesh.

Harvesting undelimbed Scots pine (Pinus sylvestris L.) from first thinnings for integrated production of kraft pulp and energy

The present study evaluates the feasibility of undelimbed Scots pine (Pinus sylvestris L.) for integrated production of pulp and energy in a kraft pulp mill from the technical, economic and environmental points of view, focusing on the potential of bundle harvesting. The feasibility of tree sections for pulp production was tested by conducting an industrial wood-handling experiment, laboratory cooking and bleaching trials, using conventional small-diameter Scots pine pulpwood as a reference. These trials showed that undelimbed Scots pine sections can be processed in favourable conditions as a blend with conventional small-diameter pulpwood without reducing the pulp quality. However, fibre losses at various phases of the process may increase when using undelimbed material. In the economic evaluation, both pulp production and wood procurement costs were considered, using the relative wood paying capability of a kraft pulp mill as a determinant. The calculations were made for three Scots pine first-thinning stands with the breast-height diameter of the removal (6 12 cm) as the main distinctive factor. The supply chains included in the comparison were based on cut-to-length harvesting, whole-tree harvesting and bundle harvesting (whole-tree bundling). With the current ratio of pulp and energy prices, the wood paying capability declines with an increase in the proportion of the energy fraction of the raw material. The supply system based on the cut-to-length method was the most efficient option, resulting in the highest residual value at stump in most cases. A decline in the pulp price and an increase in the energy price improved the competitiveness of the whole-tree systems. With short truck transportation distances and low pulp prices, however, the harvesting of loose whole trees can result in higher residual value at stump in small-diameter stands. While savings in transportation costs did not compensate for the high cutting and compaction costs by the second prototype of the bundle harvester, an increase in transportation distances improved its competitiveness. Since harvesting undelimbed assortments increases nutrient export from the site, which can affect soil productivity, the whole-tree alternatives included in the present study cannot be recommended on infertile peatlands and mineral soils. The harvesting of loose whole trees or bundled whole trees implies a reduction in protective logging residues and an increase in site traffic or payloads. These factors increase the risk of soil damage, especially on peat soils with poor bearing capacity. Within the wood procurement parameters which were examined, the CO2 emissions of the supply systems varied from 13 27 kg m3. Compaction of whole trees into bundles reduced emissions from transportation by 30 39%, but these reductions were insufficient to compensate for the increased emissions from cutting and compaction.

Effect of 80 kDa protein of porcine follicular fluid on gonadotropin stimulated progesterone production in rat granulosa cells in vitro

We reported the presence of a 80 kDa polypeptide in porcine follicular fluid that inhibited the binding of 125I-radiolabelled hFSH as well as hCG to the rat ovarian gonadotropin receptors. In the present study, the biological activity of the receptor binding inhibitor is determined using an in vitro bioassay procedure. Granulosa cells isolated from PMSG primed immature rat ovaries respond to exogenously added gonadotropins in terms of progesterone production. Addition of fractions containing the gonadotropin receptor binding inhibitory activity inhibited progesterone production stimulated by the gonadotropins in a dose-dependent fashion. The receptor binding inhibitory activity was also capable of inhibiting progesterone production stimulated by PMSG, which has both FSH- and LH-like activities in rats. In contrast, progesterone production stimulated by dbcAMP was not inhibited by the receptor binding inhibitor. This result indicates that the site of action of the inhibitor is proximal to the formation of the cAMP. The above observations point out to a possible role for this factor in modulating gonadotropin activity at the ovarian level.

Citrate gel processing of the perovskite lanthanide chromites

Chemically pure and stoichiometric lanthanide chromites, LnCrO3, where Ln = La, Pr, Nd, Sm, Gd, Dy, Ho, Yb, Lu and YCrO3 have been prepared by the calcination of the corresponding lanthanide bis(citrato)chromium {Ln[Cr(C6H5O7)2·nH2O} complexes at relatively low temperatures. Formation of the chromites was confirmed by powder X-ray diffraction, infrared and electronic spectra. The citrate gel process is found to be highly economical, time-saving and appropriate for the large-scale production of these ceramic materials at low temperatures compared with other non-conventional methods.

Enhancement of Surface Flashover Performance of High Voltage Ceramic Disc Insulators

In this paper, an effort is made to study accurately the field distribution for various types of ceramic insulators used for high-voltage transmission. The surface charge simulation method (SCSM) is employed for the field computation. With the help of SCSM program, a Novel field reduction electrode is designed and developed to reduce the maximum field around the pin region. In order to experimentally analyze the performance of discs with field reduction electrode, special artificial pollution test facility was built and utilized. The experimental results show better surface flashover performance of ceramic insulators used in high-voltage transmission and distribution systems.

