bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of a novel optically active nylon‐1 polymer: Anionic polymerization of L‐leucine methyl ester isocyanate
Authors: Sanda Fumio , Takata Toshikazu , Endo Takeshi
Published: April 2003

Synthesis and anionic polymerization of the isocyanate of L‐leucine methyl ester (LeuMI) were carried out. LeuMI was prepared by the reaction of L‐leucine methyl ester hydrochloride with phosgene. Anionic polymerization of LeuMI was carried out at –50°C in dimethyl‐formamide (DMF) using sodium methoxide, potassium tert‐butoxide, methyllithium, or sodium cyanide under a nitrogen atmosphere. The obtained polymers were insoluble in common organic solvents such as DMF, tetrahydrofuran, chloroform, and dimethyl sulfoxide, but were soluble in trifluoroacetic acid. Further, anionic copolymerization of LeuMI with n‐butyl isocyanate (BI) was also carried out to observe that the smaller the content of LeuMI unit in the copolymer was, the larger the specific rotation of the polymer. From the circular dichroic spectral analyses of the polymers it was confirmed that the capability of helix formation of poly (LeuMI) was smaller than poly(BI). The relaxation of the helical structure of the polymer in trifluoroacetic acid solution was observed, and the smaller the content of LeuMI unit in the copolymer was, the faster the relaxation of the helical structure. © 1995 John Wiley & Sons, Inc.
Styrene–maleic anhydride copolymerization through polar transition states in polar solvents
Authors: Lin Q. , Talukder M. , Pittman C. U.
Published: April 2003

Radical copolymerization of styrene (M1) and maleic anhydride (M2) was performed in highly polar, oxygen lone‐pair donor solvents (N, N‐dimethylformamide, N‐methylfor‐mamide) at high temperatures (135 and 145°C) and in strong π‐electron donor solvents (1,3‐dimethoxybenzene and 1,2,4‐trimethoxybenzene) at 60‐145°C. The corresponding reactivity ratios were evaluated by Fineman–Ross, Kelen Tüdos, and error‐in‐variables model (RREVM) methods. The reactivity ratios obtained (r1r2 < 1) show that alternating copolymers were produced. These results are best explained if the copolymerizations proceed through highly polarized radical transition states rather than styrene–maleic anhydride charge‐transfer complexes. Polar solvents stabilize highly polarized radical transition states thereby promoting alternating polymerization at higher temperatures than can be observed in nonpolar solvents. Donor solvents might also stabilize the electrophilic maleic anhydride radical more than the nucleophilic styryl radical thereby tending to depress k21 relative to k12. The copolymerizations were also studied in decalin (a nonpolar, nondonor solvent) at 60‐145°C. At lower temperatures alternating copolymers were combined. However, at temperatures > 120°C, random copolymers were obtained in decalin. Thus, in decalin, styrene–maleic anhydride charge‐transfer complexes are present at lower temperatures where they might play a role in alternation. In decalin the solvation of the polar transition states (relative to the macroradicals and monomers) does not favor copolymerization through such dipolar structures. Thus, at low temperatures growing chains could add to charge‐transfer complexes. However, at temperatures above 120°C the concentration of charge‐transfer complexes becomes so small that they can no longer be kinetically important contributions to the copolymerization. Thus, random copolymers with high styrene mole ratios are produced in decalin. The equilibrium constants for complex formation between maleic anhydride and both 1,3‐dimethoxybenzene and 1,2,4‐trimethoxybenzene were de‐termined in 1 : 1 (v/v) CCl4/CDCl3 using a technique based on changes in the NMR chemical shifts of the maleic anhydride protons. © 1995 John Wiley & Sons, Inc.
Chemoselective hydrosilations. I. Synthesis and photopolymerization of 1‐propenyl ether functionalized siloxanes
Authors: Crivello James V. , Yang Bo , Kim Whan‐Gi
Published: April 2003

The synthesis of 1‐propenyl ether‐functionalized siloxanes (PFS) has been achieved by the controlled, rhodium‐catalyzed, chemoselective hydrosilation of 1‐allyloxy‐4(1‐propen‐oxy) butane with various H‐functional siloxanes. It was shown that the hydrosilation pro‐ceeds exclusively at the allyl ether group of 1‐allyloxy‐4(1‐propenoxy) butane without par‐ticipation at the 1‐propenyl ether group. The photoinduced cationic polymerization of these monomers was studied using various analytical techniques and found to take place very rapidly. © 1995 John Wiley & Sons, Inc.
Mechanistic study of the reactivity of 3,4‐epoxycyclohexylmethyl 3′,4′‐epoxycyclohexancarboxylate in photoinitiated cationic polymerizations
Authors: Crivello James V. , Varlemann Ulrike
Published: April 2003

