julilili42/papers huggingface dataset:
Flexible Routes to the 5‐Hydroxy Acid Fragment of the Cryptophycins
2003-04-17

Abstract Two solutions to establishing the anti stereochemistry of the vicinal stereocenters in the 5‐hydroxy acid subunit of cryptophycin, based on initial Evans syn aldol reactions between an N ‐(propionyl)oxazolidinone 4 and a C 3 aldehyde, were developed. In the first route, the secondary hydroxy group was inverted by use of Mitsunobu reaction conditions, whereas the second route features an inversion of the methyl‐bearing stereocenter, achieved by reductive removal of the chiral auxiliary, elimination to afford the terminal alkene, and anti ‐selective hydroboration. The aryl part can be attached either by Wittig−Horner olefination or by a modified Julia coupling. Both routes provide the hydroxy acid 16 in a very efficient manner. The substrate for the hydroboration, alkene 22 , could also be obtained from ( S )‐malic acid. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
The impact of progesterone receptor expression on relapse in the long-term clinical course of 93 benign meningiomas.
2003-04-17

Our findings support previous studies that found an association of low or absent expression of PgR with a higher risk of recurrence. This encourages attempts at a hormonal therapy for patients with PgR-positive meningioma.
Apoptotic Response of Chang Cells to Infection withPseudomonas aeruginosaStrains PAK and PAO-I: Molecular Ordering of the Apoptosis Signaling Cascade and Role of Type IV Pili
2003-04-18

ABSTRACT Pseudomonas aeruginosa is a gram-negative facultative opportunistic pathogen associated with severe infections in immunocompromised hosts and in patients with cystic fibrosis. P. aeruginosa strains show divergent pathogenicity in vivo and trigger apoptosis of and/or are internalized into human host cells. In the present study, we studied the molecular ordering of apoptosis signaling upon infection of human conjunctiva epithelial Chang cells with P. aeruginosa PAK as well as the role of bacterial pili in the response to the infection. Our results show that CD95 up-regulation is followed by early activation of caspase-8 and -3 and cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase. The data also demonstrate release of apoptosis inducing factor into the cytosol of infected cells. Induction of mitochondrial alterations, i.e., mitochondrial depolarization and release of cytochrome c, as well as cleavage of caspase-9, -7, and -1 occurred only at later time points. In addition, our results demonstrate that pili are required for P. aeruginosa -induced apoptosis of human epithelial cells. While the two piliated P. aeruginosa strains, PAO-I and PAK, induced apoptosis of Chang cells within 3 h of infection, the pilus-deficient P. aeruginosa mutants PAKΔ pilA and PAKΔ pilA Δ all were without effect. The pilus-deficient mutants failed to induce a significant up-regulation of CD95 on the cell surface and to trigger mitochondrial alterations or activation of caspase-8, -3, and -7. In addition, only the piliated wild-type strains induced caspase-1-mediated activation of interleukin-1β. Thus, pili are necessary for distinct infection-induced cellular responses of human epithelial cells.
Reply to “Comment on ‘Structure of ferrofluid dynamics’ ”
2003-04-21

Derived from general principles, the recently introduced ferrofluid dynamics is structurally identical to Shliomis' theory for incompressional flows, yet distinctly different for compressional ones. It provides a complementary point of view for the first case, but also shows that the standard theory partially violates general principles. Overemphasizing the competition between both theories while ignoring their factual differences could hinder progress in ferrofluid physics.
Specialized cheating of the ectomycorrhizal symbiosis by an epiparasitic liverwort
2003-04-22

