bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomale röntgenstreuung zur erforschung makromolekularer strukturen
Authors: Stuhrmann Heinrich B.
Published: April 2003

The possibilities of anomalous X‐ray scattering for the investigation of semi‐ or noncrystalline macromolecular structures are discussed on the grounds of the first successful measurements of anomalous scattering of iron in dissolved hemoglobin. As anomalous scattering of this kind of material is limited to the near vicinity of the X‐ray absorption edges, the use of synchrotron radiation appears to be obligatory. The anomalous dispersion of the atomic form factors slightly increases with the atomic number. Anomalous dispersion is nearly doubled when going from the K‐absorption edge to the LIII‐absorption edge and from there to the Mv‐ absorption edge. Therefore, the use of anomalous dispersion in the soft X‐ray region is quite promissing. With the planned extension of the spectral range accessible to X‐ray diffractometers from 3 Å to 6 Å, one would get hold of the anomalous scattering of very important elements in macromolecular structures, like phosphorus, sulfur, and chlorine.
Structural studies on the Escherichia coli type‐27 capsular polysaccharide
Authors: Chakraborty Ajit K.
Published: April 2003

The primary structure of the Escherichia coli serotype K‐27 capsular polysaccharide has been investigated. The capsular polysaccharide was isolated from Escherichia coli strain E56b, serotype 08:K27(A):H‐. Using methylation analysis, characterization of oligosaccharides obtained by partial acid hydrolysis and enzymic degradation, as well as 1H nuclear magnetic resonance, the primary structure of the K‐27 glycan has been elucidated. The polymer was found to consist of tetrasaccharide repeating units of the following structure:
Inhibition of thermal and thermooxidative degradation of polystyrene by polyconjugated polymers with anthracene repeating units
Authors: Schopov Ivan , Jossifov Christo
Published: April 2003

It was found that three polyconjugated polymers with anthrancene repeating units slow down the thermal and thermooxidative degradation of polystyrene. This effect is explained by charge transfer complex formation between the radicals formed during the degradation of polystyrene and the polyconjugated polymers as donors.
Immobilisation du complexe de nickel de l'histidine L(+) sur des supports macromoléculaires hydrophiles
Authors: Spassky Nicolas , Reix Michel , Sepulchre Marie‐Odile , Guetté Jean‐Paul
Published: April 2003

N‐(4‐vinylbenzyl)‐L‐histidine (5) and the corresponding methyl ester were synthesized by reacting L‐histidine or L‐histidine methyl ester with 4‐formylstyrene. N‐(4‐vinylbenzyl)‐L‐histidine methyl ester was radically copolymerized with various amounts of 2‐hydroxyethyl methacrylate and ethylene dimethacrylate, leading to resins of different degrees of hydrophilicity and crosslinking. After saponification of the histidine ester groups, the resins were chelated with Ni2+ salt in order to be used as polymeric catalysts in enantioselective ester hydrolysis reactions.
Etude de la structure ramifiée du polyéthylène basse densité par viscosité et diffusion de la lumière de fractions issues de la chromatographie d'exclusion gpc
Authors: Hert Marius , Strazielle Claude
Published: April 2003

Fractions of high density polyethylene (PEhd) and low density polyethylene (PEld) obtained from gel permeation chromatography were studied by viscometry and light scattering. The variations of the intrinsic viscosity [η], the molecular weight M̄w, and the radius of gyration Rg for PEhd and PEld were compared with one another and the relationships [η] vs M and Rg vs. M for PEhd were established. The dependence of structural parameters g = (Rg2)branch/(Rg2)linear and g′ = [η]branch/[η]linear on the molecular weight was determined for three samples of PEld.
Liquid crystalline main chain polymers with highly flexible siloxane spacers
Authors: Aguilera Carlos , Bartulin Juan , Hisgen Bernd , Ringsdorf Helmut
Published: April 2003

The synthesis and the phase behaviour of liquid crystalline main chain polymers are described. In these poly‐ and copolyesters the mesogenic units are linked by highly flexible oligodimethylsiloxane spacers. The comparison of their phase behaviour with that of polyesters known from the literature shows that dimethylsiloxane spacers as a replacement for alkyl spacers are leading to a drastic decrease of the transition temperatures. Depending on the length of the spacer glass transitions as low as −111°C can be achieved. The widths of the liquid crystalline phases thereby are retained up to a spacerlength of 13 oxydimethylsilanediyl (dimethylsiloxane) units. The homopolyesters mainly show smectic phases. In contrast to this nematic phases are found for copolyesters in which either the spacerlength or the mesogenic unit was varied. In one case a nematic phase was found over a temperature range of 311°C.
On the molecular weight determination by vapour pressure osmometry, 4. Experimental proof of the deviation of MVPO from Mn
Authors: Marx‐Figini Marianne , Tagliabue Marcelo , Figini Rubén V.
Published: April 2003

The kind of molecular weight average MVPO resulting from vapour pressure osmometry (VPO) measurements on solutions of paucimolecular polymer mixtures of different compositions is studied with a Hewlett Packard Model 302 B. Recent theoretical calculations which predicted that MVPO > Mn are confirmed. The experimentally found quotient MVPOMn is between 1,04 and 1,26, being the greater, the greater is the polydispersity of the mixture, which is agreement with the former mathematical derivations.
Polymer conformation and NMR chemical shifts, 7. Conformational analysis of random copolymers
Authors: Sato Kota , Koinuma Hideomi , Hirai Hidefumi
Published: April 2003

