bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective Total Synthesis of Octalactin A Using Asymmetric Aldol Reactions and a Rapid Lactonization To Form a Medium‐Sized Ring
Authors: Shiina Isamu , Hashizume Minako , Yamai Yu‐suke , Oshiumi Hiromi , Shimazaki Takahisa , Takasuna Yu‐ji , Ibuka Ryoutarou
Published: August 2005

Octalactin A, an antitumor agent containing an eight‐membered lactone moiety, has been stereoselectively prepared by means of enantioselective aldol reactions of selected silyl enolates with achiral aldehydes, promoted by a chiral SnII complex. The medium‐sized lactone part was effectively constructed by way of a new and rapid mixed‐anhydride lactonization using 2‐methyl‐6‐nitrobenzoic anhydride (MNBA) with a catalytic amount of 4‐(dimethylamino)pyridine (DMAP) or 4‐(dimethylamino)pyridine 1‐oxide (DMAPO). The use of only 5 mol % of DMAP or 2 mol % of DMAPO rapidly promoted formation of the medium‐sized ring of the octalactin, demonstrating the remarkable efficiency of the new lactonization protocol.
Testing association and linkage using affected‐sib‐parent study designs
Authors: Millstein Joshua , Siegmund Kimberly D. , Conti David V. , Gauderman W. James
Published: August 2005

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity‐by‐descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85–97), and an association test comparable to the Family‐Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211–223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Genet. Epidemiol. © 2005 Wiley‐Liss, Inc.
Acid‐induced bioactive titania surface
Authors: Zhao Xiaobing , Liu Xuanyong , Ding Chuanxian
Published: August 2005

Nano‐ and conventional‐TiO2 powders were deposited onto titanium alloy using atmospheric plasma spraying technology. As‐sprayed titania coatings were treated by H2SO4 and HCl solutions at room temperature for 24 h, and the bioactivity was evaluated by simulated body fluid tests. Measured X‐ray diffraction patterns indicated that as‐sprayed titania coatings obtained from both nano and conventional powders were composed of primary rutile as well as a small quantity of anatase and Ti3O5. The surface of as‐sprayed coatings prepared from the conventional powder was rougher than that from nanopowder. After immersion in simulated body fluid for 2 weeks, both acid‐treated nano‐ and titania coatings have induced carbonate‐containing hydroxyapatite to form on the surfaces. However, this phenomenon did not appear on the surface of as‐sprayed nano‐ and conventional‐titania coatings. The results obtained indicated that the bioactivity of plasma sprayed titania coatings was improved by the acid treatment and had nothing to do with phase composition and particle size of the original TiO2 powders. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Quantitative analysis of fibrosis formation on the microcapsule surface with the use of picro‐sirius red staining, polarized light microscopy, and digital image analysis
Authors: Zhang Hua'an , Sun Lin , Wang Wei , Ma Xiaojun
Published: August 2005

Transplantation of microencapsulated cells shows potential to treat a variety of diseases. To improve the quality of microcapsules, efficient methods need to be established and standardized for the evaluation of biocompatibility of microcapsules. To this end, a microscopical method was developed to analyze quantitatively the degree of fibrotic overgrowth (FO), which serves as the index of biocompatibility. In this method, sections were stained with picro‐sirius red and illuminated with a polarized light microscope. The images were digitized with the use of a computer‐video system in which collagenous content was depicted by gray levels 1 to 255. Both the area of collagen and the thickness of FO were examined. The ratio of Type I/Type III collagen and the thickness were used as indexes of the degree of FO. The data showed that the ratio of Type I/Type III collagen and the thickness increased with time, and FO was not significant 4 weeks after transplantation. In comparison, this new method is more efficient to evaluate FO. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Needle catheter jejunostomy at esophagectomy for cancer
Authors: Sica Giuseppe S. , Sujendran Vijay , Wheeler James , Soin Bob , Maynard Nicholas
Published: August 2005

Important physiological changes occur after major abdominal surgery. Cellular and morphological changes follow a period of malnutrition. Enteral feeding is an important strategy for maintaining gut integrity and function. Controversies remain on the use of feeding jejunostomy after major abdominal surgery and its use had not gained widespread acceptance. The records of 262 consecutive patients who underwent esophagectomy for cancer were reviewed retrospectively to assess whether the placement of a needle catheter jejunostomy (NCJ) at the time of surgery is a safe and useful procedure. All the patients had a 9 Fr. NCJ place in a standardized fashion at the time of the esophagectomy. The technique of placement, the utilisation, and the complications of the NCJ were examined. The enteral nutrition was started in the first post‐operative day. Sixty‐three percent of our patients required enteral nutrition for 10 or more days. In 19%, this requirement was prolonged for more then 20 days, upto 68 days. The complications related to NCJ were four (1.5%). The use of the NCJ as described is safe, with an extremely low rate of complications. It may provide adequate nutritional support for a prolonged period of time at low costs. Its routine use in patients undergoing esophagectomy is recommended. J. Surg. Oncol. 2005;91:276–279. © 2005 Wiley‐Liss, Inc.
Laparoscopic cholecystectomy for treatment of unexpected early‐stage gallbladder cancer
Authors: Sun Chuan Dong , Zhang Bing Yuan , Wu Li Qun , Lee Woo Jung
Published: August 2005

Background and Objectives

Laparoscopic cholecystectomy (LC) may result in the incidental diagnosis of early stage (T1 and T2) gallbladder cancer. LC is useful for T1 patients, however, its role in T2 patients remains controversial. We sought to determine the effect of initial LC on patient outcome in early‐stage gallbladder cancer.

