Thermal Pretreatment of Wood for Co-gasification/co-firing of Biomass and Coal

Utilization of biomass as a co-feed in coal and biomass co-firing and co-gasification requires size reduction of the biomass. Reducing biomass to below 0.2 mm without pretreatment is difficult and costly because biomass is fibrous and compressible. Torrefaction is a promising thermal pretreatment process and has the advantages of increasing energy density, improving grindability, producing fuels with more homogenous compositions and hydrophobic behavior. Temperature is the most important factor for the torrefaction process. Biomass grindability is related to cell wall structure, thickness and composition. Thermal treatment such as torrefaction can cause chemical changes that significantly affect the strength of biomass. The objectives of this study are to understand the mechanism by which torrefaction improves the grindability of biomass and discuss suitable temperatures for thermal pretreatment for co-gasification/cofiring of biomass and coal. Wild cherry wood was selected as the model for this study. Samples were prepared by sawing a single tangential section from the heartwood and cutting it into eleven pieces. The samples were consecutively heated at 220, 260, 300, 350, 450 and 550oC for 0.5 hr under flowing nitrogen in a tube furnace. Untreated and treated samples were characterized for physical properties (color, dimensions and weight), microstructural changes by SEM, and cell wall composition changes and thermal behaviors by TGA and DSC. The morphology of the wood remained intact through the treatment range but the cell walls were thinner. Thermal treatments were observed to decompose the cell wall components. Hemicellulose decomposed over the range of ~200 to 300oC and resulted in weakening of the cell walls and subsequently improved grindability. Furthermore, wood samples treated above 300oC lost more than 39% in mass. Therefore, thermal pretreatment above the hemicelluloses decomposition temperature but below 300oC is probably sufficient to improve grindability and retain energy value

Tumor cell invasion of model 3‐dimensional matrices: demonstration of migratory pathways, collagen disruption, and intercellular cooperation

We report a novel 3‐dimensional model for visualizing tumor cell migration across a nylon mesh‐supported gelatin matrix. To visualize migration across these model barriers, cell proteolytic activity of the pericellular matrix was detected using Bodipy‐BSA (fluorescent upon proteolysis) and DQ™ collagen (fluorescent upon collagenase activity). For 3‐dimensional image reconstruction, multiple optical images at sequential z axis positions were deconvoluted by computer analysis. Specificity was indicated using well‐known inhibitors. Using these fluorescent proteolysis markers and imaging methods, we have directly demonstrated proteolytic and collagenolytic activity during tumor cell invasion. Moreover, it is possible to visualize migratory pathways followed by tumor cells during matrix invasion. Using cells of differing invasive potentials (uPAR‐negative T‐47D wild‐type and uPAR‐positive T‐47D A2–1 cells), we show that the presence of the T‐47D‐A2–1 cells facilitates the entry of T‐47D wild‐type cells into the matrix. In some cases, wild‐type cells follow T‐47D A2–1 cells into the matrix whereas other T‐47D‐wild‐type cells appear to enter without the direct intervention of T‐47D A2–1 cells. Thus, we have developed a new 3‐dimensional model of tumor cell invasion, demonstrated protein and collagen disruption, mapped the pathways followed by tumor cells during migration through an extracellular matrix, and illustrated cross‐talk among tumor cell populations during invasion.—Horino, K., Kindezelskii, A. L., Elner, V. M., Hughes, B. A., Petty, H. R. Tumor cell invasion of model 3‐dimensional matrices: demonstration of migratory pathways, collagen disruption, and intercellular cooperation. FASEB J. 15, 932–939 (2001)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154275/1/fsb2fj000392com.pd

Functional Analysis of Novel Polymorphisms in the Human SLCO1A2 Gene that Encodes the Transporter OATP1A2

