bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modern analytical ultracentrifugation in protein science: A tutorial review
Authors: Lebowitz Jacob , Lewis Marc S. , Schuck Peter 
Published: October 2002

AbstractAnalytical ultracentrifugation (AU) is reemerging as a versatile tool for the study of proteins. Monitoring the sedimentation of macromolecules in the centrifugal field allows their hydrodynamic and thermodynamic characterization in solution, without interaction with any matrix or surface. The combination of new instrumentation and powerful computational software for data analysis has led to major advances in the characterization of proteins and protein complexes. The pace of new advancements makes it difficult for protein scientists to gain sufficient expertise to apply modern AU to their research problems. To address this problem, this review builds from the basic concepts to advanced approaches for the characterization of protein systems, and key computational and internet resources are provided. We will first explore the characterization of proteins by sedimentation velocity (SV). Determination of sedimentation coefficients allows for the modeling of the hydrodynamic shape of proteins and protein complexes. The computational treatment of SV data to resolve sedimenting components has been achieved. Hence, SV can be very useful in the identification of the oligomeric state and the stoichiometry of heterogeneous interactions. The second major part of the review covers sedimentation equilibrium (SE) of proteins, including membrane proteins and glycoproteins. This is the method of choice for molar mass determinations and the study of self‐association and heterogeneous interactions, such as protein–protein, protein–nucleic acid, and protein–small molecule binding.
Unfolding of the loggerhead sea turtle (Caretta caretta) myoglobin: A 1H‐NMR and electronic absorbance study
Authors: Castelli Daniela Delli , Lovera Elena , Ascenzi Paolo , Fasano Mauro 
Published: October 2002

AbstractThe effect of urea concentration on the backbone solution structure of the cyanide derivative of ferric Caretta caretta myoglobin (at pH 5.4) is reported. By addition of urea, sequential and long‐range nuclear Overhauser effects (NOEs) are gradually lost. By using the residual NOE constraints to build the molecular model, a picture of the unfolding pathway was obtained. When the urea concentration is raised to 2.2 M, helices A and B appear largely disordered; helices C, D, and F loose structural constraints at 3.0 M urea. At urea concentration >6 M, the protein appears to be fully unfolded, including the GH hairpin and helix E stabilizing the prosthetic group. Reversible and cooperative denaturation isotherms obtained by following NOE peaks are considerably different from those obtained by monitoring electronic absorption changes. The reversible and cooperative urea‐dependent folding‐unfolding process of C. caretta myoglobin follows the minimum three‐state mechanism N⟷X⟷D, where X represents a disordered globin structure (occurring at ∼4 M urea) that still binds the heme.
Osmolyte effects on helix formation in peptides and the stability of coiled‐coils
Authors: Celinski Scott A. , Scholtz J. Martin 
Published: October 2002

AbstractThe ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine‐based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine‐N‐oxide (TMAO) is the best structure‐inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE). We also provide a semiquantitative study of the ability of TMAO to induce helix formation and urea, which acts as a helix (and protein) denaturant. We find that on a molar basis, these agents are exactly counteractive as structure inducing and unfolding agents. Finally, we extend the investigations to the effects of urea and TMAO on the stability of a dimeric coiled‐coil peptide and find identical results. Together these results support the tenets of the osmophobic hypothesis and highlight the importance of the polypeptide backbone in protein folding and stability.
Interatomic potentials and solvation parameters from protein engineering data for buried residues
Authors: Lomize Andrei L. , Reibarkh Mikhail Y. , Pogozheva Irina D. 
Published: October 2002

AbstractVan der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (H‐bonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of free‐energy differences. The set of mutants included substitutions of uncharged, inflexible, water‐inaccessible residues in α‐helices and β‐sheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and H‐bonds were smaller than in molecular mechanics and followed the “like dissolves like” rule, as expected in condensed media but not in vacuum. The depths of modified Lennard‐Jones potentials were −0.34, −0.12, and −0.06 kcal/mole for similar atom types (polar–polar, aromatic–aromatic, and aliphatic–aliphatic interactions, respectively) and −0.10, −0.08, −0.06, −0.02, and nearly 0 kcal/mole for different types (sulfur–polar, sulfur–aromatic, sulfur–aliphatic, aliphatic–aromatic, and carbon–polar, respectively), whereas the depths of H‐bond potentials were −1.5 to −1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, −1, −21, and −66 cal/moleÅ2 for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the water–protein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.
Crucial stages of protein folding through a solvable model: Predicting target sites for enzyme‐inhibiting drugs
Authors: Micheletti Cristian , Cecconi Fabio , Flammini Alessandro , Maritan Amos 
Published: October 2002

