bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of monomeric Cro variants: Isoenergetic transformation of a type I′ to a type II′ β‐hairpin by single amino acid replacements
Authors: Mollah A.K.M.M. , Stennis Rhonda L. , Mossing Michael C.
Published: April 2003

The thermodynamic stabilities of three monomeric variants of the bacteriophage λ Cro repressor that differ only in the sequence of two amino acids at the apex of an engineered β‐hairpin have been determined. The sequences of the turns are EVK‐XX‐EVK, where the two central residues are DG, GG, and GT, respectively. Standard‐state unfolding free energies, determined from circular dichroism measurements as a function of urea concentration, range from 2.4 to 2.7 kcal/mole, while those determined from guanidine hydrochloride range from 2.8 to 3.3 kcal/mole for the three proteins. Thermal denaturation yields van't Hoff unfolding enthalpies of 36 to 40 kcal /mole at midpoint temperatures in the range of 53 to 58°C. Extrapolation of the thermal denaturation free energies with heat capacities of 400 to 600 cal/mole deg gives good agreement with the parameters determined in denaturant titrations. As predicted from statistical surveys of amino acid replacements in β‐hairpins, energetic barriers to transformation from a type I′ turn (DG) to a type II′ turn (GT) can be quite small.
A novel member of the split βαβ fold: Solution structure of the hypothetical protein YML108W from Saccharomyces cerevisiae
Authors: Pineda‐Lucena Antonio , Liao Jack C.C. , Cort John R. , Yee Adelinda , Kennedy Michael A. , Edwards Aled. M. , Arrowsmith Cheryl H.
Published: April 2003

As part of the Northeast Structural Genomics Consortium pilot project focused on small eukaryotic proteins and protein domains, we have determined the NMR structure of the protein encoded by ORF YML108W from Saccharomyces cerevisiae. YML108W belongs to one of the numerous structural proteomics targets whose biological function is unknown. Moreover, this protein does not have sequence similarity to any other protein. The NMR structure of YML108W consists of a four‐stranded β‐sheet with strand order 2143 and two α‐helices, with an overall topology of ββαββα. Strand β1 runs parallel to β4, and β2:β1 and β4:β3 pairs are arranged in an antiparallel fashion. Although this fold belongs to the split βαβ family, it appears to be unique among this family; it is a novel arrangement of secondary structure, thereby expanding the universe of protein folds.
Mutations in domain a′ of protein disulfide isomerase affect the folding pathway of bovine pancreatic ribonuclease A
Authors: Ruoppolo Margherita , Orrù Stefania , Talamo Fabio , Ljung Johanna , Pirneskoski Annamari , Kivirikko Kari I. , Marino Gennaro , Koivunen Peppi
Published: April 2003

Protein disulfide isomerase (PDI, EC 5.3.4.1), an enzyme and chaperone, catalyses disulfide bond formation and rearrangements in protein folding. It is also a subunit in two proteins, the enzyme collagen prolyl 4‐hydroxylase and the microsomal triglyceride transfer protein. It consists of two catalytically active domains, a and a′, and two inactive ones, b and b′, all four domains having the thioredoxin fold. Domain b′ contains the primary peptide binding site, but a′ is also critical for several of the major PDI functions. Mass spectrometry was used here to follow the folding pathway of bovine pancreatic ribonuclease A (RNase A) in the presence of three PDI mutants, F449R, Δ455–457, and abb′, and the individual domains a and a′. The first two mutants contained alterations in the last α helix of domain a′, while the third lacked the entire domain a′. All mutants produced genuine, correctly folded RNase A, but the appearance rate of 50% of the product, as compared to wild‐type PDI, was reduced 2.5‐fold in the case of PDI Δ455–457, 7.5‐fold to eightfold in the cases of PDI F449R and PDI abb′, and over 15‐fold in the cases of the individual domains a and a′. In addition, PDI F449R and PDI abb′ affected the distribution of folding intermediates. Domains a and a′ catalyzed the early steps in the folding but no disulfide rearrangements, and therefore the rate observed in the presence of these individual domains was similar to that of the spontaneous process.
Heat Transfer Enhancement Using a Convex-Patterned Surface
Authors: Moon H. K. , O’Connell T. , Sharma R.
Published: April 2003

The heat transfer rate from a smooth wall in an internal cooling passage can be significantly enhanced by using a convex patterned surface on the opposite wall of the passage. This design is particularly effective for a design that requires the heat transfer surface to be free of any augmenting features (smooth). Heat transfer coefficients on the smooth wall in a rectangular channel, which had convexities on the opposite wall were experimentally investigated. Friction factors were also measured to assess the thermal performance. Relative clearances δ/d between the convexities and the smooth wall of 0, 0.024, and 0.055 were investigated in a Reynolds number ReHD range from 15,000 to 35,000. The heat transfer coefficients were measured in the thermally developed region using a transient thermochromic liquid crystal technique. The clearance gap between the convexities and the smooth wall adversely affected the heat transfer enhancement NuHD. The friction factors (f ), measured in the aerodynamically developed region, were largest for the cases of no clearance δ/d=0). The average heat transfer enhancement Nu¯HD was also largest for the cases of no clearance δ/d=0, as high as 3.08 times at a Reynolds number of 11,456 in relative to that Nuo of an entirely smooth channel. The normalized Nusselt numbers Nu¯HD/Nuo, as well as the normalized friction factors f/fo, for all three cases, decreased with Reynolds numbers. However, the decay rate of the friction factor ratios f/fo with Reynolds numbers was lower than that of the normalized Nusselt numbers. For all three cases investigated, the thermal performance Nu¯HD/Nuo/f/fo1/3 values were within 5% to each other. The heat transfer enhancement using a convex patterned surface was thermally more effective at a relative low Reynolds numbers (less than 20,000 for δ/d=0) than that of a smooth channel.
Casting Metal Nanowires Within Discrete Self-Assembled Peptide Nanotubes
Authors: Reches Meital , Gazit Ehud
Published: April 2003

