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Influence of question type on response adequacy in young adults with autism.

Sources of difficulty in comprehending conversational questions for individuals with autism may be multifarious, given the complexity of the disorder. This study investigated success in responding to naturalistic conversational questions by six young adults with autism, using a quantitative discourse analytic method. Subjects, aged 19-21, who were able to converse in at least simple sentences, were engaged in conversation about events and activities in their lives. From the transcripts of these conversations, four types of questions were isolated for analysis: more than seven words in length; multiclausal; requiring inference; and indirect requests for information. It was predicted that inference-based questions would be more difficult than the other types. Findings did not support this prediction. All four types showed a higher failure rate than the overall failure rate for responses to conversational questions. Clinical implications include the need for conversational assessment of receptive language functioning for individuals with autism. Suggestions for such assessments are provided.

Adult↗

Conversion of food waste into hydrogen by thermophilic acidogenesis.

Conversion of food waste into hydrogen by thermophilic acidogenesis was investigated as a function of organic loading rate (OLR), hydraulic retention time (HRT) and pH in a continuous stirred tank reactor. In order to identify hydrogen-producing microorganisms, denaturing gradient gel electrophoresis (DGGE) of the polymerase chain reaction (PCR)--amplified V3 region of 16S rDNA analysis was conducted at each tested pH. The conversion of food waste into hydrogen was strongly influenced by the operational conditions. The hydrogen production was increased as OLR increased up to 8 gVSl(-1) d(-1), but drastically decreased at 10 gVSl(-1) d(-1). The yield of hydrogen was decreased from 2.2 to 1.0 mol-H2/mol-hexose consumed as HRT decreased from 5 to 2 days. More carbohydrates in the food waste were decomposed at longer HRT, 76-90%, at HRT of 2-5 days. The hydrogen production peaked at pH 5.5+/-0.1 and significantly decreased at pH 5.0+/-0.1. The biogas produced was composed of hydrogen and carbon dioxide, but no methane was detected at all tested conditions. The hydrogen contents in the gas produced were more than 55% (v/v) and not sensitive to all tested conditions. The optimum operational condition for continuous hydrogen production from the food waste was obtained at 8 gVSl(-1)d(-1), 5 days HRT and pH 5.5+/-0.1 where the hydrogen production rate, content, yield and the efficiency of carbohydrate decomposition were 1.01 H2/l-d, 60.5% (v/v), 2.2 mol-H2/mol-hexose consumed and 90%, respectively. The hydrogen production was related with the concentration of total organic acids (TOA) which was strongly dependent on that of butyrate indicating that the reaction was mainly butyrate fermentation. The hydrogen-producing microorganism of Thermoanaerobacterium thermosaccharolyticum that involved in acetate/butyrate fermentation, was detected with strong intensity at all tested pHs by denaturing gradient gel electrophoresis (DGGE) of the polymerase chain reaction (PCR)--amplified V3 region of 16S rDNA analysis and sensitive to the tested pHs. The experimental results indicated that effective hydrogen production from the food waste could be obtained continuously by thermophilic acidogenesis at proper operational condition.

Acids↗

Thermal stability, Judd-Ofelt theory analysis and spectroscopic properties of a new Er3+/Yb3+-codoped germano-tellurite glass.

The Er3+/Yb3+-codoped 70TeO2-5Li2O-10B2O3-15GeO2 glass was prepared. The thermal stability, absorption spectra, emission spectra and up-conversion spectra were measured and investigated. The Judd-Ofelt analysis based on absorption spectra was performed in order to determine the Judd-Ofelt intensity parameters Omega(t) (t = 2, 4, 6), spontaneous emission probability, radiative lifetime and branching ratios of several Er3+ transitions. It was found that this studied glass has good thermal stability, broad fluorescence full width at half maximum (FWHM), large stimulated emission cross-section and strong up-conversion emissions at about 532, 546 and 659 nm, corresponding to the 2H(11/2)-->4I(15/2), 4S(3/2)-->4I(15/2) and 4F(9/2)-->4I(15/2) transitions of Er3+, respectively under the excitation at 970 nm. The results suggest that this Er3+/Yb3+-codoped germano-tellurite glass may be a potentially useful material for developing potential amplifiers and up-conversion optical devices.