AbstractAn exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key sites for the folding of human immunodeficiency virus type 1 (HIV‐1) protease. The predicted sites are found to correlate well with clinical data on resistance to Food and Drug Administration‐approved drugs. It has been observed that the effects of drug therapy are to induce multiple mutations on the protease. The sites where such mutations occur correlate well with those involved in folding bottlenecks identified through the deterministic procedure proposed in this study. The high statistical significance of the observed correlations suggests that the approach may be promisingly used in conjunction with traditional techniques to identify candidate locations for drug attacks.
Spectral Synthesis and Masa‐Bimodules
Authors: Todorov I. G. 
Published: October 2002

The interaction between harmonic analysis and operator theory has been fruitful. In [1] Arveson related results in the theory of operator algebras to spectral synthesis. He defined synthesis for subspace lattices and proved that certain classes of lattices are synthetic. The main result in this paper is a generalization of a result of Arveson for the case of subspace maps. In order to describe in more detail the content of the present work, we need to introduce some definitions and facts from [2] and [9].Let H1 and H2 be separable complex Hilbert spaces, and Pi be the lattice of all (orthogonal) projections on Hi, i = 1, 2. Following Erdos [1], we let M(P1, P2) denote the set of all maps φ : P1 → P2 which are 0‐preserving and v‐continuous (that is, they preserve arbitrary suprema). We will call such maps subspace maps. It was shown in [2] that each φ ∈ M(P1, P2) uniquely defines semi‐lattices S1φ ⊆ P1 and S2φ = φ(P1) ⊆ P2 such that φ is a bijection between S1φ and S2φ and is uniquely determined by its restriction to S1φ. Moreover, S1φ is meet‐complete and contains the identity projection while S2φ is join‐complete and contains the zero projection. If S1φ and S2φ are commutative, we say that φ is a commutative subspace map.
Sharp Weighted Estimates for Multilinear Commutators
Authors: Pérez C. , Trujillo-González R. 
Published: October 2002

Multilinear commutators with vector symbol =(b1,…,bm) defined by are considered, where K is a Calderón–Zygmund kernel. The following a priori estimates are proved for w ∈ A∞. For 0 < p < ∞, there exists a constant C such that and where

and ML(log L)α is an Orlicz type maximal operator. This extends, with a different approach, classical results by Coifman.As a corollary, it is deduced that the operators are bounded on Lp(w) when w ∈ Ap, and that they satisfy corresponding weighted L(log L)1/r‐type estimates with w ∈ A1.
Schemes of Line Modules I
Authors: Shelton Brad , Vancliff Michaela 
Published: October 2002

It is proved that there exists a scheme that represents the functor of line modules over a graded algebra, and it is called the line scheme of the algebra. Its properties and its relationship to the point scheme are studied. If the line scheme of a quadratic, Auslander‐regular algebra of global dimension 4 has dimension 1, then it determines the defining relations of the algebra.Moreover, the following counter‐intuitive result is proved. If the zero locus of the defining relations of a quadratic (not necessarily regular) algebra on four generators with six defining relations is finite, then it determines the defining relations of the algebra. Although this result is non‐commutative in nature, its proof uses only commutative theory.The structure of the line scheme and the point scheme of a 4‐dimensional regular algebra is also used to determine basic incidence relations between line modules and point modules.
Origin of the Biomechanical Properties of Wood Related to the Fine
Structure of the Multi-layered Cell Wall
Authors: Yamamoto H. , Kojima Y. , Okuyama T. , Abasolo W. P. , Gril J. 
Published: October 2002

Abstract
In this study, a basic model is introduced to describe the biomechanical properties of the wood from the viewpoint of the composite structure of its cell wall. First, the mechanical interaction between the cellulose microfibril (CMF) as a bundle framework and the lignin-hemicellulose as a matrix (MT) skeleton in the secondary wall is formulated based on “the two phase approximation.” Thereafter, the origins of (1) tree growth stress, (2) shrinkage or swelling anisotropy of the wood, and (3) moisture dependency of the Young’s modulus of wood along the grain were simulated using the newly introduced model. Through the model formulation; (1) the behavior of the cellulose microfibril (CMF) and the matrix substance (MT) during cell wall maturation was estimated; (2) the moisture reactivity of each cell wall constituent was investigated; and (3) a realistic model of the fine composite structure of the matured cell wall was proposed. Thus, it is expected that the fine structure and internal property of each cell wall constituent can be estimated through the analyses of the macroscopic behaviors of wood based on the two phase approximation.
A New In Vitro Model to Evaluate Differential
Responses of Endothelial Cells to Simulated Arterial Shear Stress Waveforms
Authors: Blackman Brett R. , García-Cardeña Guillermo , Gimbrone Michael A. 
Published: October 2002