An investigation of the reactivity of the cycloaliphatic diepoxide, 3,4‐epoxycyclohexyl 3′, 4′‐epoxycycloexane carboxylate (I) in photoinitiated cationic polymerization was carried out with the aid of model compounds. It was shown that the presence of the ester group greatly retards the rate of polymerization of this bisepoxide. Molecular modeling studies indicate that the ester carbonyl group can interact in a number of ways with the initially formed protonated or alkylated oxiranium cation to give bicylic dialkoxycarbenium ions. These latter species are both more sterically hindered and less reactive than the oxiranium cation precursors and undergo propagation at a considerably reduced rate. Reactivity studies em‐ploying model compounds also showed that epoxy monomers that contain ester groups undergo polymerization at much slower rates than those in which the ester group is absent. © 1995 John Wiley & Sons, Inc.
Synthesis and characterization of poly(amide sulfonamide)s (PASAs)
Authors: Chan Winghong , Lam‐Leung Suei Yee , Ng Chingfai , Ding Junqi , Xi Shiping
Published: April 2003

New diamino monomers IIa–IIg were synthesized in a two‐step reaction sequence starting from p‐acetamidobenzenesulfonyl chloride. Solution polymerization of these monomers in DMAC with terephthaloyl or isophthaloyl chloride resulted in the formation of a series of 14 poly(amide sulfonamide)s (PASAs) in excellent yield (> 95%). The polymers have in‐trinsic viscosities of 0.32–1.11 dL g−1. Except for polymers IIIa−p and IIId‐p, all other PASAs were readily soluble in aprotic polar solvents including DMAC, DMF, and DMSO. Thermogravimetric analyses of the polymers showed moderate thermal stability with 10% weight loss being recorded in the range of 325–408°C. In addition, these polymers exhibit moderate chemical stabilities toward alkali, acidic, and chromic acid solution. © 1995 John Wiley & Sons, Inc.
Fundamental studies of grafting reactions in free radical copolymerization. I. A detailed kinetic model for solution polymerization
Authors: Huang Nai‐Jen , Sundberg Donald C.
Published: April 2003

Graft site initiation occurs by primary radical and/ or polymeric radical attack on the back‐bone polymer. The controlling mechanism is determined by the structure of the backbone and the activity of the free radicals. The efficiency of incorporating monomer into the graft chains depends upon the graft site initiation mechanism and the mode of polymer chain termination (recombination or disproportionation). A kinetic analysis results a series of uniquely different expressions describing the graft efficiency, ϕ corresponding to different combinations of graft site initiation and chain termination mechanisms. The dependency of ϕ upon monomer, initiator, and backbone concentrations is different from case to case. The complete kinetic model is capable of predicting reaction rate, graft efficiency, graft frequency, graft ratio, and molecular weight averages and distributions. Simulations are provided to compare predicted results with experimental data for two different systems which show contrasting mechanisms of graft site initiation and mode of termination. © 1995 John Wiley & Sons, Inc.
Enzyme‐catalyzed synthesis of aliphatic polyesters in organic media: Study of transesterification equilibrium shift and characterization of cyclic compounds
Authors: Mezoul G. , Lalot T. , Brigodiot M. , Maréchal E.
Published: April 2003

Enzyme‐catalyzed synthesis of aliphatic polyesters in organic media from methyl diesters and diols was carried out at stoechiometric ratio in the presence of supported lipases (li‐pozyme® and novozyme®). Two systems were studied to shift the thermodynamic equilibrium which limits the conversion. In the first one, the solution flows through a molecular sieve in which methanol is adsorbed. In the second one, methanol is eliminated by nitrogen bubbling. The system with nitrogen bubbling in hydrophobic solvents at 60°C works best when novozyme® is used as catalyst. Despite a high fractional conversion (p> 0.99), the number‐average molar mass is not very high (M̄;n = 3050 eq. PS). In relation to the nature of monomers, cycles with DP = 2–20 were characterized by chromatographic analyses and mass spectrometry. Their formation explains why high polycondensates cannot be obtained. © 1995 John Wiley & Sons, Inc.
Synthesis of novel macromonomers and telechelics of poly(2‐alkyl‐2‐oxazoline)s
Authors: Shimano Yasuo , Sato Kumiko , Kobayashi Shiro
Published: April 2003

Novel macromonomers and telechelics of poly(2‐alkyl‐2‐oxazoline) (PROZO) were syn‐thesized by utilizing termination of propagating species (2‐oxazolinium ions) in the living polymerization of 2‐alkyl‐2‐oxazoline (ROZO) with suitable nucleophiles. Two types of p‐vinylbenzyl–type macromonomers were obtained by terminating living PROZO with sodium p‐vinylbenzyl alkoxide or with sodium p‐vinylbenzyl mercaptide. The synthesis of telechelics having a functional group (SH, COOH) on both ends of PROZO was achieved by using a bis(2‐oxazolinium salt) initiator. The PROZO dithiol was synthesized by two methods: (1) termination of the living species on both ends with NaSH, and (2) aminolysis of PROZO bis(O‐ethyldithiocarbonate) given by treatment of the living PROZO with potassium O‐ethyldithiocarbonate. Termination of the living PROZO with the sodium salt of di‐t‐butyl malonate yielded a PROZO with di‐t‐butyl malonate moieties on both polymer ends, from which the PROZO dicarboxylic acid was derived via free tetracarboxylic acid. © 1995 John Wiley & Sons, Inc.
Characterization and comparison of poly(aryl ether ketone)s containing dibenzoylbiphenyl moieties: Effects of changes in biphenyl substitution pattern on thermal and mechanical properties
Authors: Moulinié Pierre , Paroli Ralph M. , Wang Zhi Yuan
Published: April 2003