Many non-photosynthetic vascular plants in 10 diverse families obtain all of their carbon from fungi, but in most cases the fungi and the ultimate sources of carbon are unknown. In a few cases, such plants have been shown to be epiparasitic because they obtain carbon from neighbouring green plants through shared mycorrhizal fungi. In all such cases, the epiparasitic plants have been found to specialize upon narrow lineages of ecto- or arbuscular mycorrhizal fungi. Here we show that a non-vascular plant, the non-photosynthetic liverwort Cryptothallus mirabilis, is epiparasitic and is specialized on Tulasnella species that form ectomycorrhizae with surrounding trees at four locations in England, France and Portugal. By using microcosm experiments we show that the interaction with Tulasnella is necessary for growth of Cryptothallus, and by using labelling experiments we show that (14)CO(2) provided to birch seedlings is transferred to Cryptothallus by Tulasnella. This is one of the first documented cases of epiparasitism by a non-vascular plant and of ectomycorrhizal formation by Tulasnella. These results broaden the emerging association between epiparasitism and mycorrhizal specialization into a new class of plants and a new order of fungi.
A recombinant bispecific single‐chain antibody induces targeted, supra‐agonistic CD28‐stimulation and tumor cell killing
2003-04-22

Abstract Endowing tumor cells with costimulatory signals for T cell activation has emerged as a promising strategy for tumor immunotherapy. Costimulatory molecules were either transfected into tumor cells to generate vaccines or were fused, e.g. to antibodies against tumor‐associated antigens, to achieve targeted T cell costimulation in vivo . Here we report the production and purification of rM28, a recombinant bispecific single‐chain antibody directed to a melanoma‐associated proteoglycan and to the costimulatory CD28 molecule on human T cells. We found that a dimer of the recombinant molecule, bound to tumor target cells, induced pronounced T cell activation in peripheral blood mononuclear cell preparations without additional TCR/CD3 stimulation being required. Thelytic activity generated after 3 days of stimulation effectively prevented tumor cell growth. However, it was unspecific and predominantly mediated by non T cells. Our findings demonstrate that presentation of a CD28 antibody within a suitable recombinant, bispecific format may result in a "targeted supra‐agonistic stimulation" of the CD28 molecule, which leads to effective tumor cell killing after induction of unspecifically lytic cells.
Silica‐based monoliths for rapid peptide screening by capillary liquid chromatography hyphenated with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry
2003-04-24

Abstract Capillary liquid chromatography based on particulate and monolithic stationary phases was used to screen complex peptide libraries by fast gradient elution coupled on‐line to electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI‐FTICRMS). A slightly modified commercial electrospray interface consisting of a fused‐silica transfer capillary and low dead volume stainless steel union at which the electrospray voltage was grounded enabled the effluent of all the capillary columns to be directly sprayed into the mass spectrometer. Stable electrospray conditions were generated over a wide range of mobile phase compositions, alleviating the need for a tapered end of the spray capillary, pneumatic assistance or preheated nebulizer gas. Since the identification of complex samples containing numerous isobaric substances is facilitated by chromatographic separation prior to mass spectrometry, stationary phase materials have been employed which offer a fast, efficient elution and, due to the complexity of samples, a high loading capacity. Silica‐based monolithic capillary columns combine these three characteristics in a unique manner due to a tailored adjustment of both macro‐ and mesopore sizes in the highly porous silica structure. As we demonstrate by a comparative study of the silica‐based monolithic and packed capillaries for LC/MS analysis of complex peptide libraries, silica monoliths show superior performance over packed beds of small‐diameter particles with respect to analysis time and separation efficiency. Libraries with more than 1000 different peptides could be screened in less than 20 min. Copyright © 2003 John Wiley &amp; Sons, Ltd.
Identification of Regioisomers in a Series of N-Substituted Pyridin-4-yl Imidazole Derivatives by Regiospecific Synthesis, GC/MS, and 1H NMR
2003-04-25

The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.
Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia
2003-04-28

Abstract NKG2D ligands (NKG2DLs) mark malignant cells for recognition by natural killer (NK) cells and cytotoxic T lymphocytes via the activating immunoreceptor NKG2D. This led to the hypothesis that NKG2DLs play a critical role in tumor immune surveillance. The human NKG2DLs MICA and MICB are expressed on tumors of epithelial origin in vivo. For the other recently described set of human NKG2DLs, the UL16-binding proteins (ULBPs), expression in vivo is as yet undefined. In this study we investigated expression and function of NKG2DLs in leukemia using a panel of newly generated NKG2DL-specific monoclonal antibodies. We report that leukemia cells from patients variously express MIC and ULBP molecules on the cell surface with MICA most frequently detected. Patient leukemia cells expressing MICA were lysed by NK cells in an NKG2D-dependent fashion. Sera of patients, but not of healthy donors, contained elevated levels of soluble MICA (sMICA). We also detected increased sMICB levels in patient sera using a newly established MICB-specific enzyme-linked immunosorbent assay. Reduction of leukemia MIC surface expression by shedding may impair NKG2D-mediated immune surveillance of leukemias. In addition, determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies.
Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning
2003-04-28

