bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum leptin levels during pregnancy in multiple sclerosis
Authors: Neuteboom RF , Verbraak E , Voerman JSA , van Meurs M , Steegers EAP , de Groot CJM , Laman JD , Hintzen RQ 
Published: August 2009

Background Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity. Objective The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity. Methods Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay. Results Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml ( P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS ( P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women ( P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse ( P = 0.008). Conclusion In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.
Bayesian design using adult data to augment pediatric trials
Authors: Schoenfeld David A , Hui Zheng  , Finkelstein Dianne M 
Published: August 2009

Background It can be difficult to conduct pediatric clinical trials because there is often a low incidence of the disease in children, making accrual slow or infeasible. In addition, low mortality and morbidity in this population make it impractical to achieve adequate power. In this case, the only evidence for treatment efficacy comes from adult trials. Since pediatric care providers are accustomed to relying on evidence from adult studies, it is natural to consider borrowing information from adult trials. Purpose The goal of this article is to propose a Bayesian approach to the design and analysis of pediatric trials to allow borrowing strength from previous or simultaneous adult trials. Methods We apply a hierarchical model for which the efficacy parameter from the adult trial and that of the pediatric trail are considered to be draws from a normal distribution. The choice of (the variance of) this distribution is guided by discussion with medical experts. We show that with this information, one can calculate the sample size required for the pediatric trial. We discuss how inference of these studies in pediatric populations depends on the parameter that captures the similarity of the treatment efficacy in adults compared to children. Results The Bayesian approach can substantially increase the power of a pediatric clinical trial (or equivalently decrease the number of subjects required) by formally leveraging the data from the adult trial. Limitations Our method relies on obtaining a value for the inter-study variability, ν, which may be difficult to describe to a clinical investigator. Conclusions The Bayesian approach has the potential of making pediatric clinical trials feasible because it has the effect of borrowing strength from adult trials, thus requiring a smaller pediatric trial to show efficacy of a drug in children. Clinical Trials 2009; 6: 297—304. http://ctj.sagepub.com
A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display
Authors: Baskar Sivasubramanian , Suschak Jessica M. , Samija Ivan , Srinivasan Ramaprasad , Childs Richard W. , Pavletic Steven Z. , Bishop Michael R. , Rader Christoph 
Published: August 2009

Abstract
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.
Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal
Authors: Heuser Michael , Sly Laura M. , Argiropoulos Bob , Kuchenbauer Florian , Lai Courteney , Weng Andrew , Leung Malina , Lin Grace , Brookes Christy , Fung Stephen , Valk Peter J. , Delwel Ruud , Löwenberg Bob , Krystal Gerald , Humphries R. Keith 
Published: August 2009

Abstract
Although the cancer stem cell (CSC) concept implies that CSCs are rare, recent reports suggest that CSCs may be frequent in some cancers. We hypothesized that the proportion of leukemia stem cells would vary as a function of the number of dysregulated pathways. Constitutive expression of MN1 served as a 1-oncogene model, and coexpression of MN1 and a HOX gene served as a 2-oncogene model. Leukemia-initiating cell (LIC) number and in vitro expansion potential of LICs were functionally assessed by limiting dilution analyses. LIC expansion potential was 132-fold increased in the 2- compared with the 1-oncogene model, although phenotypically, both leukemias were similar. The 2-oncogene model was characterized by granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity and activated STAT/ERK signaling. GM-CSF hypersensitivity of the 2-oncogene model (MN1/HOXA9) was lost in Stat5b−/− cells, and the LIC expansion potential was reduced by 86- and 28-fold in Stat5b−/− and Stat1−/− cells, respectively. Interestingly, in 201 acute myeloid leukemia (AML) patients, coexpression of MN1 and HOXA9 was restricted to patients with the poorest prognosis and was associated with highly active STAT signaling. Our data demonstrate the functional heterogeneity of LICs and show that STAT signaling is critical for leukemia stem cell self-renewal in MN1- and HOXA9-expressing leukemias.
Formation of 1,2-Bis(1-methyl-1,4-dihydro-4-pyridinylidene)cyclobutane by Dehydrogenated Intermolecular Cyclization of 4-Vinyl-1-methylpyridinyl Radical
Authors: Muramatsu Takashi , Toyota Azumao , Satou Yusuke 
Published: August 2009