Cations, Monovalent↗

Insights into glandular trichome biology from analysis of organ-specific gene expression programmes in cannabis, hop and tomato.

Glandular trichomes (GTs) are epidermal outgrowths in which diverse specialised (secondary) metabolites are synthesised and stored. Cannabis (Cannabis sativa L.) and its close relative hop (Humulus lupulus L.) have pharmaceutical and industrial significance due to the presence of these metabolites in their GTs. We examined the conservation or divergence of the specific transcriptional programmes underlying GT biology. To achieve this, we generated transcriptome atlases of trichomes, flower, leaf, stem and root for cannabis, hop and tomato. We found that 12.9, 10.1 and 16.8% of cannabis, hop and tomato genes, respectively, were expressed organ/tissue specifically across all organs/tissues. Transcription factors (TFs) on average accounted for 7.5% of the organ-specific transcriptome and likely regulate organ-specific functions. We also conducted weighted gene co-expression network analysis and gene regulatory network (GRN) analysis to identify key regulators of GT function across the species and validated our predictions by DNA affinity purification sequencing for a subset of the cannabis and tomato GT TFs. The GRNs specific to cannabis or hop GTs were enriched for TFs and target genes associated with specialised metabolism, reflecting their species-specific nature. Conversely, the shared GRN components (identified via orthology analysis) were involved in highly conserved processes, such as flavonoid biosynthesis, solute transport and metabolite storage. Together, these GRNs and the associated transcriptome atlases are valuable resources to improve our knowledge of GT function and organ-specific genome regulation.

Solanum lycopersicum↗

Frozen shell approximation violation in negative ion formation from halogenated benzenes via dissociative attachment

A series of benzene derivatives (R(1)C(6)H(4)R(2)) has been studied by means of electron capture negative ion mass spectrometry (ECNI-MS), and PM3 quantum chemical calculations. The dissociation channel M(-.) --> Hal(-) + (M - Hal). is analysed from the point of view of symmetry conservation. Generally, a symmetry ban on dissociation may be avoided in at least two ways: (i) out-of-plane vibrations of the halogen atom in the molecular negative ion (MNI), mixing pi- and sigma-states of the anion; (ii) symmetrical in-plane vibration of the C-Hal bond, changing the order of the empty levels in the MNI with subsequent radiationless conversion into a sigma-state. Our analysis shows that neither of them provides a satisfactory explanation of the ECNI mass spectra for chlorobenzene, if one retains the usual assumption that an additional electron goes into the LUMO of the neutral molecule. Thus, it may be concluded that in this case electron capture causes a significant perturbation of the energy ordering of vacant orbitals, thus making the frozen shell approximation inapplicable. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Rapid biocatalytic polytransesterification: reaction kinetics in an exothermic reaction

Biocatalytic polytransesterification at high concentrations of monomers proceeds rapidly and is accompanied by an increase in the temperature of the reaction mixture due to liberation of heat of reaction during the initial phase. We have used principles of reaction calorimetry to monitor the kinetics of polymerization during this initial phase, thus relating the temperature to the extent of polymerization. Rate of polymerization increases with the concentration of monomers. This is also reflected by the increase in the temperature of the reaction mixture. Using time-temperature-conversion contours, a differential method of kinetic analysis was used to calculate the energy of activation ( approximately 15.1 Kcal/mol). Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

Liquid chromatography/electrospray tandem mass spectrometry method for the quantitation of fosinoprilat in human serum using automated 96-well solid-phase extraction for sample preparation.

