A barrier and techno-economic analysis of small-scale bCHP (biomass combined heat and power) schemes in the UK

bCHP (Biomass combined heat and power) systems are highly efficient at smaller-scales when a significant proportion of the heat produced can be effectively utilised for hot water, space heating or industrial heating purposes. However, there are many barriers to project development and this has greatly inhibited deployment in the UK. Project viability is highly subjective to changes in policy, regulation, the finance market and the low cost fossil fuel incumbent. The paper reviews the barriers to small-scale bCHP project development in the UK along with a case study of a failed 1.5MWel bCHP scheme. The paper offers possible explanations for the project's failure and suggests adaptations to improve the project resilience. Analysis of the project's: capital structuring contract length and bankability; feedstock type and price uncertainty, and plant oversizing highlight the negative impact of the existing project barriers on project development. The research paper concludes with a discussion on the effects of these barriers on the case study project and this industry more generally. A greater understanding of the techno-economic effects of some barriers for small-scale bCHP schemes is demonstrated within this paper, along with some methods for improving the attractiveness and resilience of projects of this kind. © 2014 Elsevier Ltd.

Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier

Blood cholesterol levels are not consistently elevated in subjectswith age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased longterm risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life. © The Authors Journal compilation © 2014 Biochemical Society.

Laser-induced breakdown spectroscopy quantitative analysis method via adaptive analytical line selection and relevance vector machine regression model

Abstract A new LIBS quantitative analysis method based on analytical line adaptive selection and Relevance Vector Machine (RVM) regression model is proposed. First, a scheme of adaptively selecting analytical line is put forward in order to overcome the drawback of high dependency on a priori knowledge. The candidate analytical lines are automatically selected based on the built-in characteristics of spectral lines, such as spectral intensity, wavelength and width at half height. The analytical lines which will be used as input variables of regression model are determined adaptively according to the samples for both training and testing. Second, an LIBS quantitative analysis method based on RVM is presented. The intensities of analytical lines and the elemental concentrations of certified standard samples are used to train the RVM regression model. The predicted elemental concentration analysis results will be given with a form of confidence interval of probabilistic distribution, which is helpful for evaluating the uncertainness contained in the measured spectra. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples have been carried out. The multiple correlation coefficient of the prediction was up to 98.85%, and the average relative error of the prediction was 4.01%. The experiment results showed that the proposed LIBS quantitative analysis method achieved better prediction accuracy and better modeling robustness compared with the methods based on partial least squares regression, artificial neural network and standard support vector machine.

Phytoestrogens modulate breast cancer resistance protein expression and function at the blood-cerebrospinal fluid barrier

PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS: Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS: A 24 hour cytotoxicity assay (0.001 µM-1000 µM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 µM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre-incubation with modulators alone, a 0.16-2.5-fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-β-estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION: We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition.

A laser induced breakdown spectroscopy quantitative analysis method based on the robust least squares support vector machine regression model

Data fluctuation in multiple measurements of Laser Induced Breakdown Spectroscopy (LIBS) greatly affects the accuracy of quantitative analysis. A new LIBS quantitative analysis method based on the Robust Least Squares Support Vector Machine (RLS-SVM) regression model is proposed. The usual way to enhance the analysis accuracy is to improve the quality and consistency of the emission signal, such as by averaging the spectral signals or spectrum standardization over a number of laser shots. The proposed method focuses more on how to enhance the robustness of the quantitative analysis regression model. The proposed RLS-SVM regression model originates from the Weighted Least Squares Support Vector Machine (WLS-SVM) but has an improved segmented weighting function and residual error calculation according to the statistical distribution of measured spectral data. Through the improved segmented weighting function, the information on the spectral data in the normal distribution will be retained in the regression model while the information on the outliers will be restrained or removed. Copper elemental concentration analysis experiments of 16 certified standard brass samples were carried out. The average value of relative standard deviation obtained from the RLS-SVM model was 3.06% and the root mean square error was 1.537%. The experimental results showed that the proposed method achieved better prediction accuracy and better modeling robustness compared with the quantitative analysis methods based on Partial Least Squares (PLS) regression, standard Support Vector Machine (SVM) and WLS-SVM. It was also demonstrated that the improved weighting function had better comprehensive performance in model robustness and convergence speed, compared with the four known weighting functions.