Methods

Twenty‐nine patients with T1 or T2 disease were reviewed retrospectively to assess preoperative diagnosis, intraoperative findings, and outcomes.

Results

Diagnoses included gallbladder stones (5), gallstones with polyps (5), and gallbladder polyps (19). Malignancy was suspected in 15 patients (14 polyp lesions and 1 gallbladder stone with wall thickening). After frozen sections, two T2 patients were immediately treated with radical operation owing to positive margins. Of 14 patients diagnosed by pathology, 4 T2 patients with positive margins underwent a second radical operation. Five‐year survival rate was 100% and 49.6 % (T1 and T2 patients). No mortality or recurrence was detected in T1 patients (mean follow‐up, 45.8 months; range, 6–98 months). Three T2 patients died, and one T2 patient relapsed after LC. No port site metastasis was detected.

Conclusions

LC for T1a and T1b gallbladder cancer needs no additional treatment, however, radical operation for T2 patients is recommended, regardless of the margin condition. J. Surg. Oncol. 2005;91:253–257. © 2005 Wiley‐Liss, Inc.
Disaster‐related posttraumatic stress symptoms and sustained attention: Evaluation of depressive symptomatology and sleep disturbances as mediators
Authors: Meewisse Marie‐Louise , Nijdam Mirjam J. , de Vries Giel‐Jan , Gersons Berthold P.R. , Kleber Rolf J. , van der Velden Peter G. , Roskam Albert‐Jan , Christiaanse Berdi , Drogendijk Annelieke N. , Olff Miranda
Published: August 2005

Research about attentional functioning following trauma has almost exclusively been performed in patient populations with combat‐related posttraumatic stress disorder (PTSD). In this study the relationship between sustained attention and PTSD symptoms was examined in a community sample of survivors of a major disaster using the Paced Auditory Serial Addition Task (PASAT) and the Self‐Rating Scale for PTSD (SRS‐PTSD) 2–3 years postdisaster. Analyses revealed low but significant partial correlations between PTSD symptoms and the least difficult subtests, ruling out the effects of age, education, depressive symptomatology, and sleep disturbances. These results demonstrate that PTSD symptoms link to attentional dysfunction 2–3 years postdisaster.
Disparities in mental health treatment following the World Trade Center Disaster: Implications for mental health care and health services research
Authors: Boscarino Joseph A. , Adams Richard E. , Stuber Jennifer , Galea Sandro
Published: August 2005

To assess disparities in mental health treatment in New York City (NYC) after the World Trade Center Disaster (WTCD) reported previously related to care access, we conducted analyses among a cross‐sectional survey of adults who had posttraumatic stress disorder (PTSD) or major depression (N = 473) one year after the event. The dependent variables examined were use of mental health services, in general, and use of mental health services related to the WTCD. Similar dependent variables were developed for medication usage. Although a number of bivariate results were statistically significant for postdisaster mental health visits, in a multivariate logistic regression model, only WTCD exposure remained significant. For service utilization related to the WTCD, the multivariate results indicated that African Americans were less likely to have had these visits compared to Whites, while those with a regular doctor, who had greater exposure to WTCD events, and those who had a perievent panic attack were more likely to have had such visits. In terms of medication use, multivariate results suggested that African Americans were less likely to use postdisaster medications, whereas persons 45 + years old and those with a regular doctor, were more likely to use them. For WTCD‐related medication use, multivariate models indicated that African Americans were less likely to use medications, relative to Whites, while those between 45 and 64 years old, those with a regular doctor, those exposed to more WTCD events, and those who had a perievent panic attack, were more likely to have taken medications related to the disaster. The primary reason respondents gave for not seeking treatment (55% of subsample) was that they did not believe that they had a problem (73%). Other reasons were that they wanted to solve the problem on their own (5%), had problems accessing services (6%), had financial problems (4%), or had a fear of treatment (4%). Despite the availability of free mental health services offered in a supportive and potentially less stigmatizing environment post disaster, there still appeared to be barriers to receiving postdisaster services among those presumably in need of care.
Crystallization, Melting and Morphology of Syndiotactic/Atactic Polystyrene Blends: Molecular Weight Effects of Atactic Polystyrene
Authors: Wang Chi , Wang Ming‐Ling , Fan Yong‐Da
Published: August 2005

Summary: Molecular weight (MW) effects of atactic polystyrene (aPS) on the morphologies and crystallization kinetics of syndiotactic polystyrene (sPS) blends have been investigated, and miscibility was confirmed for all the sPS/aPS blends. Addition of aPS(M) or aPS(L) leads to a significant increase in the entropy of mixing and gives rise to a pronounced decrease in the equilibrium melting temperature of the blends. On heating from the glassy state, the crystallization peak temperature of the sPS/aPS(H) blend increased with increasing aPS content due to a dilution effect, whereas those of sPS/aPS(M) and sPS/aPS(L) decreased mainly due to enhanced chain mobility. On cooling from the melt state, the crystallization peak temperature decreased with increasing aPS content regardless of the aPS MW. A higher activation energy is required for the sPS component transport from the miscible melt to the growth front in the sPS/aPS(L), suggesting that extra energy is required for the demixing process. Interspherulitic segregation of aPS diluents was evident in the sPS/aPS(L) blends, while interfibrillar segregation morphology was obtained in the sPS/aPS(H) as well as the sPS/aPS(U) blends.