Tubular nanostructures are suggested to have a wide range of applications in nanotechnology. We report our observation of the self-assembly of a very short peptide, the Alzheimer's β-amyloid diphenylalanine structural motif, into discrete and stiff nanotubes. Reduction of ionic silver within the nanotubes, followed by enzymatic degradation of the peptide backbone, resulted in the production of discrete nanowires with a long persistence length. The same dipeptide building block, made of D-phenylalanine, resulted in the production of enzymatically stable nanotubes.
All-Metal Antiaromatic Molecule: Rectangular Al
4
4-
in the Li
3
Al
4
-
Anion
Authors: Kuznetsov Aleksey E. , Birch K. Alexander , Boldyrev Alexander I. , Li Xi , Zhai Hua-Jin , Wang Lai-Sheng
Published: April 2003

We report the experimental and theoretical characterization of antiaromaticity in an all-metal system, Li
3
Al
4
–
, which we produced by laser vaporization and studied with the use of photoelectron spectroscopy and ab initio calculations. The most stable structure of Li
3
Al
4
–
found theoretically contained a rectangular Al
4
4–
tetraanion stabilized by the three Li
+
ions in a capped octahedral arrangement. Molecular orbital analyses reveal that the rectangular Al
4
4–
tetraanion has four π electrons, consistent with the 4
n
Hückel rule for antiaromaticity.
Absolute Asymmetric Synthesis: A Commentary
Authors: Mislow Kurt
Published: April 2003

Absolute asymmetric synthesis,i.e., the formation of enantiomerically enriched products from achiral precursors without the intervention of chiral chemical reagents or catalysts, is in practice unavoidable on statistical grounds alone. That random chance, combined with suitable amplification mechanisms, might ultimately account for biomolecular homochirality in Nature was recognized more than a century ago. Soai and collaborators have recently developed an asymmetric autocatalysis reaction that is capable of amplifying a tiny enantiomeric excess of far below 1% to yield a nearly enantiopure product. Although there is no easy way to tell the difference between an asymmetric autocatalysis reaction initiated by the tiny enantiomeric excess due to random chance and one initiated by minuscule quantities of unidentified chiral impurities, it is nevertheless all but certain that the Soai reaction is capable of producing optically active compounds by an absolute asymmetric synthesis, starting from nominally achiral reagents free of chiral contaminants and run under achiral conditions,e.g., without the intervention of chiral physical forces.
Diastereoselective Addition of α-Metalated Sulfoxides to Imines Revisited: Mechanism, Computational Studies, and the Effect of External Chiral Ligands
Authors: Pedersen Brian , Rein Tobias , Søtofte Inger , Norrby Per-Ola , Tanner David
Published: April 2003

Some new results on asymmetric synthesis via the addition of α-metalated methyl tolyl sulfoxides to imines are presented. Good diastereoselectivity (up to >98% d.e. for product 3g) can be obtained under conditions of kinetic control (short reaction time, low temperature). The transition state (a six-membered "flat chair") was probed by quantum mechanical calculations, which underpinned the idea of using external chiral ligands to enhance the diastereoselectivity of otherwise moderately selective reactions. In this way, the diastereomeric ratio of the product 3a could be raised from (84:16) to (>99:1) by use of a readily available C2-symmetric bis(sulfonamide) ligand.
Synthesis of 2-Hydroxy-8'-(hydroxymethyl)-1,1'-binaphthalene (iso-Homo-BINOL). A New Structural Pattern in the Binaphthyl Realm
Authors: Vyskočil Štěpán , Lockhart Stephen C. , Mitchell William L. , Kočovský Pavel
Published: April 2003

The title compound 7 has been synthesized in a racemic form, using Suzuki coupling (8 + 15 → 16) as the key step. Pure enantiomer (S)-(-)-7 has been obtained by carbonylation of the known bromide (S)-(+)-12 followed by reduction of the resulting methyl ester (S)-(+)-18 with LiAlH4.
On the Conformation of Glycobilirubin
Authors: Boiadjiev Stefan E. , Lightner David A.
Published: April 2003

The first optically active glycine conjugate1of a bilirubin was prepared in several steps from (S)-β-methylxanthobilirubic acid glycine conjugate8. The latter was synthesized by reaction of benzyl glycinate tosylate with the mixed anhydride formed in the reaction of (S)-β-methylxanthobilirubic acid6with isobutyl chloroformate. Spectroscopic analysis of the circular dichroism spectra of1in various solvents, including aqueous buffer, indicate a conformational preference for theM-helical ridge-tile conformation, thus providing the first spectroscopic evidence on the conformation of glycobilirubins.
SPEEDUP OF THE n-PROCESS MUTUAL EXCLUSION ALGORITHM
Authors: IGARASHI YOSHIHIDE , NISHITANI YASUAKI
Published: April 2003