A sensitive, specific, accurate and reproducible liquid chromatography/electrospray tandem mass spectrometry method was developed and validated for the quantitation of fosinoprilat in 0.2 mL of human serum. The method employed acidification (with pH 4.0 sodium acetate buffer) of the serum samples to minimize the hydrolysis of the prodrug fosinopril to fosinoprilat prior to purification by automated 96-well solid-phase extraction. The required chromatographic separation of fosinoprilat and fosinopril was achieved isocratically on a Luna C8 analytical column (2 x 50 mm, 3 microm). The total run time was 2 min. The mobile phase contained methanol and water with 10 mM ammonium acetate. Detection was by positive ion electrospray tandem mass spectrometry. The standard curve, which ranged from 2.00 to 500 ng/mL, was fitted to a 1/x(2) weighted linear regression model. Fosinoprilat quality control (QC) samples used to determine the accuracy and precision of the method were prepared in human serum at concentrations of 5.00, 200, 400 and 1000 ng/mL. The assay accuracy was within 8% (dev). The intra- and inter-assay precisions were within 6 and 3% (RSD), respectively. Fosinopril QC samples used to gauge the rate of hydrolysis of fosinopril to fosinoprilat during the assay procedure were prepared in human serum at 500 ng/mL. The hydrolysis of fosinopril to fosinoprilat was </=1%. This degree of conversion would cause little error in the analysis of post-dose serum samples since such samples are known to contain low levels of the prodrug compared with the drug.

Analysis of Variance↗

Exposure of women in general populations to lead via food and air in East and Southeast Asia.

BACKGROUND: Despite increasing public concern of the possible health effects of lead (Pb) on general populations, reports on Pb levels in blood (Pb-B) and urine (Pb-B), as well as Pb intake via foods (Pb-F) for many Asian countries are scarce. The present study was initiated to elucidate the extent of non-occupational Pb exposure among general populations in East and Southeast Asia. METHODS: In 1991-1997, peripheral blood, morning spot urine and 24-hour food duplicate samples were collected from 20 to 50 non-smoking adult women in each of four cities in Southeast Asia and five cities in Mainland China, and two cities each in Japan and Korea. The samples were wet-ashed and then analyzed by inductively coupled plasma mass spectrometry for Pb-B, Pb-U and Pb-F. Measures after logarithmic conversion were subjected to ANOVA and regression analysis. RESULTS: Geometric mean values in cities in East and Southeast Asia were in ranges of 32-65 microg/L for Pb-B, 2.1-7.5 microg/g cr for Pb-Ucr, and 7-32 microg/day for Pb-F. The values for a combination of two cities of Tokyo and Kyoto, Japan (38 microg/L for Pb-B and 9.3 microg/day for Pb-F) appeared to be lower than the values for other Asian cities, and the values for all Japan (thus including both urban and rural areas) were even lower (19 microg/L for Pb-B and 7.7 microg/day for Pb-F). Comparison of Pb uptake via respiratory and dietary routes showed that Pb via dietary route accounted for 15% of the total in Manila where Pb in air was high (ca. 650 ng/m(3)), whereas it was 54% in Tokyo+Kyoto where Pb in air was low (ca. 75 ng/m(3)). CONCLUSIONS: When compared internationally, Pb-F and Pb-B in Asia in general are similar to or somewhat higher than the levels in Europe and USA, whereas the levels in Japan are probably lower than the two latter areas. In Asia, Pb-F accounted for 15-54% of all Pb sources, the percentage being variable depending on local conditions especially Pb in atmospheric air.

Adult↗

Identification of methyl farnesoate from in vitro culture of the retrocerebral complex of adult females of the moth, Heliothis virescens (Lepidoptera: Noctuidae) and its conversion to juvenile hormone III.

Gas chromatographic-mass spectral analysis of extracts obtained from in vitro culture of isolated retrocerebral complexes obtained from adult females of the moth Heliothis virescens resulted in identification of methyl farnesoate as well as juvenile hormone III (JH III) but not JH III acid. Inhibition of JH biosynthesis by incubation of tissue in synthetic Manduca sexta allatostatin (Manse-AST, pGlu-Val-Arg-Phe-Arg-Gln-Cys-Tyr-Phe-Asn-Pro-Ile-Ser-Cys-Phe-COOH) reduced production of these chemicals to negligible levels. However, incubation of tissue in the presence of Manse-AST plus farnesol resulted in production of significant amounts of both methyl farnesoate and JH III. Tissue incubated in the presence of Manse-AST plus methyl farnesoate produced only JH III. The results indicated that methyl farnesoate is naturally produced by the corpora allata of adult females of Heliothis virescens. However, tissue incubated in the presence of Manse-AST plus JH III acid also produced JH III in amounts equivalent to that produced by tissue incubated with methyl farnesoate. Thus, both methyl farnesoate and JH III acid could serve as a precursor for biosynthesis of JH III.