SEM images of sPS/aPS blends 50/50(L) at 230 °C (C) and 70/30(L) at 250 °C (D).

magnified image

SEM images of sPS/aPS blends 50/50(L) at 230 °C (C) and 70/30(L) at 250 °C (D).
The effective action of D‐branes in Calabi‐Yau orientifold compactifications
Authors: Jockers H.
Published: August 2005

In this review article we study type IIB superstring compactifications in the presence of space‐time filling D‐branes while preserving 𝒩=1 supersymmetry in the effective four‐dimensional theory. This amount of unbroken supersymmetry and the requirement to fulfill the consistency conditions imposed by the space‐time filling D‐branes lead to Calabi‐Yau orientifold compactifications. For a generic Calabi‐Yau orientifold theory with space‐time filling D3‐ or D7‐branes we derive the low‐energy spectrum. In a second step we compute the effective 𝒩=1 supergravity action which describes in the low‐energy regime the massless open and closed string modes of the underlying type IIB Calabi‐Yau orientifold string theory. These 𝒩=1 supergravity theories are analyzed and in particular spontaneous supersymmetry breaking induced by non‐trivial background fluxes is studied. For D3‐brane scenarios we compute soft‐supersymmetry breaking terms resulting from bulk background fluxes whereas for D7‐brane systems we investigate the structure of D‐ and F‐terms originating from worldvolume D7‐brane background fluxes. Finally we relate the geometric structure of D7‐brane Calabi‐Yau orientifold compactifications to 𝒩=1 special geometry.
Effects of the stabilization of the molten globule state on the folding mechanism of α‐lactalbumin: A study of a chimera of bovine and human α‐lactalbumin
Authors: Mizuguchi Mineyuki , Matsuura Atsushi , Nabeshima Yuko , Masaki Kazuo , Watanabe Masahiro , Aizawa Tomoyasu , Demura Makoto , Nitta Katsutoshi , Mori Yoshihiro , Shinoda Hiroyuki , Kawano Keiichi
Published: August 2005

The N‐terminal half of the α‐domain (residues 1 to 34) is more important for the stability of the acid‐induced molten globule state of α‐lactalbumin than the C‐terminal half (residues 86 to 123). The refolding and unfolding kinetics of a chimera, in which the amino acid sequence of residues 1 to 34 was from human α‐lactalbumin and the remainder of the sequence from bovine α‐lactalbumin, were studied by stopped‐flow tryptophan fluorescence spectroscopy. The chimeric protein refolded and unfolded substantially faster than bovine α‐lactalbumin. The stability of the molten globule state formed by the chimera was greater than that of bovine α‐lactalbumin, and the hydrophobic surface area buried inside of the molecule in the molten globule state was increased by the substitution of residues 1 to 34. Peptide fragments corresponding to the A‐ and B‐helix of the chimera showed higher helix propensity than those of the bovine protein, indicating the contribution of local interactions to the high stability of the molten globule state of the chimera. Moreover, the substitution of residues 1–34 decreased the free energy level of the transition state and increased hydrophobic surface area buried inside of the molecule in the transition state. Our results indicate that local interactions as well as hydrophobic interactions formed in the molten globule state are important in guiding the subsequent structural formation of α‐lactalbumin. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Simplifying Monotonicity Conditions for Entanglement Measures
Authors: Horodecki Michał
Published: August 2005

We show that for a convex function the following, rather modest conditions, are equivalent to monotonicity under local operations and classical communication. The conditions are: (i) invariance under local unitaries, (ii) invariance under adding local ancilla in arbitrary state (iii) on mixtures of states possessing local orthogonal flags the function is equal to its average. The result holds for multipartite systems. It is intriguing that the obtained conditions are equalities. The only inequality is hidden in the condition of convexity.
Effect of Heat Transfer Law on the Ecological Optimization of a Generalized Irreversible Carnot Engine
Authors: Zhu Xiaoqin , Chen Lingen , Sun Fengrui , Wu Chih
Published: August 2005

The optimal ecological performance of a irreversible Carnot engine with the losses of heat-resistance, heat leak and internal irreversibility, in which the transfer between the working fluid and the heat reservoirs obeys a generalized heat transfer law Q ∝ ∆(Tn), is derived by taking an ecological optimization criterion as the objective, which consists of maximizing a function representing the best compromise between the power and entropy production rate of the heat engine. Some special examples are discusses. A numerical example is given to show the effects of heat transfer law, heat leakage and internal irreversibility on the optimal performance of the generalized irreversible heat engine. The results can provide some theoretical guidance for the designs of practical engine.
A brief statistical sketch of the child labour market in mid-nineteenth-century London
Authors: KIRBY PETER
Published: August 2005

