bluuebunny/crossref_metadata_2025_split huggingface dataset:
A statistical approach for array CGH data analysis
Authors: Picard Franck , Robin Stephane , Lavielle Marc , Vaisse Christian , Daudin Jean-Jacques 
Published: February 2005

Abstract
Background
Microarray-CGH experiments are used to detect and map chromosomal imbalances, by hybridizing targets of genomic DNA from a test and a reference sample to sequences immobilized on a slide. These probes are genomic DNA sequences (BACs) that are mapped on the genome. The signal has a spatial coherence that can be handled by specific statistical tools. Segmentation methods seem to be a natural framework for this purpose. A CGH profile can be viewed as a succession of segments that represent homogeneous regions in the genome whose BACs share the same relative copy number on average. We model a CGH profile by a random Gaussian process whose distribution parameters are affected by abrupt changes at unknown coordinates. Two major problems arise : to determine which parameters are affected by the abrupt changes (the mean and the variance, or the mean only), and the selection of the number of segments in the profile.

Results
We demonstrate that existing methods for estimating the number of segments are not well adapted in the case of array CGH data, and we propose an adaptive criterion that detects previously mapped chromosomal aberrations. The performances of this method are discussed based on simulations and publicly available data sets. Then we discuss the choice of modeling for array CGH data and show that the model with a homogeneous variance is adapted to this context.

Conclusions
Array CGH data analysis is an emerging field that needs appropriate statistical tools. Process segmentation and model selection provide a theoretical framework that allows precise biological interpretations. Adaptive methods for model selection give promising results concerning the estimation of the number of altered regions on the genome.
The responses of Ht22 cells to oxidative stress induced by buthionine sulfoximine (BSO)
Authors: Chen Jun , Small-Howard Andrea , Yin Amy , Berry Marla J 
Published: February 2005

Abstract
Background
glutathione (GSH) is the most abundant thiol antioxidant in mammalian cells. It directly reacts with reactive oxygen species (ROS), functions as a cofactor of antioxidant enzymes, and maintains thiol redox potential in cells. GSH depletion has been implicated in the pathogenesis of neurological diseases, particularly to Parkinson's disease (PD). The purpose of this study was to investigate the change of cellular antioxidant status and basic cell functions in the relatively early stages of GSH depletion.

Results
in this study, GSH was depleted by inhibition of glutamylcysteine synthetase using buthionine sulfoximine (BSO) treatment in Ht22, a neuronal cell line derived from mouse hippocampus. Treatment with BSO produced dose-dependent decreases in total GSH level, Fe3+-reducing ability (FRAP assay), Cu2+-reducing ability (Antioxidant Potential, AOP assay), and ABTS free radical scavenging ability (ABTS assay) of the cells, but the sensitivity of these indicators to dosage varied considerably. Most of the changes were completed during the first 8 hours of treatment. Cell viability was tested by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) assay, and cells at lower density in culture were found to be more sensitive to GSH depletion. The activity of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and copper/zinc superoxide dismutase (Cu/Zn-SOD) were affected by GSH depletion. A cDNA expression array assay of the effects of BSO treatment showed significantly decreased mRNA level for 3 genes, and significantly increased mRNA level for 10 genes, including the antioxidant enzymes Cu/Zn-SOD and thioredoxin peroxidase 2 (TPxII).

Conclusions
the study suggests that there are BSO-sensitive and BSO-resistant pools of GSH in Ht22 cells, and that different categories of antioxidant react differently to GSH depletion. Further, the effect of GSH status on cell viability is cell density dependent. Finally, the alterations in expression or activity of several antioxidant enzymes provide insight into the various cellular responses to GSH depletion.
Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis
Authors: Gan Wen Qi , Man SF Paul , Sin Don D 
Published: February 2005

Abstract
Background
Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial. We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.

Methods
We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies. If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data. In the absence of significant heterogeneity, a fixed effects model was used.

Results
We identified six original studies that met the inclusion criteria (N = 162 participants). In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts. In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.