A method is developed for the conformational analysis of copolymers with randomly distributed stereo‐ and comonomer‐sequences. The conformational probabilities of dyad sequences constituting a random copolymer chain are calculated as a function of the copolymer composition which is derived from the monomer reactivity ratios and the comonomer feed ratio. The applicability of this method is verified in the conformational analyses of poly(methyl acrylate‐co‐styrene) and poly(methyl methacrylate‐co‐styrene). The calculation indicates that the conformational stabilities of dyad sequences are scarcely dependent on the copolymer composition in the former copolymer, whereas they are susceptible to the composition in the latter copolymer. This conformational behavior apparently reflects the geometrical difference between the copolymers: the former is composed of two mono‐substituted monomers and the latter of sterically nonequivalent monomers, viz. mono‐ and di‐substituted vinyl compounds. The composition‐dependences of 13C NMR chemical shifts of these copolymers are interpreted, based on the conformational calculation by this method.
Application of spin trapping technique to radical polymerization, 20. Vinyl polymerization initiated by triphenylboron
Authors: Sato Tsuneyuki , Fukumura Naoki , Otsu Takayuki
Published: April 2003

Triphenylboron was found to serve as an effective radical initiator for vinyl monomers without any participation of oxygen. The polymerization of methyl methacrylate (MMA) initiated by triphenylboron was studied kinetically in acetonitrile. The over‐all activation energy of the polymerization was calculated to be 60,3 kJ/mol. The polymerization rate (Rp) can be expressed as follows: Rp = k (Triphenylboron)0,9[MMA]1,8. Spin trapping studies revealed formation of phenyl radicals by decomposition of triphenylboron in the absence of oxygen. Decomposition of triphenylboron in toluene yielded o‐, m‐, and p‐methylbiphenyls, the isomer ratio of which was close to that observed in the decomposition of benzoyl peroxide in toluene. Furthermore, an ethanol solution of triphenylboron was found to give a very stable boron centered radical. From these findings, the initiation mechanism for the polymerization is proposed and discussed.
Functional monomers and polymers, 103. Synthetic application of polystyrene‐bound chloropyrimidine and chloropurine as dehydrating and desulfhydrating reagents
Authors: Kondo Koichi , Murakami Mikio , Takemoto Kiichi
Published: April 2003

Poly{1‐[4‐(4‐chloro‐2‐oxo‐1,2‐dihydropyrimidin‐1‐ylmethyl)phenyl]‐ethylene} (1b) was pre‐pared by condensation of chloromethylated polystyrene and uracil and subsequent reaction with POCl3, and used as dehydrating and desulfhydrating reagent for the preparation of hydro‐xamates, acid chlorides, nitriles, and lactones. Other types of polymeric reagents, poly{1‐[4‐(2,6‐dichloro‐4‐pyrimidinylaminomethyl)phenyl]ethylene} (4) and poly{1‐[4‐(6‐chloro‐9(7)‐puri‐nylmethyl)phenyl]ethylene} (5) were prepared analogously. It was found that 1 b shows the highest activity in these syntheses as compared with the other polymeric reagents 4 and 5.
Asymmetric selective oligomerization of chloromethyloxirane
Authors: Tezuka Yasuyuki , Ishimori Michihiro , Tsuruta Teiji
Published: April 2003

Chloromethyloxirane (CMO) undergoes an asymmetric selective oligomerization with a binary catalyst system comprised of triethylaluminium and an optically active cobalt complex, N,N'‐disalicylidene‐(1 R)‐1,2‐cyclohexanediyldiaminatocobalt(II). A series of optically active oligomers obtained were isolated and characterized. Two kinds of linear oligomers were produced with respect to the end groups, namely epoxy‐ and halohydrin‐ended oligomers. A mechanism for the selective formation of linear oligomers by the present catalyst system is proposed.
Copolymerization of vinyl chloride and methyl acrylate catalyzed by ethylaluminium compounds
Authors: Florjańczyk Zbigniew , Kuran Witold , Sitkowska Jadwiga
Published: April 2003

The copolymerization of vinyl chloride (VC) and methyl acrylate (MA) in the presence of ethylaluminium compounds (C2H5AlCl2, (C2H5)2AlCl, and (C2H5)3Al) at low ethylaluminium compound (EAC)/MA mole ratios was investigated. An alternating copolymer was produced in this reaction when an excess of VC in the initial monomer feed was used. The addition of dibenzoyl peroxide (BPO) to the systems containing EAC resulted in an increase of the alternating copolymer yield. In polymerization systems containing EAC resulted in an increase of the alternating copolymer yield. In polymerization systems containing EAC combined with VOCl3 an enhancement of the alternating copolymer yield and formation of VC‐rich copolymers were observed. In the polymerization system with (C2H5)3AlVOCl3 a VC‐rich copolymer was the main product. It was concluded that VC‐rich copolymers are formed in the random radical copolymerization which occurs when most of EAC is complexed by the alternating copolymer chain. The structure of alternating and VC‐rich copolymers was studied in detail by means of 13C NMR spectroscopy.
Anionic and radical polymerization of p‐triphenyl‐ and p‐tributylgermyl‐styrenes
Authors: Hirao Akira , Shiraishi Yoshinobu , Martinez Francisco , Phung Hoang Minh , Nakahama Seiichi , Yamazaki Noboru
Published: April 2003