Abstract
In the circulation, flow-responsive endothelial cells (ECs) lining the lumen of blood vessels are continuously exposed to complex hemodynamic forces. To increase our understanding of EC response to these dynamic shearing forces, a novel in vitro flow model was developed to simulate pulsatile shear stress waveforms encountered by the endothelium in the arterial circulation. A modified waveform modeled after flow patterns in the human abdominal aorta was used to evaluate the biological responsiveness of human umbilical vein ECs to this new type of stimulus. Arterial pulsatile flow for 24 hours was compared to an equivalent time-average steady laminar shear stress, using no flow (static) culture conditions as a baseline. While both flow stimuli induced comparable changes in cell shape and alignment, distinct patterns of responses were observed in the distribution of actin stress fibers and vinculin-associated adhesion complexes, intrinsic migratory characteristics, and the expression of eNOS mRNA and protein. These results thus reveal a unique responsiveness of ECs to an arterial waveform and begin to elucidate the complex sensing capabilities of the endothelium to the dynamic characteristics of flows throughout the human vascular tree.
Unsteady and Three-Dimensional Simulation of Blood Flow in the Human
Aortic Arch
Authors: Shahcheraghi N. , Dwyer H. A. , Cheer A. Y. , Barakat A. I. , Rutaganira T. 
Published: October 2002

Abstract
A three-dimensional and pulsatile blood flow in a human aortic arch and its three major branches has been studied numerically for a peak Reynolds number of 2500 and a frequency (or Womersley) parameter of 10. The simulation geometry was derived from the three-dimensional reconstruction of a series of two-dimensional slices obtained in vivo using CAT scan imaging on a human aorta. The numerical simulations were obtained using a projection method, and a finite-volume formulation of the Navier-Stokes equations was used on a system of overset grids. Our results demonstrate that the primary flow velocity is skewed towards the inner aortic wall in the ascending aorta, but this skewness shifts to the outer wall in the descending thoracic aorta. Within the arch branches, the flow velocities were skewed to the distal walls with flow reversal along the proximal walls. Extensive secondary flow motion was observed in the aorta, and the structure of these secondary flows was influenced considerably by the presence of the branches. Within the aorta, wall shear stresses were highly dynamic, but were generally high along the outer wall in the vicinity of the branches and low along the inner wall, particularly in the descending thoracic aorta. Within the branches, the shear stresses were considerably higher along the distal walls than along the proximal walls. Wall pressure was low along the inner aortic wall and high around the branches and along the outer wall in the ascending thoracic aorta. Comparison of our numerical results with the localization of early atherosclerotic lesions broadly suggests preferential development of these lesions in regions of extrema (either maxima or minima) in wall shear stress and pressure.
Competing Effects of Buckling and Anchorage Strength on Optimal Wheat
Stalk Geometry
Authors: Farquhar Tony , Zhou Jiang , Wood William H. 
Published: October 2002

Abstract
We seek the ideal wheat stalk, which minimizes the structural mass required to support a fixed grain load in the presence of gravity and wind. The optimization search is restricted to stepped cylindrical stems of known moduli and density but unknown dimension. Stem buckling and root anchorage strength are assumed to place restrictions on the permissible stalk resonant frequency in the presence of a specified wind forcing frequency. These effects are described mathematically, and the penalty parameter method is used to find stem mass minima for various stalk heights. In general, there are two alternative solution branches. The lower solution is the global minimum but it is probably impractical for field crops exposed to natural wind. The upper minimum is more conservative and therefore requires more stem mass. Due to the competing requirements of buckling versus anchorage strength, the parameter study shows that optimal wheat stem geometry has a nonlinear dependence on the intensity of gravity and the frequency spectra of the wind.
N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity
Authors: Hackbarth Corinne J. , Chen Dawn Z. , Lewis Jason G. , Clark Kirk , Mangold James B. , Cramer Jeffrey A. , Margolis Peter S. , Wang Wen , Koehn Jim , Wu Charlotte , Lopez S. , Withers George , Gu Helen , Dunn Elina , Kulathila R. , Pan Shi-Hao , Porter Wilma L. , Jacobs Jeff , Trias Joaquim , Patel Dinesh V. , Weidmann Beat , White Richard J. , Yuan Zhengyu 
Published: October 2002

ABSTRACTPeptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1′ site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors withN-alkyl urea at the P1′ site. Compounds with MICs of ≤4 μg/ml against gram-positive and gram-negative pathogens, includingStaphylococcusaureus,Streptococcuspneumoniae, andHaemophilusinfluenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) forEscherichiacoliNi-PDF were ≤0.1 μM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 μM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 Å. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. TheseN-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.
Different Levels of Genetic Homogeneity in Vancomycin-Resistant and -Susceptible
Enterococcus faecium
Isolates from Different Human and Animal Sources Analyzed by Amplified-Fragment Length Polymorphism
Authors: Bruinsma Nienke , Willems Rob J. L. , van den Bogaard Anthony E. , van Santen-Verheuvel Marga , London Nancy , Driessen Christel , Stobberingh Ellen E. 
Published: October 2002