The solute carrier organic anion transporting polypeptide 1A2 (OATP1A2, SLCO1A2) is implicated in the cellular influx of a number of drugs. We identified five novel single nucleotide polymorphisms (SNPs) in coding exons of the SLCO1A2 gene in a cohort of subjects: G550A, G553A, G673A, A775C, and G862A, that encoded the OATP1A2 variants E184K, D185N, V255I, T259P, and D288N, respectively. The function and expression of these variant transporters were assessed in HEK-293 cells. We found that the novel variants, E184K, D185N, T259P, and D288N, were associated with impaired estrone-3-sulfate, imatinib, and methotrexate transport (∼20-50% of wild-type control); function was retained by OATP1A2-V255I. From biotinylation assays, the decreased function of these variants was due, at least in part, to impaired plasma membrane expression. The four loss-of-function variants were studied further using mutagenesis to produce variants that encode residues with different charges or steric properties. From immunoblotting, the replacement of negatively charged residues at amino acid positions 184 and 185 impaired membrane expression, while either a positive or negative charge at residue 288 supported the correct membrane targeting of OATP1A2. Replacement of T259 with bulky residues disrupted transporter stability. From molecular models, E184, D185, and D288 were located near several charged residues such that intramolecular ionic interactions may stabilize the transporter structure. Individuals who carry these novel SNPs in the SLCO1A2 gene may be at risk from impaired efficacy or enhanced toxicity during treatment with drugs that are substrates for OATP1A2.This study was supported by grants from Cancer Council NSW and the Australian National Health and Medical Research Council. The generous gifts of imatinib and 14C-imatinib from Novartis are gratefully acknowledged

Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments

Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore, human POS binding to human RPE cells elicited transmembrane metabolic and calcium signals within RPE cells, which could be blocked by saturating doses of an inhibitory anti-TLR4 mAb. However, the heterologous combination of bovine POS and human RPE did not trigger these signals. The pattern recognition receptor CD36 collected at the POS–RPE cell interface for both homologous and heterologous samples, but human TLR4 only collected at the human POS–human RPE cell interface. Kinetic experiments of human POS binding to human RPE cells revealed that CD36 arrives at the POS–RPE interface followed by TLR4 accumulation within 2 min. Metabolic and calcium signals immediately follow. Similarly, the production of reactive oxygen metabolites (ROMs) was observed for the homologous human system, but not the heterologous bovine POS–human RPE cell system. As (a) the bovine POS/human RPE combination did not elicit TLR4 accumulation, RPE signaling, or ROM release, (b) TLR4 arrives at the POS–RPE cell interface just before signaling, (c) TLR4 blockade with an inhibitory anti-TLR4 mAb inhibited TLR4 clustering, signaling, and ROM release in the human POS–human RPE system, and (d) TLR4 demonstrates similar clustering and signaling responses to POS in confluent RPE monolayers, we suggest that TLR4 of RPE cells participates in transmembrane signaling events that contribute to the management of human POS

Evaluation of Risk for Late Language Emergence after In Utero Antiretroviral Drug Exposure in HIV-exposed Uninfected Infants

This is not the published version.BACKGROUND Combination antiretroviral (cARV) regimens are recommended for pregnant women with HIV to prevent perinatal HIV transmission. Safety is a concern for infants who were HIV-exposed but uninfected (HEU), particularly for neurodevelopmental problems, such as language delays. METHODS We studied late language emergence (LLE) in HEU children enrolled in a US-based prospective cohort study. LLE was defined as a caregiver-reported score ≤ 10th percentile in any of 4 domains of the MacArthur-Bates Communicative Development Inventory for one-year-olds and as ≥1 standard deviation below age-specific norms for the Ages and Stages Questionnaire for two-year-olds. Logistic regression models were used to evaluate associations of in utero cARV exposure with LLE, adjusting for infant, maternal, and environmental characteristics. RESULTS 1,129 language assessments were conducted among 792 one- and two-year-olds (50% male, 62% black, and 37% Hispanic). Overall, 86% had in utero exposure to cARV and 83% to protease inhibitors. LLE was identified in 26% of one-year-olds and 23% of two-year-olds, with higher rates among boys. In adjusted models, LLE was not associated with maternal cARV or ARV drug classes in either age group. Among cARV-exposed one-year-olds, increased odds of LLE was observed for those exposed to atazanavir (aOR=1.83, 95% CI=1.10-3.04), particularly after the first trimester (aOR=3.56, p=0.001), compared to atazanavir-unexposed infants. No associations of individual ARV drugs with LLE were observed among two-year-olds. CONCLUSIONS In utero cARV exposure showed little association with LLE, except for a higher risk of language delay observed in one-year-old infants with atazanavir exposure