Anionic polymerization of p‐triphenylgermylstyrene (1a) and p‐tributylgermylstyrene (1b) were investigated under high vacuum conditions (≈10−6 mbar). Both 1a and 1b were readily polymerized with sodium naphthalide, potassium naphthalide, or α‐methylstyrylsodium oligomers to form “living polymers”. The addition of α‐methylstyrene to these living systems gave the triblock copolymer, poly(α‐methylstyrene‐b‐p‐triphenylgermylstyrene‐b‐α‐methylstyrene). Both monomers were also polymerized radically with AIBN as initiator. Some physical properties of the resulting polymers were examined.
Electron transfer process in the microdomains of poly(sodium styrenesulfonate)‐poly(alkylene viologen) complexes
Authors: Ohno Hiroyuki , Hosoda Naohiro , Tsuchida Eishun
Published: April 2003

The electron transfer process in the microdomain of a polyion complex composed of poly(sodium styrenesulfonate), (syst. name: poly[sodium 1‐(4‐sulfonatophenyl)ethylene]), and poly(alkylene viologen)s 1 with 3 to 10 methylene groups between two adjacent viologen units was analyzed by means of voltammetry with a rotating disc electrode. Although the stability of 1 on the graphite electrode was improved by the formation of a polyion complex with poly(sodium styrenesulfonate), a smaller surface charge was observed in the polyion complex as compared with the electrode coated with poly(alkylene viologen) alone. Since the migration of the counter ion was clarified to be indispensable for the electron transfer in this case, the microdomain of polyion complexes should be formed by tightly‐shrunk polyelectrolyte chains. Furthermore, the electron transfer in the microdomain of the polyion complex is hardly detected, when the electrode is coated with an excess of the complex. The electron transfer strongly depended on the average distance between two adjacent redox sites in the matrix. These matrixes were suggested to be controlled by the subtle balance of hydrophobicity and charge density of 1.
Anwendung des komplexmodells zur beschreibung der bruttopolymerisationsgeschwindigkeit bei copolymerisationen mit ausgeprägter beteiligung von EDA‐komplexen
Authors: Braun Dietrich , Czerwinski Wojciech
Published: April 2003

Equations are derived for free radical‐initiated copolymerization of monomers with significant charge‐transfer interactions, which describe the overall rate of polymerization. Both the simplified and the complete steady‐state principle has been applied. The equations obtained were examined with literature data for the monomer systems styrene/maleic anhydride and styrene/acrylonitrile. It is seen from the calculations that a nearly quantitative interpretation of experimental results including a wide range of monomer concentrations is feasible by means of the complete rate equation. In contrast, the simplified model does not even permit a qualitative interpretation of the experimental results.
Polymerization of acrylonitrile initiated by the redox system manganese (III) acetate/ethylene glycol
Authors: Samal Narayan C. , Mishra Ranu , Senapati Manjushree , Nayak Nrusingh C. , Patnaik Lalit N. , Rout Mahendra K.
Published: April 2003

The kinetics of polymerization of acrylonitrile initiated by the redox system manganese (III) acetate/ethylene glycol was studied in aqueous sulfuric acid medium in the temperature range from 30 to 40°C. The effect of varying the concentrations of monomer (M), acetic acid, and sulfuric acid and the addition of some electrolytes on the rate of polymerization (Rp) was investigated. Based on the experimental observations of the dependence of (Rp) on various parameters, a suitable kinetic scheme could be proposed. The plot of Rp2[M]2 vs. [M] was found to be linear, a striking general phenomenon observed for all the substrates we have studied in this laboratory.
UV‐photometrische analyse kationisch erzeugter polystyrole, 1. Nachweis des covalenten einbaus von acylresten aus aromatischen acylperchloraten
Authors: Kämmerer Hermann , Seyed‐Mozaffari Ahmad
Published: April 2003

Polymerization of styrene was found not to take place with 4‐phenylazobenzoyl perchlorate in benzene solution. 4‐Biphenylcarbonyl perchlorate, however, initiates styrene polymerization under the same conditions leading to a product not containing acyl groups as indicated by UV spectroscopic analysis. 4‐Phenylazobenzoyl, 2‐naphthoyl, and 9,10‐dioxo‐2‐anthracenecarbonyl perchlorate (6b, 7b, and 8b), prepared form silver perchlorate and the corresponding acyl chlorides 6a, 7a, and 8a in styrene, were found to initiate the polymerization of styrene under anhydrous conditions at −25°C in the dark. By UV spectroscopy it could be shown that the resulting polymers contain covalently bound acyl groups. Their absorption bands correspond to those of model compounds 6c, 7c, 8c, and 7d, respectively. IR spectra of mixtures of polystyrene with model compounds show that incorporation of acyl groups can be detected by their carbonyl absorption in the region of 1680 – 1700 Cm−1 only in polystyrenes having molar masses <50 000.
Enthalpy of dilution of polystyrene/diethyl ketone
Authors: Fujihara Ichiro , Sakuta Takashi , Kagemoto Akihiro
Published: April 2003