The profusion of small trades and services that characterized the nineteenth-century London labour market makes it extremely difficult to arrive at any general understanding of the work of children and juveniles. This brief study employs published statistical materials and compares children's occupations in the metropolis with the national picture. It argues that London contained exceptionally low levels of children's employment compared with the rest of England and Wales. The preoccupation of metropolitan social observers with working children may have resulted from the fact that child employment in mid-nineteenth-century London was a marginal activity associated chiefly with the very poor.
Molecular therapeutic targets in rheumatoid arthritis
Authors: Sacre Sandra M. , Andreakos Evangelos , Taylor Peter , Feldmann Marc , Foxwell Brian M.
Published: August 2005

In an attempt to combat the pain and damage generated by rheumatoid arthritis (RA), new drugs are being developed to target molecular aspects of the disease process. Recently, a major development has been the use of biologicals (antibodies and soluble receptors) that neutralise the activity of tumour necrosis factor α (TNF-α) and interleukin 1 (IL-1), both of which are involved in disease progression. An increase in our understanding of cell and molecular biology has resulted in the identification and investigation of potential new targets, and also the refinement and improvement of current therapeutic modalities. This review describes therapies that are approved, in clinical trials or under pre-clinical investigation at the laboratory level, particularly focusing on cytokines, although other therapeutic targets of interest are mentioned.
Implications of decreased serum adiponectin for type IIb hyperlipidaemia and increased cholesterol levels of very-low-density lipoprotein in type II diabetic patients
Authors: Yoshida Hiroshi , Hirowatari Yuji , Kurosawa Hideo , Tada Norio
Published: August 2005

The present study was performed to investigate the relevance of cholesterol levels of plasma lipoproteins [HDL (high-density lipoprotein), LDL (low-density lipoprotein), IDL (immediate-density lipoprotein), VLDL (very-LDL) and chylomicrons] determined by a novel HPLC method, with adiponectin, which is decreased in Type II diabetes and assumed to be involved in dysregulated metabolism and atherogenesis. Type II diabetic patients who were not treated with insulin, statins and fibrates were enrolled. Study subjects included Type II diabetic patients with normolipidaemia (DM-NL; n=15), type 4 hyperlipidaemia (DM-T4HL; n=13), Type IIa hyperlipidaemia (DM-T2aHL; n=15) and Type IIb hyperlipidaemia (DM-T2bHL; n=13). Fasting blood samples were collected. The serum adiponectin level was lower in DM-T2bHL than in any of the other groups. Cholesterol levels of each lipoprotein fraction, serum triacylglycerol (triglyceride), remnant-like particle-cholesterol, fasting plasma glucose, HbA1c (glycated haemoglobin), age, gender difference and BMI (body mass index) were incorporated into a stepwise regression analysis as independent variables. VLDL-cholesterol correlated inversely with adiponectin independently of age, BMI, gender difference and glycaemic control. Although the mechanisms remain to be explored, serum adiponectin was reduced particularly in Type II diabetics with type IIb hyperlipidaemia and correlated inversely with VLDL-cholesterol. Measuring VLDL-cholesterol may be helpful for understanding the pathological features of diabetic dyslipidaemia.
Large amplitude quantum mechanics in polyatomic hydrides. I. A particles-on-a-sphere model for XHn
Authors: Deskevich Michael P. , Nesbitt David J.
Published: August 2005

A framework is presented for converged quantum mechanical calculations on large amplitude dynamics in polyatomic hydrides (XHn) based on a relatively simple, but computationally tractable, “particles-on-a-sphere” (POS) model for the intramolecular motion of the light atoms. The model assumes independent two-dimensional (2D) angular motion of H atoms imbedded on the surface of a sphere with an arbitrary interatomic angular potential. This assumption permits systematic evolution from “free rotor” to “tunneling” to “quasi-rigid” polyatomic molecule behavior for small, but finite, values of total angular momentum J. This work focuses on simple triatom (n=2) and tetratom (n=3) systems as a function of interatomic potential stiffness, with explicit consideration of H2O, NH3, and H3O+ as limiting test cases. The POS model also establishes the necessary mathematical groundwork for calculations on dynamically much more challenging XHn species with n>3 (e.g., models of CH5+) where such a reduced dimensionality approach offers prospects for being quantum mechanically tractable at low J values (i.e., J=0, 1, 2) characteristic of supersonic jet expansion conditions.
Generalized nuclear Fukui functions in the framework of spin-polarized density-functional theory
Authors: Chamorro E. , De Proft F. , Geerlings P.
Published: August 2005

An extension of Cohen’s nuclear Fukui function is presented in the spin-polarized framework of density-functional theory (SP-DFT). The resulting new nuclear Fukui function indices ΦNα and ΦSα are intended to be the natural descriptors for the responses of the nuclei to changes involving charge transfer at constant multiplicity and also the spin polarization at constant number of electrons. These generalized quantities allow us to gain new insights within a perturbative scheme based on DFT. Calculations of the electronic and nuclear SP-DFT quantities are presented within a Kohn-Sham framework of chemical reactivity for a sample of molecules, including H2O, H2CO, and some simple nitrenes (NX) and phosphinidenes (PX), with X=H, Li, F, Cl, OH, SH, NH2, and PH2. Results have been interpreted in terms of chemical bonding in the context of Berlin’s theorem, which provides a separation of the molecular space into binding and antibinding regions.
Influence of formation path on the CH2BrCl2+ dissociation dynamics
Authors: Le Guen K. , Ahmad M. , Céolin D. , Lablanquie P. , Miron C. , Penent F. , Morin P. , Simon M.
Published: August 2005