Conclusions
Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD.
Lewis Base-Catalyzed Michael Reactions between Trimethylsilyl Enolate and α,β-Unsaturated Carbonyl Compounds
Authors: Nakagawa Takashi , Fujisawa Hidehiko , Nagata Yuzo , Mukaiyama Teruaki 
Published: February 2005

Abstract
Michael reactions between trimethylsilyl enolates and α,β-unsaturated carbonyl compounds by using a Lewis base catalyst such as lithium benzamide 4 or lithium succinimide 5 in DMF proceeded smoothly to afford the corresponding Michael-adducts in good to high yields (Tables 1–3). In order to extend the scope, Michael reactions catalyzed by lithium acetate (AcOLi), a weak and readily available Lewis base, were studied in detail. AcOLi behaved as an effective Lewis base catalyst in Michael reactions between trimethylsilyl enolates and α,β-unsaturated carbonyl compounds at 0 °C or at room temperature (Tables 4–6). Hindered α,β-unsaturated ketones behaved as excellent Michael-acceptors in the above reaction at room temperature (Table 5). This catalytic Michael reaction also proceeds smoothly in the presence of other lithium carboxylates that are easily prepared in situ by treating carboxylic acids with lithium carbonate (Li2CO3) (Scheme 2). This is the first example of Lewis base-catalyzed Michael reactions between α,β-unsaturated carbonyl compounds and trimethylsilyl enolates.
The uptake of HIV post-exposure prophylaxis within a sexual assault setting in Sydney, Australia
Authors: Templeton David J , Davies S C , Garvin A L , Garsia R J 
Published: February 2005

Our aim was to compare the assault characteristics of victims presenting to a sexual assault service who were prescribed HIV post-exposure prophylaxis (HIV PEP) with those not prescribed HIV PEP. A retrospective review was carried out of the medical records of victims who were seen over a 12-month period in 1999/2000. HIV PEP may have been potentially appropriate for 117 victims, of whom nine (7.7%) were prescribed PEP (eight women, one man). There was a trend for prescription of PEP to depend on the type of assault, with those suffering anal penetration most likely to be prescribed PEP, followed by those with vaginal, and then oral penetration ( P=0.08). Those who gave a history of oral or vaginal mucosal contact with ejaculate were more likely to receive PEP compared with those in whom ejaculation occurred at a non-mucosal site ( P=0.03). Most prescribed PEP regimens involved three antiretroviral drugs. In this study, HIV PEP, when prescribed, was in accord with existing guidelines. Future studies should aim to better document HIV seroconversions in victims of sexual assault and HIV seroprevalence in assailants.
Discovery of drug candidates from some Turkish plants and conservation of biodiversity
Authors: Şener Bilge , Orhan İlkay 
Published: February 2005

Abstract
Discovery for the advancement of medicine and understanding of life sciences constitutes one of the most powerful ways in which biodiversity can contribute to human society. Bioresources have tremendous potential in providing bioactive compounds for the development of new lead candidates for pharmaceuticals, nutraceuticals, and agrochemicals. Therefore, natural products continue to be an important source of modern drugs in clinical use as an active ingredient, starting material to produce semi-synthetic drugs as well as templates for totally synthetic drugs.
The key to success for discovering therapeutic agents from bioresources is based on bioassay-directed isolation techniques. High-throughput screening tests and mechanism-based screening protocols as well as information of folkloric utilization of plants have led to the discovery of lead compounds as drug candidates. Given the current research and development performance associated with the understanding of disease process, there is still a great need for novel compounds with unique mechanisms of action to treat diseases such as cancer, Alzheimer’s disease, arthritis, diabetes, etc. The lecture will highlight bioactive compounds arising from the screening of some Turkish plant extracts.
Due to human population growth and economic pressure, the loss of the earth’s biodiversity is one of the most pressing environmental and development issues today. IUPAC-approved recommendations for global cooperation on sustainable utilization and conservation of biodiversity will also be presented as the dissemination effort of the recommendation.
Biodiversity as a source of new pharmacophores: A new theory of memory III
Authors: Atta-ur-Rahman  , Choudhary M. Iqbal 
Published: February 2005