Summary. Allogeneic stem cell transplantation (allo‐SCT) after reduced‐intensity conditioning was evaluated in 22 patients (median age 53, range 36–66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)‐identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA‐mismatched unrelated donor]. Graft‐versus‐host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) ( n = 12) or CSA plus mycophenolate mofetil ( n = 10). Despite of heavy pretreatment, the transplant‐related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2–19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8–36 months) post allografting. Estimated 2 year overall and event‐free survival was, respectively, 25·5% and 22·0% for the whole patient group, and 62·5% and 57·1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation ( P = 0·0182) and absence of cGVHD ( P = 0·069) were associated with shorter event‐free survival. Thus long‐term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.
Breaking rotational symmetry in two-flavor color superconductors
2003-04-28

The color superconductivity under flavor asymmetric conditions relevant to\\nthe compact star phenomenology is studied within the Nambu-Jona-Lasinio model.\\nWe focus on the effect of the deformation of the Fermi surfaces on the pairing\\nproperties and the energy budget of the superconducting state. We find that at\\nfinite flavor asymmetries the color superconducting BCS state is unstable\\ntowards spontaneous quadrupole deformation of the Fermi surfaces of the and\\n quarks into ellipsoidal form. The ground state of the phase with deformed\\nFermi surfaces corresponds to a superposition of prolate and oblate deformed\\nFermi ellipsoids of and quarks.\\n
Investigation of a capillary electrophoretic approach for direct quantification of apolipoprotein A‐I in serum
2003-04-28

Abstract In the present study a rapid, reproducible and robust capillary electrophoresis (CE) procedure for the quantification of apolipoprotein A‐I (Apo A‐I) in serum without pretreatment has been developed (total run time, 11 min). The coefficients of variation (CV; n = 10) for the relative peak area are 1.8% at a concentration of 145 mg/dL and 1.6% at 196 mg/dL; and for the inter‐assay 8.9% at 161 mg/dL (10 consecutive days), i.e. , similar to the CVs of a high‐throughput immunonephelometric routine assay. The CV for the migration time is 0.4% ( n = 20). The robustness of the CE approach was tested in patient samples with hemolysis, hyperbilirubinemia and hyperlipidemia. A comparison of 99 Apo A‐I serum values with results of a fixed‐time immunonephelometric routine assay showed a positive constant bias of 60% (mean) for the immunonephelometric values, no deviation from linearity, but significant deviations in several samples. Investigations on interferences in the CE analyses gave no evidence that CE failed. Our study shows that CE is amenable to a fast analysis and a reproducible and reliable quantification of Apo A‐I level in sera of various clinical samples.
( S )‐2‐Chloroalkanoic Acids of High Enantiomeric Purity from ( S )‐2‐Amino Acids: ( S )‐2‐Chloropropanoic Acid
2003-04-28

Abstract ( S )‐2‐Chloroalkanoic acids of high enantiomeric purity from ( S )‐2‐amino acids: ( S )‐2‐chloropropanoic acid product: (S)‐2‐chloropropanoic acid product: (2R,3S)‐2‐chloro‐3‐methylpentanoic acid product: CH3 product: CH(CH3)2 product: CH2CH(CH3)2 product: (3S)‐CH(CH3)CH2CH3
( R )‐Alkyloxiranes of High Enantiomeric Purity from ( S )‐2‐Chloroalkanoic Acids via ( S )‐2‐Chloro‐1‐Alkanols: ( R )‐Methyloxirane
2003-04-28

Abstract ( R )‐Alkyloxiranes of high enantiomeric purity from ( S )‐2‐chloroalkanoic acids via ( S )‐2‐chloro‐1‐alkanols: ( R )‐methyloxirane intermediate: (S)‐2‐Chloropropan‐1‐ol. product: (R)‐Methyloxirane unknown: S)‐methyloxirane
Cyclobutanone via Solvolytic Cyclization
2003-04-28