We propose two modifications of the n-process mutual exclusion algorithm by Peterson for the asynchronous multi-writer/reader shared memory model. By any of the modifications we can speed up the original n-process algorithm. The running times for the trying regions of the first modified algorithm and the second modified algorithm are (2n - 3)c + O(n3 l) and (n - 1)c + O(n3 l), respectively, where n is the number of processes, l is an upper bound on the time between two steps, and c is an upper bound on the time that any user spends in the critical region. These running times are improvements on the running time, O(n2c + n4 l) of the original n-process algorithm for the same asynchronous shared memory model.
SMALL RECOIL APPROXIMATION
Authors: LAM C. S.
Published: April 2003

In this review we discuss a technique to compute and to sum a class of Feynman diagrams, and some of its applications. These are diagrams containing one or more energetic particles that suffer very little recoil in their interactions. When recoil is completely neglected, a decomposition formula can be proven. This formula is a generalization of the well-known eikonal formula, to non-Abelian interactions. It expresses the amplitude as a sum of products of the irreducible amplitudes, with each irreducible amplitude being the amplitude to emit one, or several mutually interacting, quasiparticles. For Abelian interaction a quasiparticle is nothing but the original boson, so this decomposition formula reduces to the eikonal formula. In non-Abelian situations each quasiparticle can be made up of many bosons, though always with a total quantum number identical to that of a single boson. This decomposition enables certain amplitudes of all orders to be summed up into an exponential form, and it allows subleading contributions of a certain kind, which is difficult to reach in the usual way, to be computed. For bosonic emissions from a heavy source with many constituents, a quasiparticle amplitude turns out to be an amplitude in which all bosons are emitted from the same constituent. For high-energy parton-parton scattering in the near-forward direction, the quasiparticle turns out to be the Reggeon, and this formalism shows clearly why gluons reggeize but photons do not. The ability to compute subleading terms in this formalism allows the BFKL–Pomeron amplitude to be extrapolated to asymptotic energies, in a unitary way preserving the Froissart bound. We also consider recoil corrections for Abelian interactions in order to accommodate the Landau–Pomeranchuk–Migdal effect.
ELECTRON STANDING WAVES AT A SURFACE DURING REFLECTION HIGH ENERGY ELECTRON DIFFRACTION AND APPLICATION TO STRUCTURE ANALYSIS
Authors: YAMANAKA TOSHIRO , INO SHOZO
Published: April 2003

During observation of reflection high energy electron diffraction (RHEED), the interference between the incident and diffracted beams leads to the formation of surface electron standing waves. Characteristic X-ray emission is strongly excited if the atom exists in a strong wave field. Therefore, X-ray yields depends on the position of the atom and incident glancing angle (θg) of the electron beam, since the distribution of these waves changes with θg. Such anomalous intensities of X-ray emission are clearly observed under both Bragg and surface wave resonance conditions. By using these intensities, the height and adsorption site of surface adatoms can be analyzed. In this review, surface electron channeling and its application to surface structure analysis are discussed.
RECENT DEVELOPMENTS IN ALKALI METAL INTERCALATION OF LAYERED TRANSITION METAL DICHALCOGENIDES
Authors: STARNBERG H. I.
Published: April 2003

The modification of layered transition metal dichalcogenides through intercalation is reviewed, with special emphasis on in situ intercalation with alkali metals. Experimental results obtained using photoelectron spectroscopy, low-energy electron diffraction, scanning tunneling microscopy and transmission electron microscopy are presented, and conclusions about the in situ intercalation process and the associated crystallographic and electronic structure changes are presented. It is stressed that various kinds of defects and disorders must be taken into account for a full understanding.
MIXED STATE ANALYSIS OF MULTIVARIATE TIME SERIES
Authors: WIESENFELDT MARTIN , PARLITZ ULRICH , LAUTERBORN WERNER
Published: April 2003

A method is presented for detecting weak coupling between (chaotic) dynamical systems below the threshold of (generalized) synchronization. This approach is based on reconstruction of mixed states consisting of delayed samples taken from simultaneously measured time series of both systems.
CHAOTIC SOLUTION OF THE rf-DRIVEN JOSEPHSON SYSTEM WITH QUADRATIC DAMPING
Authors: HAI WENHUA , ZHANG XILI , HUANG WEILI , CHONG GUISHU
Published: April 2003

The method of direct perturbation is applied to a rf-driven Josephson junction with strong and quadratic damping resistor. Perturbed correction to the heteroclinic orbit is constructed and its boundedness conditions are established to contain the Melnikov criterion for the onset of chaos. The result shows that the corrected heteroclinic orbit is unbounded, unless it is chaotic. The analytically deterministic chaotic solution exposes the incomputability of chaotic orbits, which is numerically demonstrated.
Development of Chronic Myelocytic Leukemia after Chemotherapy for Malignant Fibrous Histiocytoma
Authors: Yamamura Ryousuke , Yamane Takahisa , Aoyama Yasutaka , Nakamae Hirohisa , Makita Kaori , Shima Etsuko , Ohta Kensuke , Inoue Takeshi , Sakamoto Hirokazu , Hino Masayuki
Published: April 2003