Abstract
The one-electron reduction of 4-vinyl-1-methylpyridinium bromide with sodium amalgam in degassed acetonitrile at 0 °C leads to the formation of 1,2-bis(1-methyl-1,4-dihydro-4-pyridinylidene)cyclobutane, which is characterized by means of 1H NMR, 13C NMR, and UV–vis absorption spectroscopy.
Aquacatalytic Aerobic Oxidation of Benzylic Alcohols with a Self-supported Bipyridyl–Palladium Complex
Authors: Osako Takao , Uozumi Yasuhiro 
Published: August 2009

Abstract
The aerobic oxidation of alcohols was promoted in water under atmospheric molecular oxygen by a readily recyclable self-supported bipyridyl–palladium polymeric complex, which was prepared via construction of a metal–organic framework (MOF) of a bipyridyl–palladium complex bearing carboxylic groups and a copper(II) linker.
Placental expression of proteases and their inhibitors in patients with HELLP syndrome
Authors: von Steinburg Stephanie Pildner , Krüger Achim , Fischer Thorsten , Mario Schneider Karl-Theodor , Schmitt Manfred 
Published: August 2009

Abstract
In preeclampsia and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, impaired trophoblast invasion and excessive fibrin deposition in the placental intervillous space is associated with fetal compromise. However, little information is available whether modulation of placental protease expression – potentially causing impaired trophoblast invasion – is associated with the HELLP syndrome. Total RNA and protein were extracted from placental tissue from 11 females with HELLP syndrome and 8 controls matched for gestational age. mRNA expression of matrix metalloprotease (MMP) -2 and -9, tissue inhibitors of metalloprotease (TIMP) -1, -2, and -3, and urokinase-type plasminogen activator receptor (uPAR) was determined by Northern blotting. Protein expression of MMP-2 and -9, and TIMP-1 and -2 was detected by Western blotting and that of uPA, uPAR, and plasminogen activator inhibitor (PAI) -1 by ELISA. In patients with HELLP syndrome, mRNA expression of MMP-2 and TIMP-2 was decreased, whereas TIMP-1 and -3 levels were unchanged. MMP-9 and uPAR mRNA was undetectable in both groups. Protein expression of all investigated proteolytic factors remained unchanged. Our findings at the mRNA level suggest a decrease in matrix remodeling in placentae from patients with HELLP syndrome compared with control pregnancies, although this is not supported at the protein level.
CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts – a bioinformatical analysis
Authors: Xiao Ke , Jehle Franz , Peters Christoph , Reinheckel Thomas , Schirmer R. Heiner , Dandekar Thomas 
Published: August 2009

Abstract
In genome-wide screens we studied CA/C1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). For Plasmodium falciparum and P. berghei, several new CA/C1 peptidase genes encoding proteases of the L- and B-family with specific promoter modules were identified. In addition, two new human CA/C1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of CA/C1 peptidase genes in man and mouse seem to be complete now. In each species studied there is a multitude of CA/C1 peptidases with lysosomal localization signals and partial functional overlap according to similar but subfamily-specific structures. Individual target structures in plasmodia include residues specifically different in CA/C1 peptidase subsite 2. This is of medical interest considering CA/C1 peptidase inhibition for chemotherapy in malaria, malignancies and other diseases. Promoter structures and mRNA regulation differ widely among CA/C1 peptidase subfamilies and between mammals and plasmodia. We characterized promoter modules conserved in mouse and man for the CA/C1 peptidase families B and L (with the L-like subfamily, F-like subfamily and mouse-specific J-like subfamily). RNA motif searches revealed conserved regulatory elements such as GAIT elements; plasmodial CA/C1 peptidase mRNA elements include ARE elements and mammalian mRNAs contain 15-lox DICE elements.
Ultrafast memory loss and relaxation processes in hydrogen-bonded systems
Authors: Elsaesser Thomas 
Published: August 2009

Abstract
Structural memory of aqueous systems, such as neat water and biomolecules, in an aqueous environment is strongly influenced by hydrogen bond dynamics. Vibrational spectroscopy in the femtosecond (fs) time domain is applied to map structural dynamics in real-time and identify underlying molecular interactions. Neat liquid water displays an ultrafast loss of structural memory with the fastest decay of structural correlations occurring in the sub-100 fs regime. Both OH stretching and bending excitations of water molecules decay on a subpicosecond time scale, followed by dissipation of excess energy in the hydrogen bond network within a few picoseconds. Water shells around fully hydrated DNA show similar although slightly slower dynamics. A detailed study of hydration shells around ionic phosphate groups in the DNA backbone demonstrates a strong phosphate-water coupling and a subpicosecond rearrangement of hydrogen bonds upon energy disposal. Hydration shells serve as primary heat sinks for excess energy.
Plasmodium falciparum glyoxalase II: Theorell-Chance product inhibition patterns, rate-limiting substrate binding via Arg257/Lys260, and unmasking of acid-base catalysis
Authors: Urscher Miriam , Deponte Marcel 
Published: August 2009