Abstract
Several classes of natural products with significant inhibitory activity against target enzymes involved in several diseases have been identified. Spectrophotometer and high-throughput assays were used to assess the inhibition of prolyl endopeptidase (PEP), which led us to some novel inhibitors having potential as anticancer agents. Inhibition of cholinesterase enzymes has led to the discovery of new inhibitors with potential for use in Alzheimer’s disease and other neurological disorders. We have also discovered several potent antioxidant agents from natural sources by using a battery of antioxidant assays. Anti-inflammatory activity of a number of natural products was assayed through a cell-based in vitro bioassay. This article also contains a section on a slightly different topic of chemical basis of memory as presented during the lecture. The theory of the chemical basis of memory based on hydrogen bonding in the brain is further elaborated.
Approaches to the stereoselective total synthesis of biologically active natural products
Authors: Baron Anne , Ball Matthew , Bradshaw Benjamin , Donnelly Sam , Germay Olivier , Oller Pilar C. , Kumar Naresh , Martin Nathaniel , O’Brien Matthew , Omori Hiroki , Moore Christopher , Thomas Eric J. 
Published: February 2005

Abstract
Total syntheses of epothilone B and pamamycin 607, which feature reactions between functionalized allylstannanes and aldehydes to introduce a (Z)-trisubstituted double-bond and remote stereocenters stereoselectively, are discussed. Recent work concerned with carrying out this chemistry without the use of allylstannanes as starting materials and progress toward a total synthesis of bryostatins are also presented.
Chemistry of tetrathiomolybdate and tetraselenotungstate: Applications in carbohydrate chemistry
Authors: Ramu Sridhar Perali , Saravanan V. , Chandrasekaran S. 
Published: February 2005

Abstract
An efficient one pot synthesis of thio and selenolevoglucosans from 1,6-diactivated carbohydrate derivatives has been achieved using benzyltriethylammonium tetrathiomolybdate, [BnNEt3]2MoS4, as a sulfur transfer reagent and tetraethylammonium tetraselenotungstate, [Et4N]2WSe4, as a selenium transfer reagent, respectively. The methodology has also been extended to the synthesis of 1,5-epithio and 1,5-episeleno pentoses.
Indo-U.S. collaborative studies on biocatalytic generation of novel molecular architectures
Authors: Watterson Arthur C. , Parmar Virinder S. , Kumar Rajesh , Sharma Sunil K. , Shakil Najam A. , Tyagi Rahul , Sharma Ajendra K. , Samuelson Lynne A. , Kumar Jayant , Nicolosi Robert , Shea Thomas 
Published: February 2005

Abstract
Biocatalytic polymerization reactions on a variety of substrates leading to value-added polymers have been summarized. The main focus of this review is on the control of molecular architecture during enzymatic polymerization reactions. Combined with chemical reactions, several extremely flexible chemo-enzymatic synthetic procedures are described to produce families of new polymeric materials with novel properties. The properties of the synthesized polymers and their applications in various fields, such as drug delivery and flame retardant materials, have also been studied and discussed.
Biocatalytic routes toward pharmaceutically important precursors and novel polymeric systems
Authors: Sharma Sunil K. , Husain Mofazzal , Kumar Rajesh , Samuelson Lynne A. , Kumar Jayant , Watterson Arthur C. , Parmar Virinder S. 
Published: February 2005

Abstract
The synthetic potential of enzymes related to organic synthesis has been applied profusely, especially since the introduction of their use in organic solvents. Enzymes offer the opportunity to carry out highly chemo-, regio-, and enantioselective transformations. The use of enzymes in the synthetic sequence provides unique advantages of efficiency and environmental friendliness. Owing to their low cost and applicability to a broad range of substrates, lipases have become the most versatile class of biocatalysts in organic synthesis. We have screened a battery of lipases to carry out highly selective reactions for the synthesis of a wide range of organic compounds and polymeric materials.
Biocatalytic synthesis of novel electronic and photovoltaic materials
Authors: Mosurkal Ravi , Kumar Rajesh , Bruno Ferdinando F. , Nagarajan Ramaswamy , Samuelson Lynne , Kumar Jayant 
Published: February 2005