At the age of 28, a 33-year-old male was diagnosed with malignant fibrous histiocytoma (MFH) with a primary lesion in the right maxillary sinus. Although arterial infusion chemotherapy (pirarubicin hydrochloride and carboplatin) was given, no tumor shrinkage was observed, and surgery was therefore performed to remove the tumor. Thereafter, the patient received autologous peripheral blood stem cell transplantation with high-dose chemotherapy (combination of ifosphamide, carboplatin and etoposide) as pretreatment. An increase in the peripheral leukocyte count was noted 56 months after the diagnosis of MFH was made. Cytogenetic study showed translocation (9;22)(q34;q11). Chronic myelocytic leukemia (CML) was therefore diagnosed. MFH was in a state of complete remission. The clinical course of this patient strongly suggests that this was a case of treatment-related CML that developed after chemotherapy for MFH. Treatment-related malignant blood diseases are known to include acute myelocytic leukemia and myelodysplastic syndrome, but reports of treatment-related CML are rare, although there have been some cases of treatment-related CML occurring several years after pretreatment.
Thyroid Hormone Receptor-Specific Interactions with Steroid Receptor Coactivator-1 in the Pituitary
Authors: Sadow Peter M. , Koo Eugene , Chassande Olivier , Gauthier Karine , Samarut Jacques , Xu Jianming , O’Malley Bert W. , Seo Hisao , Murata Yoshiharu , Weiss Roy E.
Published: April 2003

Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) as well as other nuclear receptors. However, it is not known whether the SRC-1-mediated activation of TH-regulated gene transcription is TR isoform specific in the pituitary. We generated mice that were deficient in TRα and SRC-1 (TRα0/0SRC-1−/−), as well in TRβ and SRC-1 (TRβ−/−SRC-1−/−), and thyroid function tests and effects of TH deprivation and TH treatment were compared with wild-type mice or mice with deletion of either TRs or SRC-1 alone. We have shown that 1) TRβ−/−SRC-1−/− mice demonstrate more severe TH resistance than either the SRC-1−/− or TRβ−/− mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRβ; 2) SRC-1 facilitates TRβ and TRα-mediated down-regulation of TSH, as TRα0/0SRC-1−/− mice demonstrate TH resistance rather than hypersensitivity as seen in TRα0/0mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRα-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes.
Surface pressure disturbance in the Ebro Valley (Spain) produced by the Pyrenees mountains during PYREX
Authors: Argandoña J. D'IAZ DE , Ezcurra A. , Bénech B.
Published: April 2003

In this paper, the pressure anomaly created by the Pyrenees during the Pyrenees Experiment (PYREX) in the Ebro Valley is studied and analysed. In the first part, pressure disturbance is obtained during some selected cases of PYREX by subtracting the synoptic component from the pressure registered by microbarographs and regular meteorological stations located in the area. As expected from a linear model, a low pressure is found for northerly synoptic winds and a high pressure for southerly synoptic winds. Data shows that the maximum pressure anomaly observed may reach values of the order of 7 hPa. Pressure‐anomaly spatial patterns found inside the valley are classified by using principal component analysis (PCA). It is found that the first axes deduced from the PCA carried out represent 75% of the variance in pressure data, indicating that all the stations analysed observed pressure anomalies in a correlated manner. Pressure anomalies are then related to incident‐air characteristics expressed as Froude and Rossby numbers. Significant correlation is generally found with these numbers in all cases, demonstrating the dynamic origin of the pressure anomaly computed. Copyright © 2007 Royal Meteorological Society
Palladium Nanotubes with Tailored Wall Morphologies
Authors: Steinhart M. , Jia Z. , Schaper A.K. , Wehrspohn R.B. , Gösele U. , Wendorff J.H.
Published: April 2003

Wetting of porous templates by multi‐component mixtures followed by demixing and controlled morphology ripening is a universal method to prepare nanotubes with tailored wall morphologies (see Figure). This is demonstrated here exemplarily by means of palladium nanotubes with a specific nano‐roughness and porosity.
Shear and Young's Moduli of MoS2 Nanotube Ropes
Authors: Kis A. , Mihailovic D. , Remskar M. , Mrzel A. , Jesih A. , Piwonski I. , Kulik A.J. , Benoît W. , Forró L.
Published: April 2003

The interaction between individual nanotubes in MoS2 bundles is investigated here using an atomic force microscope (AFM). Upon elastically deforming the ropes with the AFM, the value of the bending modulus of the MoS2 tube ensemble could be evaluated. This is turn could be used to obtain a lower estimate of the shear and Young's moduli of the nanotubes. The results indicate that the MoS2 ropes are highly anisotropic and that the interaction between the individual tubes comprising the rope is very weak.
Virus‐Based Alignment of Inorganic, Organic, and Biological Nanosized Materials
Authors: Lee S.‐W. , Lee S.K. , Belcher A.M.
Published: April 2003

A self‐ordering system based on anti‐streptavidin viruses is presented. A variety of materials, including inorganic nanoparticles, small organic molecules, and large biomolecules, can be organized at the nanometer length scale using this method. Molecular recognition is used to bind nanosize materials (e.g., gold nanoparticles) to the virus (see cover) and the resulting complex spontaneously evolves into a self‐supporting hybrid film (see Figure).
Fast pH‐thermo‐responsive copolymer hydrogels with micro‐porous structures
Authors: Kishi R. , Miura T. , Kihara H. , Asano T. , Shibata M. , Yosomiya R.
Published: April 2003