On some Sufficient Conditions for High Breakdown Point of ML Estimators

High breakdown point estimators LME(k) and LT E(k) for location and scale are obtained for symmetrical exponentially decreasing density family.

Application of the D-Fullness Technique for Breakdown Point Study of the Trimmed Likelihood Estimator to a Generalized Logistic Model

2000 Mathematics Subject Classification: 62J12, 62F35

Oxidised LDL lipids, statins and a blood-brain barrier

Elevated cholesterol in mid-life has been associated with increased risk of dementia in later life. We have previously shown that low density lipoprotein (LDL) is more oxidised in the plasma of dementia patients although total cholesterol levels remained unchanged. Increased systemic oxidative modification (oxLDL) and nitration is also observed during hypercholesterolemia. We have investigated the hypothesis that disruption of blood brain barrier (BBB) function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention can mitigate the effects of hyperlipidaemia in mid-life. LDL isolated from statin-naïve hypercholesterolaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and 8-isoprostane F2α concentration (43.5±8.42pg/ml) compared to control subjects (Rf; 0.46±0.05 and 24.2±5.37pg/ml respectively; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hypercholesterolaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased cellular glutathione levels (18.5nmol/mg v 12.3nmol/mg) compared to untreated cells (26.2±3.6nmol/mg). LDL-lipids isolated from normolipidaemic subjects shows reduced risk to damage a BBB model compared with LDL-lipids from hypercholesterolaemic subjects. Moreover, a three month statin-intervention reduced the propensity for LDL-lipids from subjects with hyperlipidaemia to damage HMVEC. Post-statin treatment the cytotoxic and pro-inflammatory effects of LDL lipids disappeared. These data support the hypothesis that in vivo intervention with statins modifies LDL lipid oxidation, exerting a protective effect against in microvascular damage independent of cholesterol concentration.

Modified lipids from LDL in the blood during mid-life increase blood brain barrier permeability

Low density lipoprotein levels (LDL) are consistently elevated in cardiovascular disease. It has been suggested that those with high circulating LDL levels in mid-life may be susceptible to develop neurodegenerative diseases in later life. In the circulation, high levels of LDL are associated with increased oxidative modification (oxLDL) and nitration. We have investigated the hypothesis that disruption of blood brain barrier function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention in mid-life can mitigate the neurodegenerative effects of hyperlipidaemia. Blood from statin-naïve, normo- and hyperlipidaemic subjects (n=10/group) was collected at baseline. Hyperlipidaemic subjects received statin-intervention whereas normolipidaemic subjects did not prior to a second blood sampling, taken after 3 months. The intervention will be completed in June 2013. Plasma was separated by centrifugation (200g, 30min) and LDL was isolated by potassium bromide density gradient ultracentrifugation. Total homocysteine, LDL cholesterol, 8-isoprostane F2α levels were measured in plasma using commercial kits. LDL were analysed by agarose gel electrophoresis. LDL-lipids were extracted by partitioning in 1:1 chloroform:methanol (v/v) and conjugated to fatty acid free-BSA in serum-free EGM-2 medium (4hrs, 370C) for co-culture with human microvascular endothelial cells (HMVEC). HMVEC were maintained on polycarbonate inserts for two weeks to create a microvascular barrier. Change in barrier permeability was measured by trans-endothelial electrical resistance (TER), FITC-dextran permeability and immunohistochemistry. HMVEC glutathione (GSH) levels were measured after 2 hours by GSH-glo assay. LDL isolated from statin-naïve hyperlipidaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and plasma 8-isoprostane F2α (43.5±8.42 pg/ml) compared to control subjects (0.46±0.05 and 24.2±5.37 pg/ml; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hyperlipidaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased GSH (18.5 nmol/mg v 12.3 nmol/mg; untreated cells 26.2±3.6 nmol/mg).