Abstract Cyclobutanone via solvolytic cyclization reactant: 75 g. (0.27 mole) of trifluoromethanesulfonic anhydride reactant: 15 g. (0.21 mole) of 3‐butyn‐1‐ol reactant: 11.5 g. (0.0846 mole) of sodium trifluoroacetate intermediate: 17 g. (0.084 mole) of 3‐butyn‐1‐yl trifluoromethanesulfonate product: cyclobutanone
D ‐2‐Oxo‐7,7‐dimethyl‐1‐vinylbicyclo[2.2.1]heptane
2003-04-28

Abstract D ‐2‐Oxo‐7,7‐dimethyl‐1‐vinylbicyclo[2.2.1]heptane reactant: 13.0 g. (0.052 mole) of D ‐camphor‐10‐sulfonyl chloride byproduct: Triethylamine hydrochloride intermediate: episulfone product: D ‐2‐Oxo‐7,7‐dimethyl‐1‐vinylbicyclo[2.2.2]heptane
Synthesis and Properties of Hydrophilic Polymers, 10
2003-04-29

Abstract Water‐soluble poly[( N ‐maleoylglycine)‐ co ‐(hydroxyethyl methacrylate)] was employed for the separation of a series of metal ions in the aqueous phase using the liquid‐phase polymer‐based retention method. The method is based on the retention of inorganic ions by this polymer in conjunction with membrane filtration and subsequent separation of low‐molecular‐mass species from the polymer complex formed. It is shown that the polymer can bind several metal ions in aqueous solution at pH 3, 5, and 7, for example Cr(II), Co(II), Zn(II), Ni(II), Cu(II), Cd(II), Pb(II) inorganic ions. The interaction of the inorganic ions with the hydrophilic polymer was determined as a function of pH and filtration factor. The water‐soluble polymeric reagent with strong metal‐complexing properties was synthesized and used to separate complexed from non‐complexed ions in the homogeneous phase. The polymer exhibited high retention capability at pH 5 and 7. It was characterized by elemental analysis, FT‐IR, 1 H NMR, and 13 C NMR spectroscopy, as well as by thermogravimetry. Additionally, viscosimetric measurements of the copolymer were performed at different pH values. magnified image
Correction
2003-04-29

Many waterbodies across the United States do not meet water quality standards. To help determine where and to what extent improvements should be sought, policymakers must consider the costs of regulations with their monetized values. We ...Scientific knowledge related to quantifying the monetized benefits for landscape-wide water quality improvements does not meet current regulatory and benefit–cost analysis needs in the United States. In this study we addressed this knowledge gap by ...
Extending the Applicability of Carboxyfluorescein in Solid-Phase Synthesis
2003-04-30

Optimized coupling protocols are presented for the efficient and automated generation of carboxyfluorescein-labeled peptides. Side products, generated when applying earlier protocols for the in situ activation of carboxyfluorescein, were eliminated by a simple procedure, yielding highly pure fluorescent peptides and minimizing postsynthesis workup. For the cost-efficient labeling of large compound collections, coupling protocols were developed reducing the amount of coupling reagent and fluorophore. To enable further chemical derivatization of carboxyfluorescein-labeled peptides in solid-phase synthesis, the on-resin introduction of the trityl group was devised as a protecting group strategy for carboxyfluorescein. This protecting group strategy was exploited for the synthesis of peptides labeled with two different fluorescent dyes, essential tools for bioanalytical applications based on fluorescence resonance energy transfer (FRET). Tritylation and optimized labeling conditions led to the development of a fluorescein-preloaded resin for the automated synthesis of fluorescein-labeled compound collections with uniform labeling yields.
Geometric numerical integration illustrated by the Störmer–Verlet method
2003-05-01