The enthalpy of dilution at 298,15 K was measured for the system polystyrene/diethyl ketone with a recently constructed flow type microcalorimeter, and the heat interaction parameter, χh, was estimated. It was found that χh, for this system is very small and negative and that its absolute value decreases with increasing molecular weight of the polymer. By comparison with other ketone systems measured previously, it was found that a polar solvent makes the polystyrene molecule energetically stable in solution.
Acidolytic polymerization of N‐methyldodecanelactam
Authors: Puffr Rudolf , Tuzar Zdeněk , Mrkvičková Libuše , Šebenda Jan
Published: April 2003

The polymerization rate of 1‐methylazacyclotridecan‐2‐one (N‐methyldodecanelactam) (1) initiated with dodecanoic acid (2) can be described within the whole range of conversions in terms of the simple relation In ([1]0/[1]) = k[2]0t, in spite of the complexity of the overall reaction scheme. The rate constants (k) determined for 240, 260, and 280°C are 0,32, 1,21, and 3,4 kg · mol−1 h−1, respectively, and the constants of the Arrhenius equation are A = 6,6 · 1013kg · mol−1 h−1, E = 140 kJ · mol−1. The resulting poly(N‐methyldodecaneamide) (3) is a semicrystalline polymer (m.p. 65°C), soluble in polar organic solvents. The following constants of the Mark‐Houwink equation were determined for solutions of this polyamide: for 5000 < M̄w < 150 000 g · mol−1 at 25°C in THF (2‐propanol), K = 0,124 (0,161) cm3 · g−1, a = 0,59 (0,56); for 5 000 < M̄w < 80 000 g · mol−1 at ⊖‐temperature = 30,5°C in 1,4‐dioxane, K = 0,215 cm3 · g−1, a = 0,50. Analyses of molar masses, both theoretical and experimental (light‐scattering, GPC, osmometry, end groups), indicate that at the polymerization temperature of 280°C side reactions already take place, reflected in random cleavage and in branching of chains.
Synthesis and characterization of some aliphatic polyamides containing 4,4′‐azodiphenylene units
Authors: Chidambaram S. , Nanjan M. J.
Published: April 2003

Polyamides containing azo groups were prepared by the phosphorylation method from 4,4′‐diaminoazobenzene and malonic, succinic, glutaric, adipic, azelaic, sebacic, or chlorosuccinic acid. The polymers were characterized by their viscosity and solubility, and by UV‐visible and IR spectroscopy, TG, and DTA.
Thermomechanical study of oriented poly(ethylene terephthalate): Effect of homogeneous deformation and moisture absorption
Authors: Rietsch François
Published: April 2003

The homogeneous drawing behaviour of poly(ethylene terephthalate) (PET) at T=80°C has been studied by glass transition temperature analysis. At the first stage of homogeneous drawing (draw ratios λp up to 3,0), the results as compared to the statistical Gibbs‐DiMarzio theory, suggest that the rate of the segmental motion increases with the draw ratio. In a second zone of moderate and high draw ratios (λp > 3) a non‐negligible loss‐entropy component occurs as predicted by the Gibbs‐DiMarzio theory of isovolume strained network chains. The moisture absorption at room temperature causes a decrease in glass transition temperature which is more pronounced at higher draw ratios.
Global stabilization and asymptotic tracking for a class of nonlinear systems by means of time‐varying feedback
Authors: Karafyllis I. , Tsinias J.
Published: April 2003

A simple backstepping design scheme is proposed and sufficient conditions for non‐uniform in time global stabilization for parameterized systems by means of time‐varying feedback are established. Our methodology is applicable to a special class of systems that in general cannot be stabilized by static feedback and includes non‐holonomic systems in chained form. For this class of systems the main results on feedback stabilization enable us to derive sufficient conditions for the solvability of the tracking problem. Copyright © 2003 John Wiley & Sons, Ltd.
Size (and competition) among organizations: modeling scale‐based selection among automobile producers in four major countries, 1885–1981
Authors: Dobrev Stanislav D. , Carroll Glenn R.
Published: April 2003

Based on previous empirical research, size is perhaps the most powerful explanatory organizational covariate in strategic analysis. We suggest that theoretical arguments about size be examined carefully to specify models with explicit comparison sets and with mechanisms linking size and underlying processes to outcomes. We illustrate the approach here by advancing arguments about scale competition within an organizational population. In this effort, we feature a theoretical model of scale‐based selection, which posits that a firm's chances of survival decrease with its aggregate distance from larger competitors on a transformed size gradient. The model assumes that the appropriate comparison set consists of all contemporaneous similar organizations competing on the basis of scale and operating in a localized geographic setting. We argue that aggregate distance of a focal firm from larger other firms (a specific form of relative position in the size distribution) reflects the extent to which it can capitalize on potential competitive advantages of scale emanating from economic, political, and social processes. Analyzing the mortality rates of large organizations across the entire histories of automobile industries in four major countries provides support for the theory. We discuss the general implications of our findings for strategic and organizational analysis. Copyright © 2003 John Wiley & Sons, Ltd.
Altered fetal circulation in type‐1 diabetic pregnancies
Authors: Lisowski L. A. , Verheijen P. M. , de Smedt M. M. C. , Visser G. H. A. , Meijboom E. J.
Published: April 2003

Objective

Type‐I diabetic pregnancies are associated with congenital cardiac malformations, fetal cardiomyopathy, venous thrombosis and altered placental vascularization, even with tight maternal glucose control. The aim of this study was to investigate if, with good glucose control achieved with continuous subcutaneous insulin infusion, normal blood flow within the fetal heart can be achieved.