Animals↗

European experience with laparoscopic Roux-en-Y gastric bypass in 466 obese patients.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is usually considered as the procedure of choice for morbid obesity, but its use has been limited in Europe. It is not known whether results with European patients match those from the USA. METHODS: A total of 466 patients were followed prospectively regarding weight loss, co-morbidities, quality of life and morbidity after primary laparoscopic RYGBP. Overall assessment was done using the bariatric analysis and reporting outcome system (BAROS). RESULTS: Conversion to open surgery was necessary in three patients. The overall early morbidity rate was 17.0 per cent and the rate of major complications was 4.7 per cent. The mortality rate was 0.2 per cent. Major morbidity decreased over time. Excess weight loss of over 50 per cent was maintained for up to 4 years in 71.4 per cent of the morbidly obese and 65.2 per cent of the super-obese patients. Co-morbidities resolved or improved in most patients and quality of life improved. At 3 years, the BAROS score was excellent or very good in 77.1 per cent and good in 22.8 per cent. Late complications leading to reoperation developed in 19 patients (4.1 per cent). CONCLUSION: These results are satisfactory and comparable to those reported from the USA. Owing to limitations associated with purely restrictive bariatric procedures, laparoscopic RYGBP is likely to become the procedure of choice for treatment of morbid obesity in Europe.

Adolescent↗

Discrimination of fluorinated uridine metabolites in N-417 small cell lung cancer cell extracts via 19F- and 31P-NMR.

31P-NMR extract spectra of N-417 Small Cell Lung Cancer (SCLC) cells cultured with fluorouridine (FUrd) reveal new peaks with chemical shifts in the diphosphodiester and nucleoside triphosphate regions. These peaks were identified as FUTP, FUDP, FUDP-glucose, FUDP-glucuronate, FUDP-GlcNAc, and FUDP-GalNAc via enzymatic conversion and 19F- and 31P-NMR analysis. Distinct 19F chemical shifts were assigned for FUTP, FUDP, and the FUDP-sugars.

Carcinoma, Small Cell↗

Theoretical study of the ligand-CYP2B4 complexes: effect of structure on binding free energies and heme spin state.

The molecular origins of temperature-dependent ligand-binding affinities and ligand-induced heme spin state conversion have been investigated using free energy analysis and DFT calculations for substrates and inhibitors of cytochrome P450 2B4 (CYP2B4), employing models of CYP2B4 based on CYP2C5(3LVdH)/CYP2C9 crystal structures, and the results compared with experiment. DFT calculations indicate that large heme-ligand interactions (ca. -15 kcal/mol) are required for inducing a high to low spin heme transition, which is correlated with large molecular electrostatic potentials (approximately -45 kcal/mol) at the ligand heteroatom. While type II ligands often contain oxygen and nitrogen heteroatoms that ligate heme iron, DFT results indicate that BP and MF heme complexes, with weak substrate-heme interactions (ca. -2 kcal/mol), and modest MEPS minima (>-35 kcal/mol) are high spin. In contrast, heme complexes of the CYP2B4 inhibitor, 4PI, the product of benzphetamine metabolism, DMBP, and water are low spin, have substantial heme-ligand interaction energies (<-15 kcal/mol) and deep MEPS minima (<-45 kcal/mol) near their heteroatoms. MMPBSA analysis of MD trajectories were made to estimate binding free energies of these ligands at the heme binding site of CYP2B4. In order to initially assess the realism of this approach, the binding free energy of 4PI inhibitor was computed and found to be a reasonable agreement with experiment: -7.7 kcal/mol [-7.2 kcal/mol (experiment)]. BP was determined to be a good substrate [-6.3 kcal/mol (with heme-ligand water), -7.3 kcal/mol (without ligand water)/-5.8 kcal/mol (experiment)], whereas the binding of MF was negligible, with only marginal binding binding free energy of -1.7 kcal/mol with 2-MF bound [-3.8 kcal/mol (experiment)], both with and without retained heme-ligand water. Analysis of the free energy components reveal that hydrophobic/nonpolar contributions account for approximately 90% of the total binding free energy of these substrates and are the source of their differential and temperature-dependent CYP2B4 binding. The results indicate the underlying origins of the experimentally observed differential binding affinities of BP and MF, and indicate the plausibility of the use of models derived from moderate sequence identity templates in conjunction with approximate free energy methods in the estimation of ligand-P450 binding affinities.