Abstract
Glyoxalase II (GloII) is a ubiquitous thioester hydrolase catalyzing the last step of the glutathione-dependent conversion of 2-oxoaldehydes to 2-hydroxycarboxylic acids. Here, we present a detailed structure-function analysis of cGloII from the malaria parasite Plasmodium falciparum. The activity of the enzyme was salt-sensitive and pH-log k
cat and pH-log k
cat/K
m profiles revealed acid-base catalysis. An acidic pK
a
app value of approximately 6 probably reflects hydroxide formation at the metal center. The glutathione-binding site was analyzed by site-directed mutagenesis. Substitution of residue Arg154 caused a 2.5-fold increase of K
m
app, whereas replacements of Arg257 or Lys260 were far more detrimental. Although the glutathione-binding site and the catalytic center are separated, six of six single mutations at the substrate-binding site decreased the k
cat
app value. Furthermore, product inhibition studies support a Theorell-Chance Bi Bi mechanism with glutathione as the second product. We conclude that the substrate is predominantly bound via ionic interactions with the conserved residues Arg257 and Lys260, and that correct substrate binding is a pH- and salt-dependent rate-limiting step for catalysis. The presented mechanistic model is presumably also valid for GloII from many other organisms. Our study could be valuable for drug development strategies and enhances the understanding of the chemistry of binuclear metallohydrolases.
A Predictive Solubility Tool for Pesticide Emulsifiable Concentrate Formulations
Authors: Kozuki Y. , Ohtsubo T. 
Published: August 2009

Abstract
Emulsifiable concentrates (ECs) are one of the most widely used pesticide formulations because they have a lot of advantages, such as good storage stability, relatively high biological activity, easy weighing, easy production, and so on. An EC is normally prepared by dissolving a pesticide in a nonpolar solvent with surfactants. When a pesticide is hardly soluble in a common nonpolar solvent, a polar solvent is used as a co-solvent. One of the preferred polar solvents, which have been used for this purpose is N-methyl-2-pyrrolidone (NMP). However, because of its toxic profile, which has recently become apparent, the commercial use of NMP is recently restricted in many fields. Under the circumstances, it is desirable to look for an alternative solvent in the pesticide formulation area. The organic conceptual diagram was tried to search for the alternative solvents because it is a useful tool for predicting the physico-chemical properties of an organic compound. In the organic conceptual diagram, the physico-chemical properties are expressed by the combination of the organic value (OV) and the inorganic value (IV). According to the theory, organic compounds that have similar IV/OV ratios (the inorganic organic balance=IOB) are mutually miscible in each other. In order to investigate the applicability of this concept to search for a suitable solvent for a pesticide that is hardly soluble in nonpolar solvents, the relationship of the IOB between two hardly soluble pesticides (i.e., a neonicotinoid insecticide and an herbicide) and several types of solvents was evaluated. As expected, solvents having an IOB close to the targeted pesticide showed high solvency against it, while the pesticide did not dissolve in solvents, which have an IOB farther off. It was demonstrated that the organic conceptual diagram can be a good tool for the selection of a solvent for a pesticide that is hardly soluble in the usual nonpolar solvents.
Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks
Authors: Celiz Mary D. , Tso Jerry , Aga Diana S. 
Published: August 2009

AbstractThe occurrence of human and veterinary pharmaceuticals in the environment has been a subject of concern for the past decade because many of these emerging contaminants have been shown to persist in soil and water. Although recent studies indicate that pharmaceutical contaminants can pose long-term ecological risks, many of the investigations regarding risk assessment have only considered the ecotoxicity of the parent drug, with very little attention given to the potential contributions that metabolites may have. The scarcity of available environmental data on the human metabolites excreted into the environment or the microbial metabolites formed during environmental biodegradation of pharmaceutical residues can be attributed to the difficulty in analyzing trace amounts of previously unknown compounds in complex sample matrices. However, with the advent of highly sensitive and powerful analytical instrumentations that have become available commercially, it is likely that an increased number of pharmaceutical metabolites will be identified and included in environmental risk assessment. The present study will present a critical review of available literature on pharmaceutical metabolites, primarily focusing on their analysis and toxicological significance. It is also intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples. This review aims to provide insight on what future directions might be taken to help scientists in this challenging task of enhancing the available data on the fate, behavior, and ecotoxicity of pharmaceutical metabolites in the environment.
On the Lense-Thirring test with the Mars Global Surveyor in the gravitational field of Mars
Authors: Iorio Lorenzo 
Published: August 2009