Production of Carcinogenic Acetaldehyde by Oral Microbiome

Oral cancer is the seventh most common cancer worldwide and its incidence is increasing. The most important risk factors for oral cancer are chronic alcohol consumption and tobacco smoking, up to 80 % of oral carcinomas are estimated to be caused by alcohol and tobacco. They both trigger an increased level of salivary acetaldehyde, during and after consumption, which is believed to lead to carcinogenesis. Acetaldehyde has multiple mutagenic features and it has recently been classified as a Group 1 carcinogen for humans by the International Agency for Research on Cancer. Acetaldehyde is metabolized from ethanol by microbes of oral microbiota. Some oral microbes possess alcohol dehydrogenase enzyme (ADH) activity, which is the main enzyme in acetaldehyde production. Many microbes are also capable of acetaldehyde production via alcohol fermentation from glucose. However, metabolism of ethanol into acetaldehyde leads to production of high levels of this carcinogen. Acetaldehyde is found in saliva during and after alcohol consumption. In fact, rather low ethanol concentrations (2-20mM) derived from blood to saliva are enough for microbial acetaldehyde production. The high acetaldehyde levels in saliva after alcohol challenge are explained by the lack of oral microbiota and mucosa to detoxify acetaldehyde by metabolizing it into acetate and acetyl coenzymeA. The aim of this thesis project was to specify the role of oral microbes in the in vitro production of acetaldehyde in the presence of ethanol. In addition, it was sought to establish whether microbial metabolism could also produce acetaldehyde from glucose. Furthermore, the potential of xylitol to inhibit ethanol metabolism and acetaldehyde production was explored. Isolates of oral microbes were used in the first three studies. Acetaldehyde production was analyzed after ethanol, glucose and fructose incubation with gas chromatography measurement. In studies I and III, the ADH enzyme activity of some microbes was measured by fluorescence. The effect of xylitol was analyzed by incubating microbes with ethanol and xylitol. The fourth study was made ex vivo and microbial samples obtained from different patient groups were analyzed. This work has demonstrated that isolates of oral microbiota are able to produce acetaldehyde in the presence of clinically relevant ethanol and glucose concentrations. Significant differences were found between microbial species and isolates from different patient groups. In particular, the ability of candidal isolates from APECED patients to produce significantly more acetaldehyde in glucose incubation compared to healthy and cancer patient isolates is an interesting observation. Moreover, xylitol was found to reduce their acetaldehyde production significantly. Significant ADH enzyme activity was found in the analyzed high acetaldehyde producing streptococci and candida isolates. In addition, xylitol was found to reduce the ADH enzyme activity of C. albicans. Some results from the ex vivo study were controversial, since acetaldehyde production did not correlate as expected with the amount of microbes in the samples. Nevertheless, the samples isolated from patients did produce significant amounts of acetaldehyde with a clinically relevant ethanol concentration.

Reduction behaviour of Fe3+/Al2O3 obtained from the mixed oxalate precursor and the formation of the Fe0-Al2O3 metal-ceramic composite

Reduction behaviour of Fe3+/Al2O3 obtained by the decomposition of the oxalate precursor has been investigated by employing X-ray diffraction (XRD), Mössbauer spectroscopy and electron paramagnetic resonance (EPR) spectroscopy. Calcination of Fe3+/Al2O3 at or below 1070 K yields mainly a poorly ordered, fine particulate form of ?-Al2�xFexO3. Calcination at or above 1220 K yields ?-Al2�xFexO3. Reduction of Fe3+/Al2O3 samples calcined at or below 1070 K gives the FeAl2O4 spinel on reduction at 870 K; samples calcined at or above 1220 K give Al2-xFexO3 with a very small proportion of metallic iron. Fe3+/Al2O3 samples calcined at 1220 K or above yield metallic iron and a very small proportion of the spinel on reduction below 1270 K. In the samples reduced at or above 1270 K, the main product is metallic iron in both ferromagnetic and superparamagnetic forms. The oxalate precursor route yields more metallic iron than the sol�gel route.