Elemental analysis of glass and ink by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser induced breakdown spectroscopy (LIBS)

The necessity of elemental analysis techniques to solve forensic problems continues to expand as the samples collected from crime scenes grow in complexity. Laser ablation ICP-MS (LA-ICP-MS) has been shown to provide a high degree of discrimination between samples that originate from different sources. In the first part of this research, two laser ablation ICP-MS systems were compared, one using a nanosecond laser and another a femtosecond laser source for the forensic analysis of glass. The results showed that femtosecond LA-ICP-MS did not provide significant improvements in terms of accuracy, precision and discrimination, however femtosecond LA-ICP-MS did provide lower detection limits. In addition, it was determined that even for femtosecond LA-ICP-MS an internal standard should be utilized to obtain accurate analytical results for glass analyses. In the second part, a method using laser induced breakdown spectroscopy (LIBS) for the forensic analysis of glass was shown to provide excellent discrimination for a glass set consisting of 41 automotive fragments. The discrimination power was compared to two of the leading elemental analysis techniques, μXRF and LA-ICP-MS, and the results were similar; all methods generated >99% discrimination and the pairs found indistinguishable were similar. An extensive data analysis approach for LIBS glass analyses was developed to minimize Type I and II errors en route to a recommendation of 10 ratios to be used for glass comparisons. Finally, a LA-ICP-MS method for the qualitative analysis and discrimination of gel ink sources was developed and tested for a set of ink samples. In the first discrimination study, qualitative analysis was used to obtain 95.6% discrimination for a blind study consisting of 45 black gel ink samples provided by the United States Secret Service. A 0.4% false exclusion (Type I) error rate and a 3.9% false inclusion (Type II) error rate was obtained for this discrimination study. In the second discrimination study, 99% discrimination power was achieved for a black gel ink pen set consisting of 24 self collected samples. The two pairs found to be indistinguishable came from the same source of origin (the same manufacturer and type of pen purchased in different locations). It was also found that gel ink from the same pen, regardless of the age, was indistinguishable as were gel ink pens (four pens) originating from the same pack.

Blood-brain barrier in vitro model: A tissue engineering approach and validation

This dissertation evaluated the feasibility of using commercially available immortalized cell lines in building a tissue engineered in vitro blood-brain barrier (BBB) co-culture model for preliminary drug development studies. Mouse endothelial cell line and rat astrocyte cell lines purchased from American Type Culture Collections (ATCC) were the building blocks of the co-culture model. An astrocyte derived acellular extracellular matrix (aECM) was introduced in the co-culture model to provide a novel in vitro biomimetic basement membrane for the endothelial cells to form endothelial tight junctions. Trans-endothelial electrical resistance (TEER) and solute mass transport studies were engaged to quantitatively evaluate the tight junction formation on the in-vitro BBB models. Immuno-fluorescence microscopy and Western Blot analysis were used to qualitatively verify the in vitro expression of occludin, one of the earliest discovered tight junction proteins. Experimental data from a total of 12 experiments conclusively showed that the novel BBB in vitro co-culture model with the astrocyte derived aECM (CO+aECM) was promising in terms of establishing tight junction formation represented by TEER values, transport profiles and tight junction protein expression when compared with traditional co-culture (CO) model setups and endothelial cells cultured alone. Experimental data were also found to be comparable with several existing in vitro BBB models built from various methods. In vitro colorimetric sulforhodamine B (SRB) assay revealed that the co-cultured samples with aECM resulted in less cell loss on the basal sides of the insert membranes than that from traditional co-culture samples. The novel tissue engineering approach using immortalized cell lines with the addition of aECM was proven to be a relevant alternative to the traditional BBB in vitro modeling.