Methods

Seventeen fetuses of women with well‐controlled type‐I diabetes were studied longitudinally to evaluate effects on the fetal circulation. Doppler frequency shift tracings, valve diameters and intercept angles were measured at right and left atrioventricular valve orifices at 4‐week intervals starting at 15 weeks' gestation. Atrioventricular valve flow was calculated and compared to normal fetal data obtained in previous studies.

Results

Maximum and mean temporal velocities across the atrioventricular valves increased in both groups during gestation but significantly more in fetuses of type‐I diabetic pregnancies. Combined ventricular output, both absolute and per kg estimated fetal weight, were also greater in these fetuses. In the normal group the ratio of the left/right ventricular output decreased significantly during gestation (from 1.34 ± 0.28 to 1.08 ± 0.28 standard deviations), but in type‐I diabetic pregnancies this decrease did not occur (1.2 ± 0.26 to 1.25 ± 0.29 standard deviations).

Conclusions

These data indicate that there are significant differences in the fetal circulation between normal pregnancy and well‐controlled type‐I diabetic pregnancy, suggesting the existence of a compensatory mechanism which increases fetal cardiac output and causes cardiac hypertrophy. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Gemeinschafts- und personzentrierte Lebensziele von männlichen Jugendlichen in Sambia:
Authors: Hofer Jan
Published: April 2003

Zusammenfassung. Dieser Artikel betrachtet Zusammenhänge zwischen kulturellem Kontext und der Generierung von Lebenszielen. Anhand des Fragebogens GOALS wurden Daten zu Lebenszielen von 250 männlichen Jugendlichen in Sambia gesammelt. Sowohl die Anzahl der Zielkategorien als auch deren inhaltliche Zusammensetzung weichen von der in einer deutschen Schülerstichprobe gefundenen Strukturierung der Items ab. Faktorenanalytisch ließen sich zwei übergeordnete Zielkategorien identifizieren: gemeinschafts- und personzentrierte Lebensziele. Gemeinschaftszentrierte Lebensziele werden von den Jugendlichen signifikant wichtiger eingeschätzt als personzentrierte Lebensziele. Unterschiede zeigen sich auch in der Bewertung der Erreichbarkeit und des Erfolgs bei der Realisierung beider übergeordneter Zielkategorien. Diese Befunde werden auf der Basis kulturspezifischer Sozialisationsbedingungen interpretiert. In den expliziten Motiven der sambischen Jugendlichen (Lebensziele) lassen sich deutlich traditionelle kulturelle Orientierungen nachweisen, die auf eine starke Anbindung des Individuums an signifikante Bezugspersonen oder -gruppen abzielen. Der Kontakt mit kulturfremden Elementen, beispielsweise operationalisiert über das Ausmaß an formaler, an westlichen Standards ausgerichteter Schulbildung, scheint die Generierung von Lebenszielen durch die Adoleszenten dagegen weit weniger zu beeinflussen.
Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta
Authors: Sandell Lisa L. , Guan Xiao-Juan , Ingram Robert , Tilghman Shirley M.
Published: April 2003

To increase our understanding of imprinting and epigenetic gene regulation, we undertook a search for new imprinted genes. We identifiedGatm, a gene that encodesl-arginine:glycine amidinotransferase, which catalyzes the rate-limiting step in the synthesis of creatine. In mouse,Gatmis expressed during development and is imprinted in the placenta and yolk sac, but not in embryonic tissues. TheGatmgene maps to mouse chromosome 2 in a region not previously shown to contain imprinted genes. To determine whetherGatmis located in a cluster of imprinted genes, we investigated the expression pattern of genes located nearGatm: Duox1-2, Slc28a2, Slc30a4and a transcript corresponding to LOC214616. We found no evidence that any of these genes is imprinted in placenta. We show that a CpG island associated withGatmis unmethylated, as is a large CpG island associated with a neighboring gene. This genomic screen for novel imprinted genes has elucidated a new connection between imprinting and creatine metabolism during embryonic development in mammals.
Majority of divergence between closely related DNA samples is due to indels
Authors: Britten Roy J. , Rowen Lee , Williams John , Cameron R. Andrew
Published: April 2003