Abstract
A new class of ruthenium complex-based macrodye and a dinuclear complex were synthesized via a biocatalytic route employing hematin as an efficient biocatalyst. The photovoltaic overall efficiency of the dinuclear complex was found to be 2.1 % and higher than the polymeric complex (0.33 %). Furthermore, we have developed an environmentally benign methodology for the synthesis of novel pegylated polyphenolics. The reaction conditions used do not require any organic solvents, and all the reactions were performed in aqueous media. The synthesized polymers were soluble in both organic and aqueous media, and provide further opportunity to tailor the properties. Finally, a novel biomimetic method for the synthesis of a conducting molecular complex of polypyrrole and of thiophene substitute in the presence of a polyelectrolyte, such as polystyrene sulfonate (SPS), is presented. A synthetic enzyme based on hematin was used to catalyze the polymerization of pyrrole (PYR) and 3,4-ethylenedioxythiophene (EDOT) in the presence of SPS. Copolymers of EDOT and PYR have also been synthesized, and these novel materials have been shown to exhibit high electrical conductivity.
Biocatalytic production of flavors and fragrances
Authors: Franssen Maurice C. R. , Alessandrini Laura , Terraneo Giancarlo 
Published: February 2005

Abstract
The preparation of flavors and fragrances has to be done with great care. When these compounds are meant for consumption, no toxic chemicals are allowed during their preparation. For use in non-food additives, a high purity is required. Both constraints can be easily fulfilled when enzymes are used as catalyst during the production of these compounds. This paper summarizes the work that we have done regarding the preparation of branched-chain fatty acids (sheep flavors) using lipases, the production of glucosides (controlled-release flavors) using glucosidases, the formation of terpene alcohols and grapefruit flavor using enzymes from chicory, and the formation of phenolic antioxidants using lipases.
Plasmodium falciparum triosephosphate isomerase: New insights into an old enzyme
Authors: Ravindra Gudihal , Balaram Padmanabhan 
Published: February 2005

Abstract
Triosephosphate isomerase (TIM), a central enzyme in the glycolytic pathway, has been the subject of extensive structural and mechanistic investigations over the past 30 years. The TIM barrel is the prototype of the (β/α)8 barrel fold, which is one of the most extensively used structural motifs in enzymes. Mechanistic studies on TIM from a variety of sources have emphasized the importance of loop 6 dynamics for enzyme activity. Several conserved residues in TIM have been investigated by extensive site-directed mutagenesis of the enzyme from yeast, chicken, and trypanosoma. The cloning and sequencing of the TIM gene from the malarial parasite Plasmodium falciparum in 1993 revealed the unexpected mutation of a hitherto conserved residue serine (S96) to phenylalanine (F96). Subsequent results from the genome sequencing programs of Plasmodium falciparum, Plasmodium vivax, and Plasmodium yoelii confirmed the presence of the S96F mutation in malarial parasites. The crystal structure of PfTIM and several inhibitor complexes, including a high-resolution (1.1 Å) structure of the PfTIM 2-phosphoglycerate complex, revealed that loop 6 had a propensity to remain open, even in several ligand bound structures. Furthermore, both open and closed forms could be characterized for the same complex. Since glycolysis is the primary source of ATP for the malarial parasite during the intraerythrocytic stage, glycolytic enzymes present themselves as potential targets for inhibitors. Two distinct approaches have been explored. The use of dimer interface peptides, which interfere with assembly, has proved promising. Inactivation of the enzyme by modification of a cysteine (C13) residue, which lies close to the active site residue, lysine (K12) is another potential strategy. The differential reactivity, of the four-cysteine residues, at positions 13, 126, 196, and 217 in each subunit has been established using electrospray ionization mass spectrometry. Studies of single tryptophan mutants (W11F and W168F) of PfTIM provide a probe to study folding, stability, and inhibitor interactions.
Forced intercalation as a tool in gene diagnostics and in studying DNA–protein interactions
Authors: Köhler Olaf , Jarikote Dilip V. , Singh Ishwar , Parmar Virinder S. , Weinhold Elmar , Seitz Oliver 
Published: February 2005