To get further insight into the CH2BrCl site-selective fragmentation previously observed upon inner-shell ionization, we have performed high-resolution Br 3d and Cl 2p Auger and spin-orbit resolved Br 3d Auger spectra, and studied the dissociation properties of the CH2BrCl2+ dication formed at threshold by means of threshold electron pair-ion coincidence measurements. The key point is that the origin of site-specific bond breaking is found in the Auger decay itself, as it preferentially populates selected dication states. Whereas the predominance of the CBr bond breaking is observed in both threshold and inner-shell studies, no signature of selective CCl rupture is reported for the dication formed at threshold.
Performance comparison of optically pumped type-II midinfrared lasers
Authors: Ongstad A. P. , Kaspi R. , Tilton M. L. , Chavez J. R. , Dente G. C.
Published: August 2005

We report a comparative study on the performance of three optically pumped, type-II quantum well lasers with differing quantum well (QW) confinement. One of the active regions emphasized hole confinement, another emphasized electron confinement, while the third incorporated both electron and hole confinements. In all cases the wells were inserted in a thick InxGa1−xAsySb1−y waveguide/absorber region. The lasing wavelengths at 84K were 2.26, 3.44, and 2.37μm, respectively. The maximum peak output powers and differential quantum efficiencies η at 84K were similar for the hole well and W lasers (≈13W,η≈0.55), but significantly reduced in the electron-well-only laser (2.3W,η=0.14). Waveguide loss measurements via the traditional quantum efficiency versus cavity length method and by a Hakki-Paoli method revealed that all three lasers had low waveguide loss that either increased slowly or not at all with increasing temperature. However, the laser’s internal efficiency, ηi, showed a linear decline with increasing temperature, with the ηi of the electron-well-only laser significantly less than the other two. The data suggest that for antimonide-based type-II designs, strong hole confinement is essential for improved performance. The data further suggest that it is hole leakage from the QW and/or hole dilution that is largely responsible for the degradation in laser performance.
Mo 2 C nanowires and nanoribbons on Si by two-step vapor-phase growth
Authors: Tsakalakos L. , Rahmane M. , Larsen M. , Gao Y. , Denault L. , Wilson P. , Balch J.
Published: August 2005

Transition-metal carbides in bulk form have historically been of technological interest primarily due to their excellent mechanical and refractory properties. As electronic materials these ceramic compounds are also particularly intriguing in that their electrical resistivity is relatively low compared to other ceramics and shows metallic temperature-dependent behavior. Some compositions also have superconducting transitions temperatures above 10°K. However, the synthesis of such materials in the form of one-dimensional nanostructures, which may be of interest for various nanoelectronic applications, is relatively difficult due to their refractory nature (Tmelt⩾2000°C). Here we report the synthesis of well-defined Mo2C nanowires and ribbons using a two-step approach in which we catalytically grow metal oxide nanostructures followed by in situ carburization. The growth mechanisms, microstructure, and initial electrical property measurements are discussed.
Near-edge x-ray absorption fine-structure fingerprints of bulk-amorphous and nanostructured Pd-based alloys
Authors: Kapaklis V. , Poulopoulos P. , Wilhelm F. , Jaouen N. , Rogalev A. , Politis C.
Published: August 2005

Bulk amorphous PdCuNiP alloys have been prepared from the liquid state by means of solidification under an argon atmosphere. The addition of a small amount of Fe (∼5at.%) results in the formation of nanocrystalline inclusions inside the residual amorphous matrix. Element-specific near-edge x-ray absorption fine-structure spectroscopy provides information on the electronic structure and symmetry properties of the samples. In combination with conventional θ–2θ x-ray diffraction mesurements, it allows for the investigation of the modifications in structure after the addition of Fe, as well as for the determination of the most probable crystalline phases. The results are discussed in terms of thermodynamics.
Orientation discrimination of single-stranded DNA inside the α-hemolysin membrane channel
Authors: Mathé Jérôme , Aksimentiev Aleksei , Nelson David R. , Schulten Klaus , Meller Amit
Published: August 2005

We characterize the voltage-driven motion and the free motion of single-stranded DNA (ssDNA) molecules captured inside the ≈1.5-nm α-hemolysin pore, and show that the DNA–channel interactions depend strongly on the orientation of the ssDNA molecules with respect to the pore. Remarkably, the voltage-free diffusion of the 3′-threaded DNA (in the trans to cis direction) is two times slower than the corresponding 5′-threaded DNA having the same poly(dA) sequence. Moreover, the ion currents flowing through the blocked pore with either a 3′-threaded DNA or 5′ DNA differ by ≈30%. All-atom molecular dynamics simulations of our system reveal a microscopic mechanism for the asymmetric behavior. In a confining pore, the ssDNA straightens and its bases tilt toward the 5′ end, assuming an asymmetric conformation. As a result, the bases of a 5′-threaded DNA experience larger effective friction and forced reorientation that favors co-passing of ions. Our results imply that the translocation process through a narrow pore is more complicated than previously believed and involves base tilting and stretching of ssDNA molecules inside the confining pore.
The double vocal signature of crested penguins: is the identity coding system of rockhopper penguins Eudyptes chrysocome due to phylogeny or ecology?
Authors: Searby Amanda , Jouventin Pierre
Published: August 2005