Micro‐porous copolymer hydrogels were prepared by γ‐ray irradiation of mixed solutions of N‐isopropylacrylamide (NIPAAm) and acrylic acid (AAc) above the lower critical solution temperature (LCST). From Cryo‐SEM observations, the gels were found to consist of three‐dimensional fibrous micro‐gels and micro‐pores. The copolymer gels swelled at temperatures below the LCST and shrunk at temperatures above it, and they showed rapid volume transitions on a time scale on the order of a minute when experiencing temperature changes between 10 and 40°C. The transition times for thermal shrinking were almost the same regardless of AAc composition, but the transition times for thermal swelling were increased with increasing AAc contents. The copolymer gels also showed rapid volume transitions with time constants on the order of an hour on experiencing pH changes between 2 and 12. The transition times for pH volume change at 10°C were within one hour, except for the gels containing only small amounts of AAc. On the other hand, the transition times for pH‐dependent volume change at 40°C were increased with increasing AAc content. The lower responsiveness of the transition results from an increase in hydrophobicity arising from the formation of inter‐ and intra‐molecular hydrogen bonds between the non‐ionized carboxylic acid groups and the amide groups. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 75–84, 2003
Synthesis and properties of graft copolymer of cellulose diacetate with poly(caprolactone monoacrylate)
Authors: Wang Dongshan , Xuan Yingnan , Huang Yong , Shen Jiarui
Published: April 2003

Cellulose diacetate grafting poly(caprolactone monoacrylate) copolymers (CDA‐g‐PCLA) were synthesized by a two‐step reaction of cellulose diacetate (CDA) with poly(caprolactone monoacrylate) (PCLA). The isocyanate‐terminated intermediate (NCOPCLA) was prepared and grafted onto cellulose diacetate chains. The results of the structure analysis indicated that PCLA was connected to CDA by chemical bonding. The flow temperature of graft copolymers was lower than that of the pure CDA and decreased with increasing the grafting percentage. Outdoor soil burial tests and active sludge tests indicated that the graft copolymers have good biodegradability in natural conditions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 85–90, 2003
Genomics and mapping of Teleostei (bony fish)
Authors: Clark Melody S.
Published: April 2003

Until recently, the Human Genome Project held centre stage in the press releases concerning sequencing programmes. However, in October 2001, it was announced that the Japanese puffer fish (Takifugu rubripes, Fugu) was the second vertebrate organism to be sequenced to draft quality. Briefly, the spotlight was on fish genomes. There are currently two other fish species undergoing intensive sequencing, the green spotted puffer fish (Tetraodon nigroviridis) and the zebrafish (Danio rerio). But this trio are, in many ways, atypical representations of the current state of fish genomic research. The aim of this brief review is to demonstrate the complexity of fish as a group of vertebrates and to publicize the ‘lesser‐known’ species, all of which have something to offer. Copyright © 2003 John Wiley & Sons, Ltd.
Determinants of the exclusion zone in dopaminergic amacrine cell mosaics
Authors: Raven Mary A. , Eglen Stephen J. , Ohab John J. , Reese Benjamin E.
Published: April 2003

A fundamental organizing feature of the retina is the presence of regularly spaced distributions of neurons, yet we have little knowledge of how this patterning emerges during development. Among these retinal mosaics, the spatial organization of the dopaminergic amacrine cells is unique: using nearest‐neighbor and Vornoi domain analysis, we found that the dopaminergic amacrine cells were neither randomly distributed, nor did they achieve the regularity documented for other retinal cell types. Autocorrelation analysis revealed the presence of an exclusion zone surrounding individual dopaminergic amacrine cells and modeling studies confirmed this organization, as the mosaic could be simulated by a minimal distance spacing rule defined by a broad set of parameters. Experimental studies determined the relative contributions of tangential dispersion, fate determination, and cell death in the establishment of this exclusion zone. Clonal boundary analysis and simulations of proximity‐driven movement discount tangential dispersion, while data from bcl‐2 overexpressing mice rule out feedback‐inhibitory fate‐deterministic accounts. Cell death, by contrast, appears to eliminate dopaminergic amacrine cells that are within close proximity, thereby establishing the exclusion zone surrounding individual cells and in turn creating their mosaic regularity. J. Comp. Neurol. 461:123–136, 2003. © 2003 Wiley‐Liss, Inc.
Cervicovaginal (Papanicolaou) smear findings in patients with malignant mixed Müllerian tumors
Authors: Casey Mary B. , Caudill Jill L. , Salomão Diva R.
Published: April 2003

Malignant mixed Müllerian tumor is a rare neoplasm that occurs most frequently in elderly patients. It is characterized by a mixture of malignant epithelial and sarcomatous components. Little has been published about Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors. We present our experience, with an emphasis on cytologic detail. Nine patients (median age, 65 yr) met our study criteria. All available smears and surgical specimens were reviewed. Four smears were positive for malignancy, with a sensitivity of 44% (3 adenocarcinoma, and 1 squamous‐cell carcinoma, small‐cell type). The results of our study showed that Papanicolaou smear findings pertaining to malignant mixed Müllerian tumors are seen in patients with advanced‐stage disease with involvement of the lower uterine segment or cervix. The usual finding is large numbers of high‐grade epithelial malignant cells in a necrotic background. The mesenchymal component rarely sheds cells visible on Papanicolaou smear. Diagn. Cytopathol. 2003;28:245–249. © 2003 Wiley‐Liss, Inc.
Synthesis of 3‐substituted pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidines and related fused thiazolo derivatives
Authors: Ahmed Essam Kh.
Published: April 2003

Convenient syntheses of 3‐substituted ethyl 4‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrid[4′,3′:4,5]thieno[2,3‐d]pyrimidine‐7‐carboxylates 3a, b, 6, 11–13, ethyl 3‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5 H‐pyrido[4′,3′:4,5]thieno[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8‐7H‐carboxylate (4), and ethyl 2‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5H‐pyrido[4′,3′:4,5]thieno[2, 3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8[7H]carboxylate (8) from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahythieno[2,3‐c]pyridine‐3,6‐dicarboxylate (1) are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:201–207, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10131
Impairment of individual finger movements in Parkinson's disease
Authors: Agostino Rocco , Currà Antonio , Giovannelli Morena , Modugno Nicola , Manfredi Mario , Berardelli Alfredo
Published: April 2003