Abstract
Aromatic and heteroaromatic groups that are forced to intercalate at specific positions in DNA are versatile probes of DNA–DNA and DNA–protein recognition. Fluorescent nucleobases are of value since they are able to report on localized alterations of DNA duplex structure. However, the fluorescence of the vast majority of base surrogates becomes quenched upon intercalation in DNA. Peptide nucleic acid (PNA)-based probes are presented in which the intercalator dye thiazole orange (TO) serves as a fluorescent base surrogate. In these probes, fluorescence increases (5–60-fold) upon hybridization. PNA-bearing TO as fluorescent base surrogate could hence prove useful in real-time polymerase chain reaction (PCR) applications and in live cell analysis. Forced intercalation of aromatic polycycles can help to explore the binding mechanism of DNA-modifying enzymes. We discuss studies of DNA-methyltransferases (MTases) which commence methylation of nucleobases in DNA by flipping the target nucleotide completely out of the helix. A method for probing the base-flipping mechanism is suggested. It draws upon the observation that large hydrophobic base surrogates in the face of the swung-out base can enhance the DNA-enzyme binding affinity possibly by disrupting target base-stacking and stabilizing the apparent abasic site.
Age-Related Variations in Acylcarnitine and Free Carnitine Concentrations Measured by Tandem Mass Spectrometry
Authors: Cavedon Catia Testa , Bourdoux Pierre , Mertens Karl , Van Thi Hong Vien , Herremans Nadine , de Laet Corinne , Goyens Philippe 
Published: February 2005

AbstractBackground: The acylcarnitine profiles obtained from dried blood spots on “Guthrie cards” have been widely used for the diagnosis and follow-up of children suspected of carrying an inherited error of metabolism, but little attention has been paid to potential age-related variations in the reference values. In this study, we evaluated the variations in free carnitine and acylcarnitine concentrations with age, as measured by tandem mass spectrometry.Methods: Filter-paper blood spots were collected from 433 healthy individuals over a period of 17 months. Eight age groups were defined: cord blood, 3–6 days (control group), 15–55 days, 2–18 months, 19–59 months, 5–10 years, 11–17 years, and 18–54 years. Free carnitine and acylcarnitines were measured for each individual. Mean values were calculated for each age group and compared with those for the control group.Results: Free carnitine was significantly higher in older children than in newborns (P &lt;0.05), but the concentrations of several acylcarnitines tended to be significantly lower in cord blood and in groups of older children than in the control group. Only minor sex-related differences were observed.Conclusion: Although the risk of underdiagnosis of fatty acid oxidation disorders with the use of newborn values as reference can be considered as small, in some circumstances the use of age-related reference values may have a potential impact on the diagnosis and management of inherited errors of metabolism.
Canadian Liquefaction Experiment (CANLEX): Blast-Induced Ground Motion and Pore Pressure Experiments
Authors: Al-Qasimi EMA , Charlie WA , Woeller DJ 
Published: February 2005

Abstract
As part of the Canadian Liquefaction Experiment (CANLEX), single and multiple explosive charges were detonated in a level deposit of loose, saturated, sand-size mine tailings. Empirical equations were developed from pore pressure and ground motion recorded at several locations. A condition of zero effective stress was induced at a depth of 6 m when peak particle velocity exceeded 0.65 m/s for single detonations and 0.13 m/s for twelve detonations having millisecond delays. Little or no excess pore pressure was induced from single or multiple detonations when peak particle velocity or peak compressive strain was less than 0.01 m/s or 0.001 %, respectively. The blasting experiments were conducted and analyzed to determine blast-induced ground motion and pore pressure response in a level deposit and to determine the possibility of using explosives to trigger flow-liquefaction in tailings located below an embankment, while keeping peak particle velocities within limits set by Syncrude Canada, Ltd.