Parent‐offspring recognition systems are used in bird colonies to avoid misdirected parental care. In penguins, where the risk of confusion is particularly high, recognition is achieved by acoustic signals that constitute highly efficient vocal signatures. Comparisons between species from the Pygoscelis and Aptenodytes genera have revealed interspecific differences on the encoding of information within the signatures which correlate with the presence/absence of nests in the colonies. However a recent study of individual recognition in macaroni penguins Eudyptes chrysolophus revealed diversity within nest‐building species. This paper investigates whether the original and intermediate signature system found in macaroni penguins is shared by another species of Eudyptes, the rockhopper penguin E. chrysocome. Vocal signatures of rockhopper penguins were analysed and compared to macaroni penguins’. We used a methodology derived from the theory of information to determine which parameters of the call were likely to encode individual identity. Playbacks of modified calls in the field complemented the analyses, and parent‐chick reunions were compared between the two species. Our results reveal a similar double signature system within the Eudyptes genus, which integrates information simultaneously from the temporal and spectral domains. This double encoding is made through the tempo given by the successive syllables of the call and the harmonic content of the call. While it confirms the hypothesis that signatures are simpler in nest‐building species, this result reveals differences in the efficacies of signatures within this category. This suggests that other parameters such as the mean distance recognition should be considered to account for the differences in the encoding of the vocal signatures and in their resulting efficacies.
Establishment and Characterization of Mouse‐Human Chimeric Monoclonal Antibody to erbB‐2 Product
Authors: Ishida Tadao , Tsujisaki Masayuki , Hinoda Yuji , Imai Kohzoh , Yachi Akira
Published: August 2005

A mouse‐human chimeric antibody for erbB‐2 product was established by a new procedure using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The E401 hybridoma secreted anti‐erbB‐2 product monoclonal antibody (MoAb) (IgG1, k). The gene of the mouse variable regions of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the E401 hybridoma RNA. The variable region of heavy chain was joined with the expression vector, which contains human γ1 constant gene. The expression vector was transfected into heavy chain loss mutant cells E401‐12, which produced only murine immunoglobulin light chains. A chimeric monoclonal antibody CH401 retained full binding reactivity to erbB‐2 product, compared with murine E401 parental antibody. Furthermore, the chimeric MoAb CH401 was much more efficient in supporting antibody dependent cell‐mediated cytotoxicity activity against erbB‐2‐bearing human adenocarcinoma cells than murine MoAb E401. These suggest that a chimeric monoclonal antibody CH401 may be a potent reagent for therapy of human adenocarcinomas.
Different Modes of Cell‐killing Action between DNA Topoisomerase I and II Inhibitors Revealed by Kinetic Analysis
Authors: Inaba Makoto , Mitsuhashi Junko , Kawada Shouzou , Nakano Hirofumi
Published: August 2005

We compared the modes of cell‐killing by DNA topoisomerase I and II inhibitors. The effects of camptothecin (CPT), KT‐6528 and UCE6 upon colony formation by inhibiting DNA topoisomerase I, and of etoposide (VF‐16), teniposide, amsacrine and UCT4‐A as inhibitors of DNA topoisomerase II were analyzed based upon a kinetic method that distinguishes between cell cycle phase‐specific and ‐nonspecific agents. Human colorectal cancer WiDr cells were exposed to several concentrations of each agent for various periods and 90%‐inhibitory concentrations (IC90) at each time were determined by means of a clonogenic assay. When exposure times and corresponding IC90s were plotted on a log‐log scale, all inhibitors of DNA topoisomerase II gave curves including a linear portion with a slope of −1, which is characteristic of cell cycle phase‐nonspecific agents. In contrast, the curves for all inhibitors of DNA topoisomerase I had a much steeper slope than −1, which is typical of cell cycle phase‐specific agents. In agreement with this finding, the cells were remarkably accumulated in the G2‐M phase when exposed to VP‐16, but in late S‐phase when exposed to CPT as determined by a flow cytometric assay. These results indicated that the two classes of agents kill cells in a quite different manner although they are inhibitors of similar enzymes.
Reconstitution of Anti‐tumor Effects of Lentinan in Nude Mice: Roles of Delayed‐type Hypersensitivity Reaction Triggered by CD4‐positive T Cell Clone in the Infiltration of Effector Cells into Tumor
Authors: Suzuki Manabu , Iwashiro Michihiro , Takatsuki Fumihiko , Kuribayashi Kagemasa , Hamuro Junji
Published: August 2005