Amino Acid Sequence↗

Oligodendroblasts distinguished from O-2A glial progenitors by surface phenotype (O4+GalC-) and response to cytokines using signal transducer LIFR beta.

The developmental potential of progenitors at two final stages of the macroglial lineage giving rise to oligodendrocytes in postnatal rat brain was studied in response to defined and serum inducers of astrocyte gene expression. Cell immunoselection [with Gd3 ganglioside, O4 and galactocerebroside (GalC) antibodies] was used to isolate G+D3O4- and O4+GalC- phenotypes directly from premyelinating cerebrum. In a basal defined culture medium, G+D3O4- progenitors differentiated infrequently into oligodendrocytes on a growth substratum comprised of meningeal cell-derived extracellular matrix. Their conversion into astrocytes, as determined by immunofluorescence analysis of glial fibrillary acidic protein expression, was induced by oncostatin-M as well as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, but not interleukin-6, and required extracellular matrix. By comparison, O4+GalC- progenitors were refractory to astrocyte induction under these conditions, as in short-term cultures of optic nerve, and differentiated into myelinogenic oligodendrocytes instead. Only in response to an overriding stimulus in fetal bovine serum did O4+GalC- progenitors, like their immediate precursors, become astrocytic. These data functionally distinguish two classes of astrocyte-inducing agents to provide clear evidence of an oligodendroblast, a progenitor defined by surface phenotype (O4+GalC-) and an altered response of the oligodendrocyte lineage to cytokines using signal transducer LIFR beta.

Animals↗

Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to human genomic diversity.

We have utilized computational biology to screen GenBank for the presence of recently integrated Ya5 and Yb8 Alu family members. Our analysis identified 2640 Ya5 Alu family members and 1852 Yb8 Alu family members from the draft sequence of the human genome. We selected a set of 475 of these elements for detailed analyses. Analysis of the DNA sequences from the individual Alu elements revealed a low level of random mutations within both subfamilies consistent with the recent origin of these elements within the human genome. Polymerase chain reaction assays were used to determine the phylogenetic distribution and human genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8 Alu family members were restricted to the human genome and absent from orthologous positions within the genomes of several non-human primates, confirming the recent origin of these Alu subfamilies in the human genome. Approximately 1 % of the analyzed Ya5 and Yb8 Alu family members had integrated into previously undefined repeated regions of the human genome. Analysis of mosaic Yb8 elements suggests gene conversion played an important role in generating sequence diversity among these elements. Of the 475 evaluated elements, a total of 106 of the Ya5 and Yb8 Alu family members were polymorphic for insertion presence/absence within the genomes of a diverse array of human populations. The newly identified Alu insertion polymorphisms will be useful tools for the study of human genomic diversity.

Alu Elements↗

The role of brush border enzymes in tubular reabsorption of disaccharides: a microperfusion study in rat kidney.

Renal tubular reabsorption of maltose, sucrose and lactose were studied in vivo et situ by continuous microperfusion of single proximal convolutions of rat kidney. The 14C-label of maltose (2.5 mmol/l) was removed from the lumen of the proximal tubule at about the same rate as found for glucose. Maltose reabsorption was completely inhibited in presence of 30 mmol/l glucose or of 0.1 mmol/l phlorizin. Chemical analysis of the samples showed a complete conversion of maltose into glucose within a perfusion distance of 2 mm. It is concluded from these results that within the tubular lumen maltose is split very rapidly by a brush border glucosidase. The short half time of this process permits the breakdown product glucose to be almost completely reabsorbed subsequently within the proximal tubule. In contrast, sucrose and lactose were neither split nor reabsorbed by the tubule brush border.

Animals↗

An intermediate state in hydrolysis of amorphous calcium phosphate.