Abstract
I discuss some aspects of a recent frame-dragging test performed by exploiting the Root-Mean-Square (RMS) orbit-overlap differences of the out-of-plane component (N) of the Mars Global Surveyor (MGS) spacecraft’s orbit in the gravitational field of Mars. A linear fit to the complete time series for the entire MGS data set (4 February 1999–14 January 2005) yields a normalized slope 1.03 ± 0.41 (with 95% confidence bounds). Other linear fits to different data sets confirm agreement with general relativity. Huge systematic effects induced by mismodeling the martian gravitational field which have been claimed by some authors are absent in the MGS out-of-plane record. The same level of effect is seen for both the classical non-gravitational and relativistic gravitomagnetic forces on the in-plane MGS orbital components; this is not the case for the out-of-plane components. Moreover, the non-conservative forces experience high-frequency variations which are not important in the present case where secular effects are relevant.
Electron Trapping in Higher Adduct Fullerene‐Based Solar Cells
Authors: Lenes Martijn , Shelton Steve W. , Sieval Alex B. , Kronholm David F. , Hummelen Jan C. (Kees) , Blom Paul W. M. 
Published: August 2009

AbstractHere, the performance of bulk‐heterojunction solar cells based on a series of bisadduct analogues of commonly used derivatives of C60 and C70, such PCBMs and their thienyl versions, is investigated. Due to their higher lowest unoccupied molecular orbital an increase in open‐circuit voltage and thus performance is expected. It is shown that the occurrence of a multitude of different isomers results in a decrease in the electron transport for some of the materials. Surprisingly, the solar‐cell characteristics are very similar for all materials. This apparent discrepancy is explained by a significant amount of shallow trapping occurring in the fullerene phase that does not hamper the solar cell performance due the filling of these shallow traps during illumination. Furthermore, the trisadduct analogue of [60]PCBM has been investigated, which, despite an even further increase in open‐circuit voltage, results in a significantly reduced device performance due to a strong deterioration of the electron mobility in the fullerene phase.
The Coming of Advanced Materials: A Personal View of the Contributions by Cambridge Scientists
Authors: Thomas John Meurig 
Published: August 2009

AbstractThe highly significant contributions both directly and indirectly made to the study of condensed matter in general and to advanced materials in particular by a succession of Cambridge scientists over the early years of the past half century are adumbrated in the light of the conjunction of the 21st anniversary of the founding of this journal and the 800th anniversary of the University of Cambridge. So also are the reasons for the burgeoning growth in the last few decades of the preparation, characterization, and use of various kinds of advanced materials. A summary is also given of the author's own work in solid‐state and materials science, including a brief appraisal of recent strategies for the design of advanced catalysts for the production (under environmentally benign conditions) of a number of industrially important chemicals ranging from vitamins to commodities, such as adipic acid and terephthalic acid, and building blocks, such as styrene oxide, that are utilized in the manufacture of cosmetics and perfumes.
Enhanced nanofluidization by alternating electric fields
Authors: Lepek Daniel , Valverde Jose Manuel , Pfeffer Robert , Dave Rajesh N. 
Published: August 2009

AbstractWe show experimental results on a proposed technique to enhance the fluidization of nanoparticle beds. This technique consists of the application of an alternating electric field to the nanofluidized bed. Three different field configurations have been tested: co‐flow field, cross‐flow field, and variable field configurations. Nanoparticle agglomerates are naturally charged by contact and tribo charging mechanisms and therefore are agitated by the action of the externally applied field, which enhance fluidization. According to our observations, the best results are obtained for the variable field configuration. In this configuration, the electric field strength is higher at the bottom of the bed, whereas it is almost negligible at the free surface. Thus, the larger agglomerates, which tend to sink at the bottom of the bed due to stratification, and usually impede uniform fluidization, are strongly agitated. It is thought that the strong agitation of the bigger agglomerates that usually sink to the bottom of the bed contributes to further homogenize the distribution of the gas flow within the bed by destabilizing the development of gas channels close to the gas distributor. On the other hand, the smaller agglomerates at the vicinity of the free surface are just weakly excited. Consequently, fluidization is greatly enhanced, whereas at the same time excessive elutriation is avoided. It is demonstrated that this technique is even suitable to achieve highly expanded fluidization of unsieved nanopowder samples even though the fluidization state returns to be heterogeneous upon the electric field being turned off. © 2009 American Institute of Chemical Engineers AIChE J, 2010