A monomer, 3,3′‐bis (4‐fluorobenzoyl) biphenyl, was prepared in high yield in two steps from inexpensive 3‐chlorobenzoyl chloride and fluorobenzene, and polymerized by nucleophilic displacement reaction with various bisphenol monomers in tetramethylene sulfone to produce a series of high molecular weight poly(aryl ether ketone)s containing 3,3′‐dibenzoylbiphenyl (DBBP) moieties. The spectroscopic, thermal, and thermomechanical properties of these polymers and related isomeric polymers having 2,2′‐and 4,4′‐DBBP units were determined and compared to study the effects of changes in the substitution pattern of the biphenyl unit. Except for the 2,2′‐DBBP series of polymers, Tgs were found to increase with increasing linearity of the DBBP unit. The 2,2′‐DBBP series of polymers had exceptionally high Tgs due to the sterically restricted motions in the biphenyl unit caused by the 2,2′‐substitution. In addition, they also showed evidence for torsion with the 2,2′‐DBBP unit, whereas in other isomeric polymers the DBBP units are believed to be relatively coplanar. Thermal stabilities and tensile moduli for these polymers proved to be independent of substitution patterns. © 1995 John Wiley & Sons, Inc.
Olefin terpolymerizations. II. 4‐vinylcyclohexene and cyclooctadiene
Authors: Marques Maria , Yu Zhengtian , Rausch Marvin D. , Chien James C. W.
Published: April 2003

4‐Vinylcyclohexene (VCH) and cyclooctadiene (COD) were investigated as termonomers in EPDM (ethylene/propylene/diene) synthesis by using rac‐ethylenebis (1‐η5‐indenyl) zir‐conium dichloride (1) as a catalyst precursor. Homopolymerizations of VCH, vinylcycloh‐exane and cyclohexene were compared. The parameter Kπκp, which is the apparent rate constant for Ziegler‐Natta polymerization, is about the same for VCH and vinylcyclohexanebut is 10 times smaller for cyclohexene. Therefore, the linear olefinic double bond is more active than the cyclic internal double bond. VCH reduces ethylene polymerization rate but not propylene polymerization rate in copolymerizations. In terpolymerizations, VCH tends to suppress ethylene incorporation especially at elevated polymerization temperature and Lowers the polymer MW by about two‐fold. COD has very low activity as a termonomer. © 1995 John Wiley & Sons, Inc.
Preparation of polyamides derived from 1,6‐diamantane dicarboxylic chloride by solution polycondensation and interfacial polycondensation
Authors: Chern Yaw‐Terng , Fang Jea‐Shih , Kao Shen C.
Published: April 2003

1,6‐Diamantane dicarboxvlic acyl chloride (I) was used as a monomer with various aromatic diamines to synthesize polyamides by interfacial polycondensation and solution polycon‐densation. The polyamides prepared by interfacial polycondensation had inherent viscosities between 0.38 and 0.15 dL/g. The polyamides prepared by solution polycondensation had inherent viscosities between 0.62 and 0.25 dL/g. The polyamides IIIa prepared by solution polycondensation showed the main melting transition at 380°C by dynamic mechanical analysis. In addition, it was quite temperature‐stable and maintained good mechanical properties (G′⋐108 Pa) up to high temperatures close to the main transition well above 350°C. The polyamide IIIA had a tensile strength of 35 MPa, elongations to break of 10%, and initial modulus of 0.8 GPa. Some of the polyamides were soluble in NMP, DMAc, and DMSO, depending on soft segment moiety of diamine (II). The polyamides prepared by interfacial polycondensation have a greater tendency to form crystal than those prepared by solution polycondensation, as evidenced by x‐ray diffraction studies. These polyamides had glass transition temperatures in the 270–300°C range, and 5% weight loss temperatures up to 435°C in nitrogen. © 1995 John Wiley & Sons, Inc.
Novel copolyesters containing naphthalene structure. II. Copolyesters prepared from 2,6‐dimethyl naphthalate, 1,4‐dimethyl terephthalate, and ethylene glycol
Authors: Lu Tsu‐Shang , Sun Yih‐Min , Wang Chun‐Shan
Published: April 2003

Copolyesters containing rigid segments (naphthalene and terephthalene) and flexible seg‐ments (aliphatic diol) structure were synthesized from DMN/DMT/EG (2,6‐dimethyl naphthalate/1,4‐dimethyl terephthalate/ethylene glycol) ternary monomers with various mole ratios. Copolyesters having intrinsic viscosities of 0.52–0.65 dL/g were obtained by melt polycondensation in the presence of metallic catalysts. The effect of reaction tem‐perature and time on the formation of the copolyesters was investigated to obtain an op‐timum condition for copolyester manufacturing. The optimum condition for PNT (poly‐ethylene naphthalate terephthalate) copolyester manufacturing is the transesterification under nitrogen atmosphere for 4 h at a temperature of 185±2°C followed by polymerization under 2 mm Hg for 2 h at a temperature of 280°C. Most copolyesters have better solubilities than poly(ethylene naphthalate) (PEN) and poly(ethylene terephthalate) (PET) in various solvents. The effect of the starting mole ratio of DMN, DMT, and EG on the thermal properties of the resulted copolyesters was also investigated using differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). Glass transition temperatures of copolyesters were in the range of 70.7–115.2°C, and 10% weight loss in nitrogen were all above 426°C. © 1995 John Wiley & Sons, Inc.
Pyrolysis chemical ionization mass spectrometry of cellulose ethers
Authors: Arisz P. W. , Boon J. J.
Published: April 2003