The hydrolysis of previously prepared amorphous calcium phosphate (ACP) was studied in a solution "saturated" with ACP; this eliminated the initial consumption of acid due to ACP dissolution. The procedure established that conversion of high-concentration ACP slurry to an apatite involves two processes: the first process consumes acid and indicates the formation of a more acidic calcium phosphate intermediary with the solubility of octacalcium phosphate (OCP); the second process consumes base and indicates the conversion of the intermediary to apatite and, possibly, direct conversion of ACP to apatite. The thermodynamic analysis of the solution composition data suggests that ACP converts into a nonstoichiometric apatite when the OCP-like intermediary is formed, and a stoichiometric apatite is formed when no OCP-like intermediary is involved.

Calcium Phosphates↗

Pharmacokinetic evaluation of high-dose etoposide phosphate after a 2-hour infusion in patients with solid tumors.

Etoposide phosphate, a water soluble prodrug of etoposide, was evaluated at levels potentially useful in transplantation settings in patients with malignancies. For pharmacokinetic studies of etoposide phosphate in this phase I study, 21 patients with solid tumors were treated with etoposide phosphate given as etoposide equivalents of 250, 500, 750, 1000 and 1200 mg/m2 infused over 2 h on days 1 and 2, and G-CSF 5 micrograms/kg per day starting on day 3 until WBC was > or = 10,000/microliters. Qualitative, quantitative, and pharmacokinetic analysis was performed as reported previously. Rapid conversion of etoposide phosphate into etoposide by dephosphorylation occurred at all dosage levels without indication of saturation of phosphatases. Plasma levels (C(pmax)) and area under the curve (AUC) of etoposide phosphate and etoposide demonstrated linear dose effects. For etoposide, plasma disposition demonstrated biphasic clearance, with mean T1/2 alpha of 2.09 +/- 0.61 h, and T1/2 beta of 5.83 +/- 1.71 h. An AUC as high as 1768.50 micrograms.h/ml was observed at a dose of 1200 mg/m2. The total body clearance (TBC) showed an overall mean of 15.72 +/- 4.25 ml/min per m2, and mean volume of distribution (VDss) of 5.64 +/- 1.06 l/m2. The mean residual time (MRT) for etoposide was 6.24 +/- 1.61 h. In urine, etoposide but not etoposide phosphate, was identified with large quantitative variations (1.83% to 33.45% of injected etoposide equivalents). These results indicate that etoposide phosphate is converted into etoposide with the linear dose-related C(pmax) and AUCs necessary for use of this agent at the high dosage levels needed in transplantation protocols. A comparison of pharmacokinetic parameters of high-dose etoposide with the values observed in our study with etoposide phosphate revealed comparable values for the clinically important C(pmax) and AUCs, clearance, terminal T1/2 and MRT. In contrast to the use of etoposide, etoposide phosphate can be delivered in aqueous vehicles and therefore may offer the advantage of ease of administration.

Antineoplastic Agents↗

Long-term results of laparoscopic antireflux surgery.

BACKGROUND: It is estimated that laparoscopic antireflux surgery has replaced the open approach in centers worldwide. Findings show it to be an established treatment option for chronic gastroesophageal reflux disease with an excellent clinical outcome and success rates between 85% and 95%. This prospective study aimed to evaluate surgical outcome and analysis of failure after 500 laparoscopic antireflux procedures followed up for as long as 5 years. METHODS: Between September 1993 and May 2000, 500 laparoscopic antireflux procedures were performed in our surgical unit. In 345 patients, a laparoscopic "floppy" Nissen fundoplication was performed, and in 155 patients, a Toupet fundoplication was carried out with standard mobilization of the upper part of the gastric fundus and with division of the short gastric vessels. Preoperative and postoperative data including 24-h pH monitoring, esophageal manometry, and analysis of failure were prospectively reviewed. RESULTS: Conversion to open surgery was necessary in two patients (0.4%). Morbidity was 7%, including 24 patients (4.8%) for whom a laparoscopic redoprocedure was necessary because of failed primary intervention. There was no mortality. During a follow-up period of 3 months to 5 years, 24-h pH monitoring and esophageal manometry showed normal values in 95% of the patients including patients who had undergone redosurgery. CONCLUSION: The results of the current study demonstrate that laparoscopic antireflux surgery is feasible and effective, and that it can be performed safely without mortality and with low morbidity, yielding good to excellent results over a follow-up period up to 5 years.

Adult↗