It was recently shown that indels are responsible for more than twice as many unmatched nucleotides as are base substitutions between samples of chimpanzee and human DNA. A larger sample has now been examined and the result is similar. The number of indels is ≈1/12th of the number of base substitutions and the average length of the indels is 36 nt, including indels up to 10 kb. The ratio (
R
u
) of unpaired nucleotides attributable to indels to those attributable to substitutions is 3.0 for this 2 million-nt chimp DNA sample compared with human. There is similar evidence of a large value of
R
u
for sea urchins from the polymorphism of a sample of
Strongylocentrotus purpuratus
DNA (
R
u
= 3–4). Other work indicates that similarly, per nucleotide affected, large differences are seen for indels in the DNA polymorphism of the plant
Arabidopsis thaliana
(
R
u
= 51). For the insect
Drosophila melanogaster
a high value of
R
u
(4.5) has been determined. For the nematode
Caenorhabditis elegans
the polymorphism data are incomplete but high values of
R
u
are likely. Comparison of two strains of
Escherichia coli
O157:H7 shows a preponderance of indels. Because these six examples are from very distant systematic groups the implication is that in general, for alignments of closely related DNA, indels are responsible for many more unmatched nucleotides than are base substitutions. Human genetic evidence suggests that indels are a major source of gene defects, indicating that indels are a significant source of evolutionary change.
Low T cell receptor expression and thermal fluctuations contribute to formation of dynamic multifocal synapses in thymocytes
Authors: Lee Sung-Joo E. , Hori Yuko , Chakraborty Arup K.
Published: April 2003

Mature T cell activation and selection of immature T cells (thymocytes) are both initiated by binding of T cell receptor (TCR) molecules on the surface of T cells to MHC peptide (MHCp) molecules on the surface of antigen-presenting cells. Recent experiments have shown that the spatial pattern of receptors and ligands in the intercellular junction (synapse) is different during thymocyte selection compared with mature T cell activation. Using a statistical mechanical model, we show that lower TCR expression in thymocytes contributes to effecting these differences. An analogy with the phase behavior of simple fluids helps clarify how, for low TCR expression, thermal fluctuations lead to the dynamic synapse patterns observed for thymocytes. We suggest that a different synapse pattern resulting from lower TCR expression, which could mediate differential signaling, may be the reason why TCR expression level is low in thymocytes.
Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch
Authors: Agate Robert J. , Grisham William , Wade Juli , Mann Suzanne , Wingfield John , Schanen Carolyn , Palotie Aarno , Arnold Arthur P.
Published: April 2003

In mammals and birds, sex differences in brain function and disease are thought to derive exclusively from sex differences in gonadal hormone secretions. For example, testosterone in male mammals acts during fetal and neonatal life to cause masculine neural development. However, male and female brain cells also differ in genetic sex; thus, sex chromosome genes acting within cells could contribute to sex differences in cell function. We analyzed the sexual phenotype of the brain of a rare gynandromorphic finch in which the right half of the brain was genetically male and the left half genetically female. The neural song circuit on the right had a more masculine phenotype than that on the left. Because both halves of the brain were exposed to a common gonadal hormone environment, the lateral differences indicate that the genetic sex of brain cells contributes to the process of sexual differentiation. Because both sides of the song circuit were more masculine than that of females, diffusible factors such as hormones of gonadal or neural origin also likely played a role in sexual differentiation.
Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation
Authors: Caplice Noel M. , Bunch T. Jared , Stalboerger Paul G. , Wang Shaohua , Simper David , Miller Dylan V. , Russell Stephen J. , Litzow Mark R. , Edwards William D.
Published: April 2003

Atherosclerosis is the major cause of adult mortality in the developed world, and a significant contributor to atherosclerotic plaque progression involves smooth muscle cell recruitment to the intima of the vessel wall. Controversy currently exists on the exact origin of these recruited cells. Here we use sex-mismatched bone marrow transplant subjects to show that smooth muscle cells throughout the atherosclerotic vessel wall can derive from donor bone marrow. We demonstrate extensive recruitment of these cells in diseased compared with undiseased segments and exclude cell–cell fusion events as a cause for this enrichment. These data have broad implications for our understanding of the cellular components of human atherosclerotic plaque and provide a potentially novel target for future diagnostic and therapeutic strategies.
Isothermal reactions for the amplification of oligonucleotides
Authors: Van Ness Jeffrey , Van Ness Lori K. , Galas David J.
Published: April 2003

We have devised a class of isothermal reactions for amplifying DNA. These homogeneous reactions rapidly synthesize short oligonucleotides (8–16 bases) specified by the sequence of an amplification template. Versions of the reactions can proceed in either a linear or an exponential amplification mode. Both of these reactions require simple, constant conditions, and the rate of amplification depends entirely on the molecular parameters governing the interactions of the molecules in the reaction. The exponential version of the reaction is a molecular chain reaction that uses the oligonucleotide products of each linear reaction to create producers of more of the same oligonucleotide. It is a highly sensitive chain reaction that can be specifically triggered by given DNA sequences and can achieve amplifications of >10
6
-fold. Several similar reactions in this class are described here. The robustness, speed, and sensitivity of the exponential reaction suggest it will be useful in rapidly detecting the presence of small amounts of a specific DNA sequence in a sample, and a range of other applications, including many currently making use of the PCR.
Bacterial volatiles promote growth in
Arabidopsis
Authors: Ryu Choong-Min , Farag Mohamed A. , Hu Chia-Hui , Reddy Munagala S. , Wei Han-Xun , Paré Paul W. , Kloepper Joseph W.
Published: April 2003