Supermacroporous Polymer-Based Cryogel Bioreactor for Monoclonal Antibody Production in Continuous Culture Using Hybridoma Cells

Cryogel matrices composed of different polymeric blends were synthesized, yielding a unique combination of hydrophilicity and hydrophobicity with the presence or absence of charged surface. Four such cryogel matrices composed of polyacrylamide-chitosan (PAAC), poly(N-isopropylacrylamide)-chitosan, polyacrylonitrile (PAN), and poly(N-isopropylacrylamide) were tested for growth of different hybridoma cell lines and production of antibody in static culture. All the matrices were capable for the adherence of hybridoma cell lines 6A4D7, B7B10, and H9E10 to the polymeric surfaces as well as for the efficient monoclonal antibody (mAb) production. PAAC proved to be relatively better in terms of both mAb production and cell growth. Further, PAAC cryogel was designed into three different formats, monolith, disks, and beads, and used as packing material for packed-bed bioreactor. Longterm cultivation of 6A4D7 cell line on PAAC cryogel scaffold in all the three formats could be successfully done for a period of 6 weeks under static conditions. Continuous packed-bed bioreactor was setup using 6A4D7 hybridoma cell line in the three reactor formats. The reactors ran continuously for a period of 60 days during which mAb production and metabolism of cells in the bioreactors were monitored periodically. The monolith bioreactor performed most efficiently over a period of 60 days and produced a total of 57.5 mg of antibody in the first 30 days (in 500 mL) with a highest concentration of 115 mu g mL(-1), which is fourfold higher than t-flask culture. The results demonstrate that appropriate chemistry and geometry of the bioreactor matrix for cell growth and immobilization can enhance the reactor productivity. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 27: 170-180, 2011

Large negative magnetoresistance and metal-insulator transition observed in MnO/C composite coatings grown on ceramic alumina by metalorganic chemical vapor deposition

MnO/C composite coatings were grown by the metalorganic chemical vapor deposition process on ceramic alumina in argon ambient. Characterization by various techniques confirms that these coatings are homogeneous composites comprising nanometer-sized MnO particles embedded in a matrix of nanometer-sized graphite. Components of the MnO/C composite coating crystalline disordered, but are electrically quite conductive. Resistance vs. temperature measurements show that coating resistance increases exponentially from a few hundred ohms at room temperature to a few megaohms at 30 K. Logarithmic plots of reduced activation energy vs. temperature show that the coating material undergoes a metal-insulator transition. The reduced activation energy exponent for the film under zero magnetic field was 2.1, which is unusually high, implying that conduction is suppressed at much faster rate than the Mott or the Efros-Shklovskii hopping mechanism. Magnetoconductance us. magnetic field plots obtained at various temperatures show a high magnetoconductance (similar to 28.8%) at 100 K, which is unusually large for a disordered system, wherein magnetoresistance is attributed typically to weak localization. A plausible explanation for the unusual behavior observed in the carbonaceous disordered composite material is proposed. (C) 2010 Elsevier Ltd. All rights reserved.

Investigations on the Corona performance of a Ceramic disc Insulators integrated with Field Reduction Electrode

This paper presents laboratory investigations on the visible corona and discharge radio noise. Experimental investigations are carried on various types of normal and anti-fog types of ceramic disc insulator at the recently established artificial pollution experimental facility. The results obtained from the experimental investigations show better performance for the disc insulators fitted with field reduction electrodes. In addition to the corona and radio noise investigations the comparisons are also made for the experimental results of the potential distribution across the insulator string (with and without filed reduction electrode) with the simulation results obtained by using Surface Charge Simulation Method.

Dynamics of I-asterisk(P-2(1/2)) production inthe ultraviolet photodissociation of alkyn iodides

The relative quantum yields, phi*, for the production of I*(P-2(1/2)) at 266, 280, and similar to 305 nm are reported for a series of primary alkyl iodides using the technique of two-photon laser-induced fluorescence for the detection of I(P-2(3/2)) and I*(P-2(1/2)) atoms. Results are analyzed by invoking the impulsive energy disposal model, which summarizes the dynamics of dissociation as a single parameter. Comparison of our data with those calculated by a more sophisticated time-dependent quantum mechanical model is also made. Near the red edge of the alkyl iodide A band, absorption contribution from the (3)Q(1) state is important and the dynamics near the (3)Q(0)-(1)Q(1) curve-crossing region seem to be influenced by the kinematics of the dissociation process

Fe-Cr/Al2O3 metal-ceramic composites: Nature and size of the metal particles formed during hydrogen reduction

Fe-Cr/Al2O3 metal-ceramic composites prepared by hydrogen reduction at different temperatures and for different periods have been investigated by a combined use of Mossbauer spectroscopy, x-ray diffraction, transmission electron microscopy, and energy-dispersive x-ray spectroscopy in order to obtain information on the nature of the metallic species formed. Total reduction of Fe3+ does not occur by increasing the reduction time at 1320 K from 1 to 30 h, and the amount of superparamagnetic metallic species is essentially constant (about 10%). Temperatures higher than 1470 K are needed to achieve nearly total reduction of substitutional Fe3+. Interestingly, iron favors the reduction of chromium. The composition of the Fe-Cr particles is strongly dependent on their size, the Cr content being higher in particles smaller than 10 nm.