Development of membranes for hydrogen separation: Pd-coated V-10Pd

Numerous Group IVB and VB alloys were prepared and tested as potential membrane materials but most of these materials were brittle or exhibited cracking during hydrogen exposure. One of the more ductile alloys, V-10Pd (at. %), was fabricated into a thin (107-{micro}m thick) composite membrane coated with 100 nm of Pd on each side. The material was tested for hydrogen permeability, resistance to hydrogen embrittlement, and long term hydrogen flux stability. The hydrogen permeability, {phi}, of the V-10Pd membrane was 3.86 x 10{sup -8} mol H{sub 2} m{sup -1} s{sup -1} Pa{sup -0.5} (avg. of three different samples) at 400 C, which is slightly higher than the permeability of Pd-23Ag at that temperature. A 1400 h hydrogen flux test at 400 C demonstrated that the rate of metallic interdiffusion was slow between the V-10Pd foil and the 100-nm-thick Pd coating on the surface. However, at the end of testing the membrane cracked at 118 C because of hydrogen embrittlement

Language Impairment in Children Perinatally Infected with HIV Compared to Children Who Were HIV-Exposed and Uninfected

OBJECTIVE: To investigate risk for language impairment in children perinatally infected or exposed to HIV. METHOD: We evaluated the prevalence of language impairment (LI) in 7–16 year old children with perinatal HIV infection (HIV+) compared to children HIV-exposed and uninfected (HEU), using a comprehensive standardized language test (CELF-4). LI was classified as primary LI (Pri-LI) (monolingual English exposure and no cognitive or hearing impairment), concurrent LI (Con-LI) (cognitive or hearing impairment), or no LI. Associations of demographic, caregiver, HIV disease and antiretroviral treatment (ART) factors with LI category were evaluated using univariate and multivariable logistic regression models. RESULTS: Of 468 children with language assessments, 184 (39%) had LI. No difference was observed by HIV infection status for overall LI or for Pri-LI or Con-LI; mean (SD) CELF-4 scores were 88.5 (18.4) for HIV+ vs 87.5 (17.9) for HEU. After adjustment, Black children had higher odds of Pri-LI vs no LI (aOR=2.43, p=0.03). Children who were Black, Hispanic, had a caregiver with low education or low IQ, or a non-biological parent as caregiver had higher odds of Con-LI vs no LI. Among HIV+ children, viral load >400 copies/ml (aOR=3.04, p<0.001), CDC Class C (aOR=2.19, p=0.02) and ART initiation <6 months of age (aOR=2.12, p=0.02) were associated with higher odds of Con-LI vs. no LI. CONCLUSIONS: Children perinatally exposed to HIV are at high risk for LI, but such risk was not increased for youth with HIV. Risk factors differed for Pri-LI and Con-LI

Language Impairment in Children Perinatally Infected with HIV Compared to Children Who Were HIV-Exposed and Uninfected

Objective - To investigate risk for language impairment in children perinatally infected or exposed to HIV. Methods - We evaluated the prevalence of language impairment (LI) in 7–16 year old children with perinatal HIV infection (HIV+) compared to children HIV-exposed and uninfected (HEU), using a comprehensive standardized language test (CELF-4). LI was classified as primary LI (Pri-LI) (monolingual English exposure and no cognitive or hearing impairment), concurrent LI (Con-LI) (cognitive or hearing impairment), or no LI. Associations of demographic, caregiver, HIV disease and antiretroviral treatment (ART) factors with LI category were evaluated using univariate and multivariable logistic regression models. Results - Of 468 children with language assessments, 184 (39%) had LI. No difference was observed by HIV infection status for overall LI or for Pri-LI or Con-LI; mean (SD) CELF-4 scores were 88.5 (18.4) for HIV+ vs 87.5 (17.9) for HEU. After adjustment, Black children had higher odds of Pri-LI vs no LI (aOR=2.43, p=0.03). Children who were Black, Hispanic, had a caregiver with low education or low IQ, or a non-biological parent as caregiver had higher odds of Con-LI vs no LI. Among HIV+ children, viral load \u3e400 copies/ml (aOR=3.04, pp=0.02) and ART initiation (aOR=2.12, p=0.02) were associated with higher odds of Con-LI vs. no LI. Conclusions - Children perinatally exposed to HIV are at high risk for LI, but such risk was not increased for youth with HIV. Risk factors differed for Pri-LI and Con-LI