Pyrolysis ammonia chemical ionization (PyCI) mass spectrometry was performed on hy‐droxyethyl‐, hydroxypropyl‐,methyl‐, hydroxypropylmethyl‐, and ethylhydroxyethyl cel‐luloses. The mass peaks in the PyCI mass spectra of these cellulose ethers could be assigned to the ions of pyrolytic dissociation products which form via the [2 + 2 + 2] cycloreversion and the Ei elimination pyrolysis pathway. Structural information about the residual amount of nonderivatized cellulose, the relative chain length distributions of the substituents in hydroxyalkyl celluloses, and the end‐capping of hydroxyalkyl substituents by alkyl groups in the mixed cellulose ethers is obtained. Interference of secondary pyrolysis products in the PyCI mass spectra is found to be of minor importance, especially in the lower mass regions. © 1995 John Wiley & Sons, Inc.
Amine‐quinone polyurethanes. I. Preparation of polyurethane block copolymers containing 2,5–bis(N‐2‐hydroxyethyl‐N‐methylamino)‐1,4–benzoquinone diol monomer
Authors: Nikles David E. , Liang Jeng‐Li , Cain Jason L. , Chacko Antony P. , Webb Russell I. , Belmore Ken
Published: April 2003

The amine‐quinone monomer, 2,5–bis(N‐2‐hydroxyethyl‐N‐methylamino)‐1,4‐benzoqui‐none (AQM‐1), was prepared by the multiple‐step condensation of 2‐(N‐methylam‐ino)ethanol with benzoquinone in the presence of oxygen. This crystalline monomer was used to prepare a series of amine‐quinone polyurethanes by condensation polymerization, either in the melt or in solution (THF or DMF), with a diisocyanate (MDI, TDI, or IPDI) and an oligomeric diol [poly(caprolactone) or poly(1,2‐butylene glycol)]. The amine‐quinone functional group was stable under the polymerization conditions, and was incorporated into the main chain, giving red‐brown polyurethanes that had molecular weights in the range of 11,000–90,000 and were soluble in THF, MEK, DMF, and DMSO. The thermal properties were consistent with a two‐phase morphology with an amorphous soft segment, containing the oligomeric diol, and a microcrystalline hard segment, containing AQM‐1. The polymers having a low hard segment content (<50%) were rubbery (soft segment Tg <−25°C); polymers having a high hard segment content (>50%) were thermoplastic (hard segment Tg>150°C). © 1995 John Wiley & Sons, Inc.
Redox polymerization process: An efficient tool for the synthesis of block copolymers
Authors: Nagarajan Soundappan , Srinivasan Kalathur Sabdham Vangepuram
Published: April 2003

The synthesis of poly(acrylonitrile)‐block‐poly‐(ethylene glycol)‐block‐poly(acrylonitrile) copolymers has been carried out using a redox system consisting of ceric ion and poly(ethylene glycol)s of various molecular weights in aqueous medium. The generation of intermediate radicals in the redox process has been confirmed by ESR spectroscopy and the polymerization progressing through ‘blocking from’ mechanism has been postulated. The formation of the block copolymers has been confirmed by chemical tests and fractional precipitation technique as well as by FT‐IR and FT‐NMR [1H and 13C–(1H)] spectroscopic techniques. The triblock nature of the block copolymers has been ascertained through the cleavage of ether linkage of the PEG segment. TG/DTA studies of the block copolymers with PEG molecular weights of 1000 and above revealed two‐stage decomposition, while their DSC traces exhibited a shift in the melting peak of PEG. GPC investigations of the block copolymers manifested a high homogeneity with unimodal distribution of molecular weights. SEM studies indicated significant changes in the morphological characteristics of the block copolymers. © 1995 John Wiley & Sons, Inc.
LuCaP 35: A new model of prostate cancer progression to androgen independence
Authors: Corey Eva , Quinn Janna E. , Buhler Kent R. , Nelson Peter S. , Macoska Jill A. , True Lawrence D. , Vessella Robert L.
Published: April 2003

Background

Generation of suitable in vivo models is critical for understanding of processes associated with development and progression of prostate cancer (CaP).

Methods

Lymph nodes containing metastatic androgen‐independent CaP were implanted into athymic mice. A xenograft designated LuCaP 35 and its hormone‐independent variant LuCaP 35V were established and characterized.

Results

LuCaP 35 is an androgen‐sensitive, prostate‐specific antigen (PSA)‐producing xenograft. It expresses the wild‐type androgen receptor and exhibits deletions in chromosome 8p, but not in chromosome 10. The response of LuCaP 35 to androgen ablation is similar to that observed in man. Using recurring LuCaP 35 tumors we have also established an androgen‐insensitive variant of LuCaP 35.