Several chemical changes in soil are associated with plant growth-promoting rhizobacteria (PGPR). Some bacterial strains directly regulate plant physiology by mimicking synthesis of plant hormones, whereas others increase mineral and nitrogen availability in the soil as a way to augment growth. Identification of bacterial chemical messengers that trigger growth promotion has been limited in part by the understanding of how plants respond to external stimuli. With an increasing appreciation of how volatile organic compounds signal plants and serve in plant defense, investigations into the role of volatile components in plant–bacterial systems now can follow. Here, we present chemical and plant-growth data showing that some PGPR release a blend of volatile components that promote growth of
Arabidopsis thaliana
. In particular, the volatile components 2,3-butanediol and acetoin were released exclusively from two bacterial strains that trigger the greatest level of growth promotion. Furthermore, pharmacological applications of 2,3-butanediol enhanced plant growth whereas bacterial mutants blocked in 2,3-butanediol and acetoin synthesis were devoid in this growth-promotion capacity. The demonstration that PGPR strains release different volatile blends and that plant growth is stimulated by differences in these volatile blends establishes an additional function for volatile organic compounds as signaling molecules mediating plant–microbe interactions.
Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox
Authors: Lee Junghee , Ryu Hoon , Ferrante Robert J. , Morris Sidney M. , Ratan Rajiv R.
Published: April 2003

l
-Arginine is the only endogenous nitrogen-containing substrate of NO synthase (NOS), and it thus governs the production of NO during nervous system development as well as in disease states such as stroke, multiple sclerosis, Parkinson's disease, and HIV dementia. The “arginine paradox” refers to the dependence of cellular NO production on exogenous
l
-arginine concentration despite the theoretical saturation of NOS enzymes with intracellular
l
-arginine. Herein, we report that decreased availability of
l
-arginine blocked induction of NO production in cytokine-stimulated astrocytes, owing to inhibition of inducible NOS (iNOS) protein expression. However, activity of the promoter of the iNOS gene, induction of iNOS mRNA, and stability of iNOS protein were not inhibited under these conditions. Our results indicate that inhibition of iNOS activity by arginine depletion in stimulated astrocyte cultures occurs via inhibition of translation of iNOS mRNA. After stimulation by cytokines, uptake of
l
-arginine negatively regulates the phosphorylation status of the eukaryotic initiation factor (eIF2α), which, in turn, regulates translation of iNOS mRNA. eIF2α phosphorylation correlates with phosphorylation of the mammalian homolog of yeast GCN2 eIF2α kinase. As the kinase activity of GCN2 is activated by phosphorylation, these findings suggest that GCN2 activity represents a proximal step in the iNOS translational regulation by availability of
l
-arginine. These results provide an explanation for the arginine paradox for iNOS and define a distinct mechanism by which a substrate can regulate the activity of its associated enzyme.
Site-specific contributions to the pH dependence of protein stability
Authors: Tollinger Martin , Crowhurst Karin A. , Kay Lewis E. , Forman-Kay Julie D.
Published: April 2003

Understanding protein stability is a significant challenge requiring characterization of interactions within both folded and unfolded states. Of these, electrostatic interactions influence ionization equilibria of acidic and basic groups and diversify their pK
a
values. The pH dependence of the thermodynamic stability (ΔG
FU
) of a protein arises as a consequence of differential pK
a
values between folded and unfolded states. Previous attempts to calculate pH-dependent contributions to stability have been limited by the lack of experimental unfolded state pK
a
values. Using recently developed NMR spectroscopic methods, we have determined residue-specific pK
a
values for a thermodynamically unstable Src homology 3 domain in both states, enabling the calculation of the pH dependence of stability based on simple analytical expressions. The calculated pH stability profile obtained agrees very well with experiment, unlike profiles derived from two current models of electrostatic interactions within unfolded states. Most importantly, per-residue contributions to the pH dependence of ΔG
FU
derived from the data provide insights into specific electrostatic interactions in both the folded and unfolded states and their roles in protein stability. These interactions include a hydrogen bond between the Asp-8 side-chain and the Lys-21 backbone amide group in the folded state, which represents a highly conserved interaction in Src homology 3 domains.
Evidence for direct carotenoid involvement in the regulation of photosynthetic light harvesting
Authors: Ma Ying-Zhong , Holt Nancy E. , Li Xiao-Ping , Niyogi Krishna K. , Fleming Graham R.
Published: April 2003

Nonphotochemical quenching (NPQ) refers to a process that regulates photosynthetic light harvesting in plants as a response to changes in incident light intensity. By dissipating excess excitation energy of chlorophyll molecules as heat, NPQ balances the input and utilization of light energy in photosynthesis and protects the plant against photooxidative damage. To understand the physical mechanism of NPQ, we have performed femtosecond transient absorption experiments on intact thylakoid membranes isolated from spinach and transgenic
Arabidopsis thaliana
plants. These plants have well defined quenching capabilities and distinct contents of xanthophyll (Xan) cycle carotenoids. The kinetics probed in the spectral region of the S
1
→ S
n
transition of Xans (530–580 nm) were found to be significantly different under the quenched and unquenched conditions, corresponding to maximum and no NPQ, respectively. The lifetime and the spectral characteristics indicate that the kinetic difference originated from the involvement of the S
1
state of a specific Xan, zeaxanthin, in the quenched case.
A network of rice genes associated with stress response and seed development
Authors: Cooper Bret , Clarke Joseph D. , Budworth Paul , Kreps Joel , Hutchison Don , Park Sylvia , Guimil Sonia , Dunn Molly , Luginbühl Peter , Ellero Cinzia , Goff Stephen A. , Glazebrook Jane
Published: April 2003