The subject of geometric numerical integration deals with numerical integrators that preserve geometric properties of the flow of a differential equation, and it explains how structure preservation leads to improved long-time behaviour. This article illustrates concepts and results of geometric numerical integration on the important example of the Störmer–Verlet method. It thus presents a cross-section of the recent monograph by the authors, enriched by some additional material. After an introduction to the Newton–Störmer–Verlet–leapfrog method and its various interpretations, there follows a discussion of geometric properties: reversibility, symplecticity, volume preservation, and conservation of first integrals. The extension to Hamiltonian systems on manifolds is also described. The theoretical foundation relies on a backward error analysis, which translates the geometric properties of the method into the structure of a modified differential equation, whose flow is nearly identical to the numerical method. Combined with results from perturbation theory, this explains the excellent long-time behaviour of the method: long-time energy conservation, linear error growth and preservation of invariant tori in near-integrable systems, a discrete virial theorem, and preservation of adiabatic invariants.
Biology and Plasticity of CD133+ Hematopoietic Stem Cells
2003-05-01

A bstract : AC133 (CD133) is a highly conserved antigen expressed on hematopoietic stem cells with unknown function. In order to further characterize CD133 + progenitor cells, we purified CD133 + stem cells using the method of magnetic activated cell sorting (MACS) from healthy adult volunteers mobilized with granulocyte colony‐stimulating growth factor (G‐CSF) to a mean purity of 94%. The purified CD133 + cells highly engrafted NOD/SCID mice. In addition, unseparated mononuclear cells or CD133 + stem cells isolated from the bone marrow of transplanted NOD/SCID mice gave rise to engraftment of secondary recipients. Upon ex vivo culture of purified CD133 + cells with FLT3/Flk2 ligand (FL) and interleukin‐6 (IL‐6), a plastic‐adherent cell population could be observed after 6 weeks in culture. These adherent cells did not express CD34 or CD133 antigens on their surface, nor did they express markers for endothelial, mesenchymal, or dendritic cells. After incubation of these adherent cells with stem cell factor (SCF), non‐adherent cells were observed which partially co‐expressed CD133, but were negative for CD34. These nonadherent CD34 − cells showed a high engraftment capacity in NOD/SCID mice. From our results, we conclude that CD133 might be a marker of early progenitors with a high NOD/SCID engraftment potential. The fact that CD133 + hematopoietic progenitors can give rise to an adherent population which is CD133 − and CD34 − and that these cells can again give rise to a CD133 + CD34 − stem cell population with high NOD/SCID engraftment potential indicates the plasticity of hematopoietic precursors. CD133 + stem cells might be useful for research and for clinical application.
Identification of a 5‐nucleotide sequence that controls expression of the ica locus in Staphylococcus aureus and characterization of the DNA‐binding properties of IcaR
2003-05-01

Summary Biofilm formation is an important aspect of the pathogenesis of staphylococcal infections. A β‐1,6‐linked N‐acetyl glucosamine polysaccharide is critical to biofilm elaboration and is synthesized by proteins encoded by the intercellular adhesion ( ica ) locu s . These studies were undertaken to characterize the mechanism by which transcription of the ica locus in S. aureus is regulated using isogenic S. aureus MN8 and MN8 mucoid (MN8m) strains, the latter of which constitutively overproduces biofilm. Transformation of the ica locus from MN8m to the ica knock‐out mutants of two strains, MN8 and NCTC 10833, conferred a strong biofilm‐producing phenotype. Sequence analysis revealed a 5‐nucleotide deletion within the promoter region of the ica locus in MN8m compared with the sequence in the wild‐type locus. Deletion or substitution of these 5 nucleotides within the wild‐type ica locus augmented transcription of the ica locus and induced the strong biofilm‐producing phenotype. Gel shift analysis demonstrated that a protein(s) within cell‐free lysates from strain MN8 bind(s) specifically to oligonucleotides representative of the wild‐type ica promoter sequence and that this binding is greatly diminished by the deletion or substitution of the 5 nucleotides. DNase I footprint analysis revealed that purified IcaR, thought to be a regulator of ica transcription, also binds to the ica promoter sequence just upstream of the ica start codon, but its affinity for the ica promoter is unaffected by deletion of the 5‐nucleotide motif. These findings identify a 5‐nucleotide motif within the ica promoter region that has a functional role in transcriptional regulation of the ica locus that is independent of IcaR, and also show that IcaR binds to the promoter region of the S. aureus ica locus.