Conclusions

The availability of hormone‐dependent and ‐independent variants of LuCaP 35, which exhibit many properties analogous to those of CaP in man, provides an excellent model system to study the processes associated with development of androgen independence and to evaluate new treatment modalities. Prostate 55: 239–246, 2003. © 2003 Wiley‐Liss, Inc.
Suppression of LNCaP prostate cancer xenograft tumors by a prostate‐specific protein tyrosine phosphatase, prostatic acid phosphatase
Authors: Igawa Tsukasa , Lin Fen‐Fen , Rao Prathibha , Lin Ming‐Fong
Published: April 2003

Background

Although the molecular mechanism of androgen‐independent prostate cancer growth and progression has been gradually elucidated, there is limited effective treatment for this prevalent disease. Human prostatic acid phosphatase (PAcP), a major protein tyrosine phosphatase in prostate epithelium, plays a critical role in regulating the growth of prostate cancer cells. In prostate carcinomas, the expression of cellular PAcP decreases. To explore directly the possible therapeutic potential of cellular PAcP, we investigated the suppression effect of PAcP by utilizing cDNA direct intratumoral administration in androgen‐independent LNCaP xenograft tumors.

Methods

An androgen‐independent LNCaP cell model (C‐33 and C‐81 cells) and stable subclones of PAcP cDNA‐transfected C‐81 cells (LNCaP‐23 and LNCaP‐34 cells) were used for the experiments. We examined the growth property and expression of PAcP and c‐ErbB‐2 of these different LNCaP cells in vitro and in vivo. We subsequently investigated the growth suppression effect of PAcP cDNA intratumoral injection in pre‐established C‐81 xenograft tumors, and analyzed the expression of PAcP, prostate‐specific antigen (PSA), proliferating cell nuclear antigen (PCNA), and c‐ErbB‐2 in the tumors by immunohistochemistry and Western blotting.

Results

The different LNCaP cells exhibited different growth property and tumorigenicity, both in cell culture and xenograft. Biochemical characterizations revealed that the level of cellular PAcP correlated negatively with the growth property of different LNCaP cells, while the level of tyrophosphorylated c‐ErbB‐2 had an inverse correlation with cellular PAcP. The single intratumoral administration of the wild type PAcP cDNA showed a significant suppression effect on C‐81 xenograft tumor growth, compared to vector alone‐injected control (P <0.05). In the tumors injected with this PAcP cDNA, the PAcP expression was detected 1 week (wk) after injection, but was undetectable at 6 wk, which inversely correlated with the level of tyrophosphorylated c‐ErbB‐2 and the degree of cell proliferation indicated by PCNA staining.

Conclusions

Our results clearly demonstrated that cellular PAcP has a suppression effect on the growth of androgen‐independent LNCaP xenograft tumors. This effect occurs at least partly through the dephosphorylation of c‐ErbB‐2 by PAcP, the prostate‐specific protein tyrosine phosphatase. The data indicates that human PAcP could be utilized in the corrective gene therapy for a subgroup of androgen‐independent human prostate cancer cells that lack cellular PAcP expression. Prostate 55: 247–258, 2003. © 2003 Wiley‐Liss, Inc.
Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice
Authors: Yoshimoto Tomohiro , Min Booki , Sugimoto Takaaki , Hayashi Nobuki , Ishikawa Yuriko , Sasaki Yuki , Hata Hitomi , Takeda Kazuyoshi , Okumura Ko , Van Kaer Luc , Paul William E. , Nakanishi Kenji
Published: April 2003

Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4+ T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d−/− mice that lack natural killer T (NKT) cells and in class II−/− mice that lack conventional CD4+ T cells. However, class II−/− mice reconstituted with conventional CD4+ T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)α chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4+ T cells express low levels of IL-18Rα and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4+ T cells are essential for B cell IgE responses after the administration of IL-18. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4+ T cells demonstrate their helper function in the presence of NKT cells.
In Vivo Survival and Homeostatic Proliferation of Natural Killer Cells
Authors: Prlic Martin , Blazar Bruce R. , Farrar Michael A. , Jameson Stephen C.
Published: April 2003

While the specificity and development of natural killer (NK) cells have been intensely studied, little is known about homeostasis of the mature NK population. Here we show that mouse NK cells undergo homeostatic proliferation when transferred into NK-deficient Rag−/− γC−/− hosts. Normal NK functional activity is maintained during this process, although there are some changes in NK phenotype. Using cell sorting, we demonstrate that mature (Mac-1hi) NK cells undergo homeostatic proliferation in an NK-deficient environment, yet immature (Mac-1lo) NK cells also proliferate in such hosts. We find that mature NK cells survive but do not proliferate in hosts which possess an endogenous NK pool. However, we go on to show that mature NK survival is critically dependent on interleukin (IL)-15. Surprisingly, NK survival is also compromised after transfer of cells into IL-15Rα−/− mice, implying that IL-15 responsiveness by bystander cells is critical for NK maintenance. These data imply that, similar to T cells, homeostasis of the NK pool is much more dynamic than previously appreciated and this may be relevant to manipulation of NK cells for therapeutic purposes.
Mokken Scale Analysis: Between the Guttman Scale and Parametric Item Response Theory
Authors: van Schuur Wijbrandt H.
Published: April 2003