Lentinan, an antitumor polysaccharide used clinically in Japan, requires the intact T cell compartment to manifest its antitumor effects. The aim of the current study was to clarify the mechanisms playing crucial roles in the T cell requirement in the expression of antitumor effects of lentinan. Lentinan treatment of BDF1 mice transplanted intradermally with FBL‐3 induced complete tumor regression and a marked increase in survival time. The antitumor action of lentinan was abolished in mice treated simultaneously with antibodies to CD4 and CD8 antigens, whereas antibody to CD4, CD8 or NK1.1 alone was ineffective. The natural killer, cytotoxic T lymphocyte, and helper T cell activities were already augmented in this FBL‐3/BDF1 system and thus further augmentation of these activities by lentinan was not observed. These activities did not correlate with the antitumor activity of lentinan, as was confirmed in lymphocyte subset depletion experiments. On the contrary, the delayed‐type hypersensitivity (DTH) response against tumor‐associated antigens was triggered by lentinan and was abrogated only in mice treated simultaneously with antibodies to CD4 and CD8 antigens. Furthermore, a non‐cytolytic tumor‐associated antigen‐specific CD4+ T cell clone able to induce the DTH response in concert with lentinan reconstituted the antitumor effects in B6 nude mice when administered with lentinan. These results suggest that, in addition to the augmentation of immune effector cell activity against tumors, infiltration of these cells into the tumor burden initiated by the DTH responses at tumor sites may be involved in eradication of tumors by lentinan.
Absence of p53 Mutations in Rat Colon Tumors Induced by 2‐Amino‐6‐methyldipyrido[1,2‐a:3′, 2′‐d]imidazole, 2‐Amino‐3‐methylimidazo[4,5‐f]quinoline, or 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine
Authors: Makino Hiroshi , Ushijima Toshikazu , Kakiuchi Hideki , Onda Masahiko , Ito Nobuyuki , Sugimura Takashi , Nagao Minako
Published: August 2005

Colon tumors were induced in F344 rats by three heterocyclic amines (HCAs), 2‐amino‐6‐methyl‐dipyrido[1,2‐a:3′, 2′‐d]imidazole (Glu‐P‐1), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) or 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), and examined for p53 mutations. Seven carcinomas induced by Glu‐P‐1, and nine carcinomas and two adenomas induced by IQ were examined by cDNA‐polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis from codon 103 to 391 of p53, which encompasses the conserved regions II to IV. Nine carcinomas induced by PhIP were examined by genomic PCR‐SSCP analysis of exons 5 to 7 (from codon 124 to 304), which encompasses the 3’half of the conserved region II and all the conserved regions III‐V. No band shifts were found in any of these tumors under at least two conditions of SSCP analysis. Our previous study had shown a Ki‐ras mutation in only one Glu‐P‐1‐induced adenocarcinoma among the same 27 colon tumors, and no other mutation of ras family genes had been found. HCA‐induced rat colon tumors appear to represent a group of human colon tumors in which neither Ki‐ras nor p53 is involved.
Loss of Heterozygosity at the bcl‐2 Gene Locus and Expression of bcl‐2 in Human Gastric and Colorectal Carcinomas
Authors: Ayhan Ayse , Yasui Wataru , Yokozaki Hiroshi , Seto Masao , Ueda Ryuzo , Tahara Eiichi
Published: August 2005

The loss of heterozygosity (LOH) at the bcl‐2 gene locus and the expression of the bcl‐2 gene were examined in gastric and colorectal carcinoma cell lines and carcinoma tissues. LOH at the bcl‐2 locus was detected in 24% (4/17) of gastric and 60% (6/10) of colonic carcinomas, all of which were well differentiated adenocarcinomas, whereas LOH was not seen in poorly differentiated ones. On the other hand, 24% (5/21) of poorly differentiated stomach cancers overexpressed bcl‐2 gene, whereas no overexpression was detected in well differentiated stomach cancer. Three gastric and three colorectal carcinoma cell lines, all of which were derived from poorly differentiated adenocarcinomas, expressed considerable levels of bcl‐2 mRNA and protein. These results suggest that LOH at the bcl‐2 locus is frequently associated with well differentiated adenocarcinomas of the stomach and colon, and bcl‐2 overexpression has implications for the development of poorly differentiated adenocarcinomas of the gastrointestinal tract.
Chemical Modification of Natural Human Tumor Necrosis Factor‐α with Polyethylene Glycol Increases Its Anti‐tumor Potency
Authors: Tsutsumi Yasuo , Kihira Tetsunari , Yamamoto Susumu , Kubo Kazuyoshi , Nakagawa Shinsaku , Miyake Masaharu , Horisawa Yoshifumi , Kanamori Toshinori , Ikegami Hakuo , Mayumi Tadanori
Published: August 2005

Natural human tumor necrosis factor‐α (TNF‐α) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG‐modified TNF‐a depended on the reaction time as well as the initial molar ratio of PEG to TNF‐α. The specific activity of modified TNF‐α was gradually reduced with increase in the degree of PEG‐modification, but the plasma half‐life of TNF‐α was increased by up to 40‐fold. Modified TNF‐α showed approximately 100 times greater anti‐tumor potency than unmodified TNF‐α. Covalent attachment of PEG to TNF‐α thus increased the bioavailability of TNF‐α, and may facilitate its potential therapeutic use.
Abundant but Inactive‐state gpl40prototrk Is Expressed in Neuroblastomas of Patients with Good Prognosis
Authors: Iwata Hiroyuki , Ito Takahiro , Mutoh Tatsuro , Ishiguro Yukio , Xiao Hengyi , Hamaguchi Michinari
Published: August 2005