The discrimination and association of float glass and the quantitative analysis of liquids from aerosols and microdrops using laser induced breakdown spectroscopy

Glass is a common form of trace evidence found at many scenes of crimes in the form of small fragments. These glass fragments can transfer to surrounding objects and/or persons and may provide forensic investigators valuable information to link a suspect to the scene of a crime. Since the elemental composition of different glass sources can be very similar, a highly discriminating technique is required to distinguish between fragments that have originated from different sources. ^ The research presented here demonstrates that Laser Induced Breakdown Spectroscopy (LIBS) is a viable analytical technique for the association and discrimination of glass fragments. The first part of this research describes the optimization of the LIBS experiments including the use of different laser wavelengths to investigate laser-material interaction. The use of a 266 nm excitation laser provided the best analytical figures of merit with minimal damage to the sample. The resulting analytical figures of merit are presented. The second part of this research evaluated the sensitivity of LIBS to associate or discriminate float glass samples originating from the same manufacturing plants and produced at approximately the same time period. Two different sample sets were analyzed ranging in manufacturing dates from days to years apart. Eighteen (18) atomic emission lines corresponding to the elements Sr, K, Fe, Ca, Al, Ba, Na, Mg and Ti, were chosen because of their detection above the method detection limits and for presenting differences between the samples. Ten elemental ratios producing the most discrimination were selected for each set. When all the ratios are combined in a comparison, 99% of the possible pairs were discriminated using the optimized LIBS method generating typical analytical precisions of ∼5% RSD. ^ The final study consisted of the development of a new approach for the use of LIBS as a quantitative analysis of ultra-low volume solution analysis using aerosols and microdrops. Laser induced breakdown spectroscopy demonstrated to be an effective technique for the analysis of as low as 90 pL for microdrop LIBS with 1 pg absolute LOD and 20 µL for aerosol LIBS with an absolute LOD of ∼100 fg.^

Targeted Brain Derived Neurotropic Factors (BDNF) Delivery across the Blood-Brain Barrier for Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effectivein-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.

Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood–brain barrier

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.

Acclimatization of the tropical reef coral Acropora millepora to hyperthermal stress

The demise of reef-building corals potentially lies on the horizon, given ongoing climate change amid other anthropogenic environmental stressors. If corals cannot acclimatize or adapt to changing conditions, dramatic declines in the extent and health of the living reefs are expected within the next half century. The primary and proximal global threat to corals is climate change. Reef-building corals are dependent upon a nutritional symbiosis with photosynthetic dinoflagellates belonging to the group Symbiodinium. . The symbiosis between the cnidarian host and algal partner is a stress-sensitive relationship; temperatures just 1°C above normal thermal maxima can result in the breakdown of the symbiosis, resulting in coral bleaching (the loss of Symbiodinium and/or associated photopigments) and ultimately, colony death. As ocean temperatures continue to rise, corals will either acclimatize or adapt to changing conditions, or will perish. By experimentally preconditioning the coral Acropora millepora via sublethal heat treatment, the coral acquired thermal tolerance, resisting bleaching during subsequent hyperthermal stress. The complex nature of the coral holobiont translates to multiple possible explanations for acclimatization: acquired thermal tolerance could potentially originate from the host itself, the Symbiodinium, or from the bacterial community associated with the coral. By examining the type of in hospite Symbiodinium and the bacterial community prior acclimation and after thermal challenge, it is shown that short-term acclimatization is not due to a distinct change in the dinoflagellate or prokaryote community. Though the microbial partnerships remain without considerable flux in preconditioned corals, the host transcriptome is dynamic. One dominant pattern was the apparent tuning of gene expression observed between preconditioned and non-preconditioned treatments, showing a modulated transcriptomic response to stress. Additionally several genes were upregulated in association with thermal tolerance, including antiapoptotic genes, lectins, and oxidative stress response genes. Upstream of two of these thermal tolerance genes, inhibitor of NFκB and mannose-binding lectin, DNA polymorphisms were identified which vary significantly between the northern and southern Great Barrier Reef. The impact of these mutations in putative promoter regions remains to be seen, but variation across thermally-disparate geography serves to generate hypotheses regarding the role of regulatory element evolution in a coral adaptation context.