This article introduces a model of ordinal unidimensional measurement known as Mokken scale analysis. Mokken scaling is based on principles of Item Response Theory (IRT) that originated in the Guttman scale. I compare the Mokken model with both Classical Test Theory (reliability or factor analysis) and parametric IRT models (especially with the one-parameter logistic model known as the Rasch model). Two nonparametric probabilistic versions of the Mokken model are described: the model of Monotone Homogeneity and the model of Double Monotonicity. I give procedures for dealing with both dichotomous and polytomous data, along with two scale analyses of data from the World Values Study that demonstrate the usefulness of the Mokken model.
On the Overreport Bias of the National Election Study Turnout Rate
Authors: McDonald Michael P.
Published: April 2003

Consumers of the National Election Study (NES) should be concerned if the survey has a bias that is increasing with time. A recent article by Barry Burden claims that for presidential elections, there is an increasing overreport bias, or turnout gap, between the NES turnout rate and the observed turnout rate caused by declining NES response rates. I show that the increasing turnout gap is an artifact of the universes these two turnout rates are based on. Reconciling the two universes shows no systematic increase of the reconciled turnout gap in presidential elections from 1948 to 2000, and furthermore demonstrates that the post-1976 rise in NES response rates (until 2000) is rewarded in a lower turnout gap. In addition, I offer another theory to explain the turnout gap. If respondents have an equal propensity to misreport that they voted when they did not, as turnout declines, the number of nonvoter respondents increases and so does the turnout gap. I show that in multivariate analysis this theory outperforms Burden's response rate driven theory, though neither theory reaches statistical significance.
Estimation of Models with Beta-Distributed Dependent Variables: A Replication and Extension of Paolino's Study
Authors: Buckley Jack
Published: April 2003

This note replicates and extends Paolino's discussion (2001, Political Analysis 9:325–346) on the estimation of models with beta-distributed dependent variables in two ways. First, it introduces an easy-to-use program for estimating the model using Stata. Second, it presents a Bayesian estimator for beta variables based on Paolino's model. Results are compared to those in the original article.
Vibrating Wire Loop and the Bohr Model
Authors: Bloom Danning , Bloom Dan W.
Published: April 2003

PASCO scientific1 has designed a vibration apparatus that includes a mechanical driver used to excite vibrations in various systems. One of these is a circular wire loop, which PASCO suggests can be used as a visual representation of the Bohr model of the hydrogen atom. In this paper we investigate the similarity between the wire loop and the Bohr atom.
Rotational Collision Apparatus for Indoor Egg Drops
Authors: Halada Richard
Published: April 2003

Our units about momentum and energy are richly illustrated with applications to car crashes and explanations of such safety features as airbags and crumple zones. The main lab exercise, however, is an egg crash (car insurance rates being so much higher). Fairly standard rules apply: Students must devise an “egg-protection package” that will keep a teacher-supplied egg intact through two successive impacts. After the test, they must hand in a written analysis of the specific physics principles they employed, modifications they would make after seeing their project's actual performance, and suggestions for applying their protection system to auto safety.
Quantitative Ischemia Detection During Cardiac Magnetic Resonance Stress Testing by Use of FastHARP
Authors: Kraitchman Dara L. , Sampath Smita , Castillo Ernesto , Derbyshire John A. , Boston Raymond C. , Bluemke David A. , Gerber Bernhard L. , Prince Jerry L. , Osman Nael F.
Published: April 2003

Background—

Because ECG alterations caused by ischemia cannot be reliably detected in the high-field MRI environment, detection of wall motion abnormalities is often used to ensure patient safety during stress testing. However, an experienced observer is needed to detect these abnormalities. In this study, we investigate the use of fast harmonic phase (FastHARP) MRI for the quantitative, operator-independent detection of the onset of ischemia during acute coronary occlusion.

Methods and Results—

Eight mongrel dogs underwent an acute 2-minute closed-chest coronary artery occlusion while continuous FastHARP images were acquired. Full regional wall strain was determined every other heartbeat in a single short-axis imaging slice. After 5 minutes of reperfusion, a second 2-minute ischemic episode was induced during the acquisition of conventional cine wall-motion images. The time at which ECG alterations were observed during the first ischemic period was recorded. The time from occlusion to the detection of ischemia, based on a consensus of 2 blinded observers, was determined for MRI. No significant ischemia was present in 2 animals. In the remaining animals, the onset of ischemia was detected significantly earlier by FastHARP than by cine MRI (9.5±5 versus 33±14 seconds,
P
<0.01). HARP ischemia detection preceded ECG changes, on average, by 54 seconds.

Conclusions—

The rapid acquisition and detection of induced ischemia with FastHARP MRI shows promise as a nonsubjective method to diagnose significant coronary lesions during MR stress testing.
Constitutively Active Adenosine Monophosphate–Activated Protein Kinase Regulates Voltage-Gated Sodium Channels in Ventricular Myocytes
Authors: Light Peter E. , Wallace Catriona H.R. , Dyck Jason R.B.
Published: April 2003

Background—

Some PRKAG2 mutations in the human gene encoding for the γ-subunit of the adenosine monophosphate–activated protein kinase (AMPK) recently have been shown to cause rhythm disturbances (often fatal) in affected patients.