ABSTRACT

The genetic relationship among fecal vancomycin-resistant
Enterococcus faecium
(VREF) and vancomycin-susceptible
E. faecium
(VSEF) isolates (
n
= 178) from the same populations of pigs, human healthy volunteers, and hospitalized patients (from The Netherlands) and chickens (from The Netherlands and Greece) was studied by amplified-fragment length polymorphism (AFLP). The majority of VREF isolates from pigs, healthy volunteers, and hospitalized patients grouped together (genetic similarity, ≥65%). In a previous AFLP study by our group the VREF isolates from hospitalized patients grouped separately, most likely because these were clinical and not fecal isolates as in the present study. Furthermore, VSEF isolates from humans and pigs were found much more genetically diverse than VREF isolates, whereas VREF and VSEF isolates from chickens clustered together in a separate genogroup (genetic similarity, ≥65%), a pattern clearly distinct from the patterns for human and pig isolates. The present study suggests that pigs are a more important source of VREF for humans than chickens and that human- and pig-derived VSEF isolates seem much more heterogeneous than VREF isolates.
The LisRK Signal Transduction System Determines the Sensitivity of
Listeria monocytogenes
to Nisin and Cephalosporins
Authors: Cotter Paul D. , Guinane Caitriona M. , Hill Colin 
Published: October 2002

ABSTRACT

The
Listeria monocytogenes
two-component signal transduction system, LisRK, initially identified in strain LO28, plays a significant role in the virulence potential of this important food-borne pathogen. Here, it is shown that, in addition to its major contribution in responding to ethanol, pH, and hydrogen peroxide stresses, LisRK is involved in the ability of the cell to tolerate important antimicrobials used in food and in medicine, e.g., the lantibiotic nisin and the cephalosporin family of antibiotics. A Δ
lisK
mutant (lacking the LisK histidine kinase sensor component) displays significantly enhanced resistance to the lantibiotic nisin, a greatly enhanced sensitivity to the cephalosporins, and a large reduction in the expression of three genes thought to encode a penicillin-binding protein, another histidine kinase (other than LisK), and a protein of unknown function. Confirmation of the role of LisRK was obtained when the response regulator, LisR, was overexpressed using both constitutive and inducible (nisin-controlled expression) systems. Under these conditions we observed a reversion of the Δ
lisK
mutant to wild-type growth kinetics in the presence of nisin. It was also found that overexpression of LisR complemented the reduced expression of two of the aforementioned genes. These results demonstrate the important role of LisRK in the response of
L. monocytogenes
to a number of antimicrobial agents.
Frequency of Disinfectant Resistance Genes and Genetic Linkage with β-Lactamase Transposon Tn552among Clinical Staphylococci
Authors: Sidhu Maan Singh , Heir Even , Leegaard Truls , Wiger Karianne , Holck Askild 
Published: October 2002

ABSTRACTA total of 61 strains ofStaphylococcus aureusand 177 coagulase-negative staphylococcal strains were isolated from the blood of patients with bloodstream infections and from the skin of both children under cancer treatment and human immunodeficiency virus-positive patients. The MIC analyses revealed that 118 isolates (50%) were resistant to quaternary ammonium compound-based disinfectant benzalkonium chloride (BC). The frequencies of resistance to a range of antibiotics were significantly higher among BC-resistant staphylococci than among BC-sensitive staphylococci. Of 78 BC-resistant staphylococcal isolates, plasmid DNA from 65 (83%), 2 (3%), 43 (55%), and 15 (19%) isolates hybridized toqacAor -B(qacA/B),qacC,blaZ, andtetKprobes, respectively. TheqacA/BandblaZprobes hybridized to the same plasmid in 19 (24%) staphylococcal strains. The plasmids harboring bothqacA/BandblaZgenes varied from approximately 20 to 40 kb. TheStaphylococcus epidermidisFol62 isolate, harboring multiresistance plasmid pMS62, containedqacA/BandblaZtogether withtetK. Molecular and genetic studies indicated different structural arrangements ofblaZandqacA/B, including variable intergenic distances and transcriptional directions of the two genes on the same plasmid within the strains. The different organizations may be due to the presence of various genetic elements involved in cointegration, recombination, and rearrangements. These results indicate thatqacresistance genes are common and that linkage between resistance to disinfectants and penicillin resistance occurs frequently in clinical isolates in Norway. Moreover, the higher frequency of antibiotic resistance among BC-resistant strains indicates that the presence of either resistance determinant selects for the other during antimicrobial therapy and disinfection in hospitals.