By analyzing the kinematics of repetitive, constant‐amplitude, finger oppositions, we compared the impairment of individual and nonindividual finger movements in patients with Parkinson's disease. In one task, subjects tapped only the index finger against the thumb (individual oppositions); in the other task, they tapped all four fingers together against the thumb pad (nonindividual oppositions). We used an optoelectronic motion analysis system to record movements in three‐dimensional space and recorded three 5‐second trials for each task. We counted how many finger oppositions subjects performed during each trial and measured the duration and amplitude of the flexions and extensions. We also calculated the duration of the pauses after flexion and extension. We assessed the deterioration of motor performance in patients by investigating the changes in speed and amplitude with task completion. During both tasks, normal subjects and patients performed finger flexions faster than extensions, and they invariably paused longer after flexion than after extension. Patients performed individual and nonindividual finger movements slowly and with reduced amplitude. Patients were disproportionately slow during flexion and in switching from flexion to extension. Movement slowness increased as finger oppositions progressed but predominantly when patients had to move fingers individually. In conclusion, in patients with Parkinson's disease, the motor performance deteriorated with task completion more during individual than during nonindividual finger movements. Parkinson's disease, therefore, impairs individual finger movements more than gross hand movements. This distinction reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output. © 2003 Movement Disorder Society
Mirtazapine in essential tremor: A double‐blind, placebo‐controlled pilot study
Authors: Pahwa Rajesh , Lyons Kelly E.
Published: April 2003

We sought to determine whether mirtazapine is safe and well‐tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double‐blind, placebo‐controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire‐39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients. © 2003 Movement Disorder Society
Short‐term effect of a single levodopa dose on micturition disturbance in Parkinson's disease patients with the wearing‐off phenomenon
Authors: Uchiyama Tomoyuki , Sakakibara Ryuji , Hattori Takamichi , Yamanishi Tomonori
Published: April 2003

We investigated the short‐term effects of a single dose of levodopa (L‐dopa) on micturition function in PD patients with wearing‐off phenomenon. Eighteen PD patients who had median Hoehn and Yahr scores of 5 during the off phase and 3 during the on phase were recruited. We carried out urodynamic studies before and about 1 hour after the patients had taken 100 mg of L‐dopa with dopa‐decarboxylase inhibitor (DCI). After taking the L‐dopa/DCI, urinary urgency and urge incontinence aggravated, whereas voiding difficulty was alleviated in all 12 patients. When compared to the baseline assessment, urodynamic study results after taking 100 mg of L‐dopa/DCI showed aggravated detrusor hyperreflexia; decreased maximum bladder capacity (P = 0.006); an increased maximum Watts Factor value (P = 0.001), reflecting the detrusor power on voiding; an increased Abrams‐Griffiths number (P = 0.042), reflecting urethral obstruction on voiding; decreased residual urine volume (P = 0.025); and increased static urethral closure pressure (P = 0.012). One hundred milligrams of L‐dopa/DCI worsened detrusor hyperreflexia, producing worsened urinary urgency and urge incontinence during the storage (bladder‐filling) phase. It also increased detrusor contractility much more than it did urethral obstruction in the voiding phase, producing overall lessening of voiding difficulty and improving voiding efficiency in our PD patients with the wearing‐off phenomenon. © 2003 Movement Disorder Society
How the no‐cloning theorem got its name
Authors: Peres A.
Published: April 2003

I was the referee who approved the publication of Nick Herbert's FLASH paper, knowing perfectly well that it was wrong. I explain why my decision was the correct one, and I briefly review the progress to which it led.
Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxidants in rats
Authors: Upasani C. D. , Balaraman R.
Published: April 2003

The present study aims to investigate the protective effect of Spirulina on lead‐induced changes in the levels of lipid peroxidation and endogenous antioxidants in liver, lung, heart, kidney and brain of rats. Levels of elemental lead were also measured in the organs of rats in all experimental groups. In the liver, lung, heart and kidney of lead‐exposed animals, there was a signiﬁcant (p < 0.001) increase in the lipid peroxidation and a decrease in the levels of endogenous antioxidants. Although, Spirulina did not affect the deposition of lead in organs apart from the brain, simultaneous administration of Spirulina to lead exposed animals signiﬁcantly (p < 0.001) inhibited lipid peroxidation and restored the levels of endogenous antioxidants to normal.

To conclude, Spirulina had a signiﬁcant effect on scavenging free radicals, thereby protecting the organs from damage caused by the exposure to lead. Further more, Spirulina showed a signiﬁcant (p < 0.05) decrease in the deposition of lead in the brain. Copyright © 2003 John Wiley & Sons, Ltd.
The Gts1 protein stabilizes the autonomous oscillator in yeast
Authors: Adams Claire A. , Kuriyama Hiroshi , Lloyd David , Murray Douglas B.
Published: April 2003