Methods and Results—

Rat ventricular myocytes were infected with an adenoviral vector designed to express a truncated constitutively active mutant (T172D) of the AMPK α
1
-subunit (CA-AMPK). The human cardiac sodium channel hH1 and CA-AMPK were also coexpressed in a mammalian cell line. Patch-clamp techniques were used to measure myocyte action potentials and recombinant hH1 sodium channel currents. Our results demonstrate that action potential duration is significantly prolonged in myocytes expressing the CA-AMPK construct, leading to the production of potentially arrhythmogenic early afterdepolarizations. Recombinant sodium channel current analysis revealed that expression of CA-AMPK significantly slowed open-state inactivation and shifted the voltage-activation curve in a hyperpolarizing direction.

Conclusion—

We propose that sodium channels may be substrates for AMPK, possibly contributing to the observed arrhythmogenic activity in patients with some PRKAG2 mutations.
Effect of Rosiglitazone Treatment on Soluble CD40L in Patients With Type 2 Diabetes and Coronary Artery Disease
Authors: Marx Nikolaus , Imhof Armin , Froehlich Johannes , Siam Laila , Ittner Jochen , Wierse Gerhard , Schmidt Arnold , Maerz Winfried , Hombach Vinzenz , Koenig Wolfgang
Published: April 2003

Background—

Interaction of CD40L with its receptor CD40 is critically involved in inflammatory cell activation in atherogenesis. In addition, serum levels of soluble CD40L are elevated in acute coronary syndromes and have been associated with increased cardiovascular risk in healthy subjects, thus making sCD40L an intriguing target to modulate the inflammatory response in the vasculature. PPARγ-activating thiazolidinediones, novel insulin-sensitizing antidiabetic agents, have recently been shown to exhibit antiinflammatory effects in the vessel wall. To examine whether thiazolidinedione treatment might modulate serum levels of sCD40L in high-risk patients, we performed a randomized, placebo-controlled, single-blinded trial to assess the effect of rosiglitazone on sCD40L levels in patients with type 2 diabetes and coronary artery disease (CAD).

Methods and Results—

Thirty-nine patients with diabetes and angiographically proven CAD were randomized to receive rosiglitazone (4 mg BID) or placebo for 12 weeks. Baseline parameters did not significantly differ between groups. Rosiglitazone treatment, but not placebo, significantly reduced sCD40L serum levels within the first 2 weeks by 8.1% (17.1 to −32.7) (median percentage [interquartile range];
P
<0.05 compared with baseline), further decreasing it by 18.4% (−5.0 to −33.1) after 6 weeks (
P
<0.05 compared with baseline), and by 27.5% (8.2 to −70.5) after 12 weeks (
P
<0.05 compared with baseline and with 2 weeks of treatment).

Conclusion—

Treatment with the PPARγ-activating thiazolidinedione rosiglitazone reduces sCD40L serum levels in patients with type 2 diabetes and CAD. These data support an antiinflammatory and potentially antiatherogenic effect of thiazolidinediones.
TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome–positive leukemia cells
Authors: Uno Kanako , Inukai Takeshi , Kayagaki Nobuhiko , Goi Kumiko , Sato Hiroki , Nemoto Atsushi , Takahashi Kazuya , Kagami Keiko , Yamaguchi Noriko , Yagita Hideo , Okumura Ko , Koyama-Okazaki Toshiko , Suzuki Toshio , Sugita Kanji , Nakazawa Shinpei
Published: April 2003

Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)–positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia–derived and 7 acute leukemia–derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor κB inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain–like interleukin-1–converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL–specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.
Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells
Authors: Waldburger Jean-Marc , Rossi Simona , Hollander Georg A. , Rodewald Hans-Reimer , Reith Walter , Acha-Orbea Hans
Published: April 2003

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV−/− mice. Medullary thymic epithelial cells (mTECs) are also MHCII− in pIV−/− mice. Bone marrow–derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV−/− mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4+ thymocytes in pIV−/− mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV−/−mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4+T-cell population of pIV−/− mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the Vβ repertoire of the residual CD4+ T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common γ chain (CD132) or common β chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.
Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses
Authors: Li Henry Y. , Appelbaum Frederick R. , Willman Cheryl L. , Zager Richard A. , Banker Deborah E.
Published: April 2003

The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a product of this pathway, HMG-CoA reductase inhibitors (statins) are used to treat hypercholesterolemia. Statins are also toxic to several malignancies, including acute myeloid leukemia (AML). Although this toxicity has been attributed to the inhibition of Ras/Rho isoprenylation, we have previously shown that statin toxicity in primary AML cells (AMLs) does not correlate with Ras isoprenylation or with activating Ras mutations. In other studies, we have shown that hypoxic and oxidant injuries induce cholesterol increments in renal tubule cells and that statins sensitize these cells to injury by blocking protective cholesterol responses. We now demonstrate that exposing particular AMLs to radiochemotherapy induces much greater cellular cholesterol increments than those seen in similarly treated normal bone marrow. Treatment of these AMLs with mevastatin or zaragozic acid (which inhibits cholesterol synthesis but not isoprenoid synthesis) attenuates the cholesterol increments and sensitizes cells to radiochemotherapy. The extent of toxicity is affected by the availability of extracellular lipoproteins, further suggesting that cellular cholesterol is critical to cell survival in particular AMLs. Because zaragozic acid does not inhibit isoprenoid synthesis, these data suggest that cholesterol modulation is an important mechanism whereby statins exert toxic effects on some AMLs and that cholesterol modulators may improve therapeutic ratios in AML by impacting cholesterol-dependent cytoresistance.
Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes
Authors: Campàs Clara , López José Manuel , Santidrián Antonio F. , Barragán Montserrat , Bellosillo Beatriz , Colomer Dolors , Gil Joan
Published: April 2003