We used a systematic approach to build a network of genes associated with developmental and stress responses in rice by identifying interaction domains for 200 proteins from stressed and developing tissues, by measuring the associated gene expression changes in different tissues exposed to a variety of environmental, biological, and chemical stress treatments, and by localizing the cognate genes to regions of stress-tolerance trait genetic loci. The integrated data set suggests that similar genes respond to environmental cues and stresses, and some may also regulate development. We demonstrate that the data can be used to correctly predict gene function in monocots and dicots. As a result, we have identified five genes that contribute to disease resistance in
Arabidopsis
.
An empty
Drosophila
stem cell niche reactivates the proliferation of ectopic cells
Authors: Kai Toshie , Spradling Allan
Published: April 2003

Stem cells are thought to reside in regulatory microenvironments (“niches”) generated by stable stromal neighbors. To investigate the significance of empty niches vacated by stem cell loss, we studied
Drosophila
ovarioles, which maintain two to three germ-line stem cells in a niche requiring adhesive stromal cap cells and
Decapentaplegic
signals. After experimentally emptying the germ-line stem cell niche, cap cell activity persists for several weeks. Initially, somatic inner germarium sheath cells enter the empty niche, respond to Dpp, but fail to divide. Subsequently, follicle cell progenitors, including somatic stem cells enter the niche, respond to Dpp, and proliferate as long as cap cells remain. Proliferation requires the normal
hedgehog
signal of the somatic stem cells as well as proximity to the niche. Thus, empty niches can persist, signal incoming cells, and support ectopic proliferation. Similar events may underlie some disease states.
Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients
Authors: Hodi F. Stephen , Mihm Martin C. , Soiffer Robert J. , Haluska Frank G. , Butler Marcus , Seiden Michael V. , Davis Thomas , Henry-Spires Rochele , MacRae Suzanne , Willman Ann , Padera Robert , Jaklitsch Michael T. , Shankar Sridhar , Chen Teresa C. , Korman Alan , Allison James P. , Dranoff Glenn
Published: April 2003

A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte–macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients.
Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia
in vitro
and on glucose utilization by brain
in vivo
Authors: Itoh Yoshiaki , Esaki Takanori , Shimoji Kazuaki , Cook Michelle , Law Mona J. , Kaufman Elaine , Sokoloff Louis
Published: April 2003

Neuronal cultures
in vitro
readily oxidized both D-[
14
C]glucose and
l
-[
14
C]lactate to
14
CO
2
, whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [
14
C]Glucose oxidation to
14
CO
2
varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [
14
C]lactate oxidation to
14
CO
2
only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvate/lactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity.
In vitro
dichloroacetate stimulated glucose and lactate oxidation to CO
2
and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons
in vivo
, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mg/kg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR
glc
). Dichloroacetate raised baseline lCMR
glc
throughout the brain and decreased the percent increases in lCMR
glc
evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.
Stabilization of β-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth
Authors: Haq Syed , Michael Ashour , Andreucci Michele , Bhattacharya Kausik , Dotto Paolo , Walters Brian , Woodgett James , Kilter Heiko , Force Thomas
Published: April 2003

β-Catenin is a transcriptional activator that regulates embryonic development as part of the Wnt pathway and also plays a role in tumorigenesis. The mechanisms leading to Wnt-induced stabilization of β-catenin, which results in its translocation to the nucleus and activation of transcription, have been an area of intense interest. However, it is not clear whether stimuli other than Wnts can lead to important stabilization of β-catenin and, if so, what factors mediate that stabilization and what biologic processes might be regulated. Herein we report that β-catenin is stabilized in cardiomyocytes after these cells have been exposed to hypertrophic stimuli in culture or
in vivo
. The mechanism by which β-catenin is stabilized is distinctly different from that used by Wnt signaling. Although, as with Wnt signaling, inhibition of glycogen synthase kinase-3 remains central to hypertrophic stimulus-induced stabilization of β-catenin, the mechanism by which this occurs involves the recruitment of activated PKB to the β-catenin-degradation complex. PKB stabilizes the complex and phosphorylates glycogen synthase kinase-3 within the complex, inhibiting its activity directed at β-catenin. Finally, we demonstrate via adenoviral gene transfer that β-catenin is both sufficient to induce growth in cardiomyocytes in culture and
in vivo
and necessary for hypertrophic stimulus-induced growth. Thus, in these terminally differentiated cells, β-catenin is stabilized by hypertrophic stimuli acting via heterotrimeric G protein-coupled receptors. The stabilization occurs via a unique Wnt-independent mechanism and results in cellular growth.