Continuous cultures of Saccharomyces cerevisiae show a robust autonomous temperature compensated oscillation in many metabolic functions. Respiratory activity, a convenient output to measure, oscillates with a period of 40 min. Deletion of GTS1, whose protein product has homology to the circadian per protein, has been implicated in temporal events within yeast, causes a reduction in periodicity to 18 min (wild‐type period 40–60 min). The dilution rate was steadily increased from 0.04/h to 0.085/h and the oscillation stabilized after four to six dilutions. However, Gts1p's involvement in the maintenance and generation of metabolic synchrony, and in the central oscillating loop, appear to be minimal, as the mutant oscillation was robust and autonomous. Deletion of GTS1 did cause decreased temperature compensation of the period of the oscillation from Q10 = 1.07 for the wild‐type to Q10 = 1.6 for the mutant. Also the degree of nutrient compensation observed for the wild‐type was not observed in the GTS1‐null mutant strain. It is postulated that Gts1p is involved in the mechanism that communicates external conditions, such as temperature, to the central oscillating loop. Copyright © 2003 John Wiley & Sons, Ltd.
Increased rates of tRNA charging through modification of the enzyme‐aminoacyl‐adenylate complex of phenylalanyl‐tRNA synthetase
Authors: Ibba Michael , Johnson Christopher M. , Hennecke Hauke , Fersht Alan R.
Published: April 2003

The transfer of amino acid to tRNA by Escherichia coli phenylalanyl‐tRNA synthetase (PheRS) was studied using replacements of Ala294 in the α subunit previously shown to have modified amino acid specificity. Steady‐state analysis of tRNA charging showed little difference between wild‐type and mutants, whereas pre‐steady‐state analysis revealed higher rates of tRNA charging by both the A294S PheRS‐phenylalanyl adenylate and the A294G PheRS‐p‐Cl‐phenylalanyl adenylate. The decrease in energy required for the formation of the transition state of amino acid transfer in these mutants could be related to a weaker binding of the amino acid in the aminoacyl adenylate complex. Thus a compromise appears to exist between amino acid activation and tRNA charging, because slowing down the first step increases the rate of the second step, possibly as a result of decreased stability of the PheRS·amino acid‐AMP complex.
Nucleotide bindind by the synapse associated protein SAP90
Authors: Kistner Ute , Garner Craig C. , Linial Michal
Published: April 2003

The rat synapse associated protein SAP90 is a member of a superfamily of potential guanylate kinases localized at cell‐cell contact sites. This superfamily includes the synapse associated protein SAP97, a close relative of SAP90, the Drosophila tumor suppressor gene product dlg‐Ap, the mammalian zonula occludens proteins ZO‐1 and ZO‐2 and the erythrocyte protein p55. Here we show that SAP90 specifically binds GMP in the micromolar range while binding to ATP, GDP and ADP is at a much lower affinity (10–25 mM), whether or not binding is detected for other guanine and adenine nucleotides. No guanylate kinase activity of SAP90 was detected under our experimental conditions. The importance of the GMP binding capacity per se and an evolutionary role for conserving of the guanylate kinase domain in this superfamily are discussed.
UCN‐01, an anti‐tumor drug, is a selective inhibitor of the conventional PKC subfamily
Authors: Mizuno Keiko , Noda Kumi , Ueda Yoshihiko , Hanaki Hisao , Saido Takaomi C. , Ikuta Tohgo , Kuroki Toshio , Tamaoki Tatsuya , Hirai Syu-ichi , Osada Shin-ichi , Ohno Shigeo
Published: April 2003

A selective PKC inhibitor, UCN‐01, was shown to exhibit anti‐tumor activity in vitro and in vivo. We investigated UCN‐01 with respect to isozyme‐specific PKC inhibition using purified recombinant or rabbit brain PKC isozymes, cPKCα, β and γ, nPKCδ, ϵ and ν, and aPKCζ. Of the PKC isozymes examined, cPKCα was inhibited by UCN‐01 most effectively (K
i = 0.44 nM), suggesting cPKCα is the prime candidate for the physiological target of UCN‐01. The K
i values of UCN‐01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the K
i values for nPKC isozymes are about 20 nM. Moreover, the K
i value for aPKCζ is 3.8 μM. Thus, UCN‐01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKCζ were examined and compared with those for cPKCα.
Molecular diagnosis of transthyretin Met30 mutation in an Italian family with familial amyloidotic polyneuropathy
Authors: Strocchi Paola , Tang Xue-Ming , Cambi Franca
Published: April 2003

We report the molecular analysis of the transthyretin gene in a large Italian pedigree with familial amyloidotic polyneuropathy and demonstrate the presence of a Met30 mutation. The usefulness of the genetic analysis in the identification of presymptomatic persons and the diagnosis of individuals with partial symptoms is discussed.
Involvement of Mg2+ in terminating Ca2+ release in cultured rat skeletal muscle
Authors: Suda Norio
Published: April 2003

Combined patch‐clamp and fura‐2 measurements were performed to investigate the mechanism that terminates Ca2+ release in rat skeletal myoballs. When cells were intracellularly perfused with solution containing 1 mM free Mg2+, the caffeine (10 mM)‐induced Ca2+ transient was abruptly terminated by membrane repolarization (−70 mV). With low intracellular Mg2+ (e.g. 50 μM) perfusion, however, repolarization failed to terminate the caffeine transient. The results show that intracellular Mg2+ is necessary for repolarization‐induced closing of the Ca2+ release channel.
Regulation of α1‐antichymortrypsin synthesis in cells of epithelial origin
Authors: Cichy Joanna , Potempa Jan , Chawla Rajender K. , Travis James
Published: April 2003