Acadesine, 5-aminoimidazole-4-carboxamide (AICA) riboside, induced apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells in all samples tested (n = 70). The half-maximal effective concentration (EC50) for B-CLL cells was 380 ± 60 μM (n = 5). The caspase inhibitor Z-VAD.fmk completely blocked acadesine-induced apoptosis, which involved the activation of caspase-3, -8, and -9 and cytochrome c release. Incubation of B-CLL cells with acadesine induced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), indicating that it is activated by acadesine. Nitrobenzylthioinosine (NBTI), a nucleoside transport inhibitor, 5-iodotubercidin, an inhibitor of adenosine kinase, and adenosine completely inhibited acadesine-induced apoptosis and AMPK phosphorylation, demonstrating that incorporation of acadesine into the cell and its subsequent phosphorylation to AICA ribotide (ZMP) are necessary to induce apoptosis. Inhibitors of protein kinase A and mitogen-activated protein kinases did not protect from acadesine-induced apoptosis in B-CLL cells. Moreover, acadesine had no effect on p53 levels or phosphorylation, suggesting a p53-independent mechanism in apoptosis triggering. Normal B lymphocytes were as sensitive as B-CLL cells to acadesine-induced apoptosis. However, T cells from patients with B-CLL were only slightly affected by acadesine at doses up to 4 mM. AMPK phosphorylation did not occur in T cells treated with acadesine. Intracellular levels of ZMP were higher in B-CLL cells than in T cells when both were treated with 0.5 mM acadesine, suggesting that ZMP accumulation is necessary to activate AMPK and induce apoptosis. These results suggest a new pathway involving AMPK in the control of apoptosis in B-CLL cells and raise the possibility of using acadesine in B-CLL treatment.
Macrophage inflammatory protein 1-alpha (MIP-1α) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells
Authors: Lentzsch Suzanne , Gries Margarete , Janz Martin , Bargou Ralf , Dörken Bernd , Mapara Markus Y.
Published: April 2003

Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1α) is crucially involved in the development of osteolytic bone lesions in multiple myeloma (MM). The current study was designed to determine the direct effects of MIP-1α on MM cells. Thus, we were able to demonstrate that MIP-1α acts as a potent growth, survival, and chemotactic factor in MM cells. MIP-1α–induced signaling involved activation of the AKT/protein kinase B (PKB) and the mitogen-activated protein kinase (MAPK) pathway. In addition, inhibition of AKT activation by phosphatidylinositol 3- kinase (PI3-K) inhibitors did not influence MAPK activation, suggesting that there is no cross talk between MIP-1α–dependent activation of the PI3-K/AKT and extracellular-regulated kinase (ERK) pathway. Our data suggest that besides its role in development of osteolytic bone destruction, MIP-1α also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and provide evidence that MIP-1α might play a pivotal role in the pathogenesis of MM.
Reconstitution of NK cell receptor repertoire followingHLA-matched hematopoietic cell transplantation
Authors: Shilling Heather G. , McQueen Karina L. , Cheng Nathalie W. , Shizuru Judith A. , Negrin Robert S. , Parham Peter
Published: April 2003

Interactions between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands influence development of natural killer (NK) cell repertoire and response to infection, cancer, and allogeneic tissue. As KIRs and HLA class I molecules are highly polymorphic, clinical allogeneic hematopoietic cell transplantation is predicted to frequently involve KIRmismatch, and thus to provide a unique system for study of human NK cell receptor repertoire development. Eighteen leukemia patients undergoing HLA-matched transplantation and their donors were analyzed for KIR genotype. Ten of 13HLA-identical donor-patient pairs were KIRmismatched and 3 were matched; all HLA-matched unrelated pairs were KIR mismatched. Reconstitution of recipient NK cell repertoire following transplantation was examined using flow cytometry and monoclonal antibodies specific for KIR and CD94:NKG2A. These data form 3 groups. Six to 9 months after transplantation, 8 patients (group 1) reconstituted an NK cell repertoire resembling that of their donor, and forKIR-mismatched transplants, distinct from the recipient before transplantation. In the first year after transplantation, 5 patients (group 2) exhibited a generally depressed frequency of KIR-expressing NK cells and concomitant high frequency of CD94:NKG2A expression. By 3 years after transplantation, the frequency of KIR-expressing NK cells had increased to donor values, in the 3 patients from group 2 analyzed for this period. The remaining 5 patients experienced severe clinical complications following transplantation and displayed unique features in their NK cell receptor reconstitution. These results demonstrate that a majority ofHLA-matched hematopoietic cell transplantations involveKIR mismatch and reveal differences in NK cell repertoire having potential impact for immune responsiveness and transplantation outcome.