Oncostatin M, interleukin‐1 and the glucocorticoid analog, dexamethasone, have been identified as potent stimulators of α1‐antichymotrypsin production in various cells of epithelial origin. Although being able to act individually, these factors exerted a dramatic increase in α1‐antichymotrypsin synthesis when administrated in combination. Their stimulatory effect was independent of the levels of constitutive synthesis of this inhibitor, which was already high in lung‐ and breast‐ and low in skin‐derived epithelial cells. Since α1‐antichymotrypsin controls chymotrypsin‐like proteinases which are released during inflammation, these data support the concept that local synthesis of this inhibitor may be important in reducing tissue damage associated with this process.
A rapid, simple method for the isolation and characterization of the photoreceptor of Dictyostelium discoideum amoebae
Authors: Schlenkrich Thomas , Porst Markus , Häder Donat-P.
Published: April 2003

A membrane‐bound 45.5 kDa protein has been isolated from Dictyostelium discoideum amoebae. It shows an absorption spectrum, which closely resembles the action spectrum for amoebal phototaxis, leading to the conclusion that this protein might play an important role in the photoreception of Dictyostelium amoebae. For further characterization we employed phase partition in an aqueous polymer two‐phase system, which was developed by Widell and Larsson for the separation of plasma membrane proteins of higher plants. This method clearly shows that the 45.5 kDa protein is a plasma membrane protein and not an intracellular protein. Furthermore, by using phase systems with increasing polymer concentrations, this simple and rapid purification of plasma membrane proteins allowed us to isolate the putative photoreceptor in one single step. Compared to standard biochemical methods phase partition provides an enormous facilitation of the isolation of D. discoideum membrane proteins.
Cloning of cDNA for human granzyme 3
Authors: Przetak Melinda M. , Yoast Sienna , Schmidt Brian F.
Published: April 2003

A serine protease gene was cloned from cDNA prepared from tissue isolated from human ascites. The gene codes for a protein of 264 amino acids, identified as human granzyme 3 by the N‐terminal amino acid sequence. Granzyme 3 has the expected features of the chymotrypsin family of serine proteases, and is closely related to other human granzymes (40–45% identity). However, the closest granzyme 3 homologue is the recently characterized rat tryptase, RNK‐Tryp‐2 (75% identity). From Northern blots, granzyme 3 appears to be highly expressed in peripheral blood leukocytes, spleen, thymus, and lung tissues.
Relaxing the substrate specificity of an aminoacyl‐tRNA synthetase allows in vitro and in vivo synthesis of proteins containing unnatural amino acids
Authors: Ibba Michael , Hennecke Hauke
Published: April 2003

It has previously been demonstrated that the unnatural amino acid p‐Cl‐phenylalanine can be attached to tRNAPhe by a modified phenylalanyl‐tRNA synthetase with relaxed amino acid substrate specificity. We show that this modification to the translational machinery of Escherichia coli is the only requirement for the incorporation of either p‐Cl‐ or p‐Br‐phenylalanine into full‐length luciferase in vitro. The incorporation of p‐Cl‐phenylalanine was also demonstrated in vivo using a suitably modified host strain. These results represent the first description of the incorporation into a protein in vivo of an unnatural amino acid which is normally rejected by the cellular translational machinery.
Influence of extracellular matrices on ganglioside pattern of two hepatoma cell lines with different adhesive properties
Authors: Fritsch Martin , Geilen Christoph C. , Heidrich Claudia , Reutter Werner
Published: April 2003

A cell culture model was developed to investigate the involvement of gangliosides in cell‐matrix adhesion. Two cell lines with different adhesive properties derived from solid Morris hepatoma 7777 were established. Cultured in horse serum‐containing medium, the adhesive cell line (MH 7777A) adheres and spreads on uncoated culture dishes, whereas the revertant cell line (MH 7777A>N) does not adhere and grows in suspension. The adhesiveness of both cell lines is dependent on the coating protein used (none, bovine serum albumin, fibronectin or collagen I) and the horse serum concentration in the culture medium. Both cell lines, although of the same origin, differed in their ganglioside composition. The most abundant ganglioside of both MH 777A and MH 7777A>N cell lines was fucosyl‐GM1, 0.78 and 0.72 μg per mg cellular protein, respectively. The GM3 and GD1a content of MH 7777A>N cells was significantly higher than that of MH 7777A cells. Furthermore, a matrix‐dependency of the ganglioside pattern of both cell lines was demonstrated.
The phorbol 12‐myristate 13‐ acetate (PMA)‐induced oxidative burst in rat peritoneal neutrophils is increased by a 0.1 mT (60 Hz) magnetic field
Authors: Roy Sashwati , Noda Yasuko , Eckert Valorie , Traber Maret G. , Mori Akitane , Liburdy Robert , Packer Lester
Published: April 2003

Magnetic fields (MF) may affect biological systems by increasing free radical concentrations. To test this, we have investigated whether low frequency (60 Hz) low intensity (0.1 mT) MF can modulate the phorbol 12‐myristate 13‐ acetate (PMA) induced respiratory burst in primed rat peritoneal neutrophils, followed in real time using the dye 2′,7′‐dichlorofluorescin (DCFH), which reacts with free radical‐derived oxidants such as H2O2 (which is formed from the dismutation of superoxide) to become 2′,7′‐dichlorofluorecein (DCF), a highly fluorescent compound. In the presence of the MF, a 12.4% increase in the fluorescence signal was observed in PMA‐stimulated neutrophils (n = 5, P < 0.02, 18 pairs of measurements). We believe this represents the first experimental observation of MF influencing events involving free radical species generated during signal transduction in living cells.