Steady‐state levels of gp140proto‐trk in cell lines and tumor tissues of neurohlastoma were examined by immunoblotting with anti‐gpl40proto‐trk The level of gpl40proto‐trk varied but showed good correlations with the stage of the tumor and the age of the patients at the time of diagnosis. Moreover, patients with higher expression of gpl40proto‐trk clearly had a far better survival rate than those with lower expression, suggesting that suppression of gp140proto‐trkstrongly correlates with the malignant conversion of the tumor. However, we found that neither autophosphorylation of gpl40proto‐trknor tyrosine phosphoryla‐tion of cellular proteins was elevated in tumors of the higher expression group. These results suggest that gpl40proto‐trk does not actively participate in the process of transformation or the suppression of malignant conversion. Rather, the higher level of gpl40proto‐trkmay reflect the greater level of differentiation of tumor cells.
Cooperative Roles of Hepatocyte Growth Factor and Plasminogen Activator in Tubular Morphogenesis by Human Microvascular Endothelial Cells
Authors: Morimoto Akio , Tada Katsuhiro , Nakayama Yoshifumi , Kohno Kimitoshi , Naito Seiji , Ono Mayumi , Kuwano Michihiko
Published: August 2005

Epidermal growth factor (EGF) or transforming growth factor‐α (TGF‐α) stimulated cell migration, chemotaxis, and the expression of tissue‐type plasminogen activator (t‐PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t‐PA and tube‐like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase‐type plasminogen activator (u‐PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high‐ and low‐affinity receptors for HGF. In BAE cells, u‐PA activity and tube‐like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t‐PA activity and tube‐like structures were induced in the presence of TGF‐a alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t‐PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co‐cultured with a renal cancer cell line, KPK13, tube‐like structures were induced in the presence of HGF: KPK13 cells expressed large amounts of t‐PA mRNA. Our present study suggested that HGF in concert with active t‐PA could be angiogenic in HOME cells.
Phase I and Pharmacokinetic Study of Paclitaxel by 24‐Hour Intravenous Infusion
Authors: Tamura Tomohide , Sasaki Yasutsuna , Eguchi Kenji , Shinkai Tetsu , Ohe Yuichiro , Nishio Makoto , Kunikane Hiroshi , Arioka Hitoshi , Karato Atsuya , Omatsu Hironobu , Nakashima Hajime , Saijo Nagahiro
Published: August 2005

Paclitaxel, a new antitubular agent, appears to be one of the most promising single agents for the chemotherapy of various solid tumors. The primary objectives of this phase I study of paclitaxel using 24‐h continuous intravenous infusions were to determine the maximum tolerated dose of paclitaxel administered by this schedule to Japanese patients with solid tumors and to evaluate the pharmaco‐kiiietics of paclitaxel. Eighteen patients received one of five doses of paclitaxel, 49.5, 75, 105, 135 or 180 mg/m2. Prcmedication with diphenhydramine, dexamethasone, and ranitidine was used to prevent acute hypersensitivity reactions. Pharmacokinetic data were obtained from all 18 patients. Dose‐limiting toxicities observed at 180 mg/m2 consisted of grade 4 granulocytopenia associated with grade 3 infection. No severe HSRs or cardiac toxicity were detected. Reversible toxicities observed included liver dysfunction, alopecia, peripheral neuropathy and myalgias. Pharmacokinetic studies performed using high‐performance liquid chromatography demonstrated that plasma concentrations of paclitaxel increased during the 24‐h infusion and declined immediately upon cessation of the infusion with a half life of 13.1‐24.6 h (75‐180 mg/m2). Less than 10% of paclitaxel was excreted in the urine within 72 h. The peak plasma concentrations and the areas under the concentration‐versus‐time curves increased linearly with the dose administered. Antitumor activity was observed in one patient with pulmonary metastasis from pharyngeal cancer. Based on these studies a phase II trial dose of 135 mg/m2 administered over 24 h was chosen.
Isolation of Genes Differentially Expressed between the Yoshida Sarcoma and Long‐survival Yoshida Sarcoma Variants: Origin of Yoshida Sarcoma Revisited
Authors: Tsuchiya Haruo , Tsuchiya Yuri , Kobayashi Toshiyuki , Kikuchi Yasushi , Hino Okio
Published: August 2005

The Yoshida sarcoma (YS) is characterized by growth as “free cells” in ascites. Long‐survival Yoshida sarcoma (LY) variants, which develop after transplantation of YS into immunologically conditioned Donryu rats, in contrast, form “islands” in ascites. A representational difference analysis (RDA) approach was adopted to isolate genes differentially expressed between YS and LY variants to elucidate the molecular mechanism of their development. Fifteen clones presenting differences in expression were characterized. Nine genes (those encoding for the high‐affinity IgE receptor γ chain, pJG116 repetitive sequence, non neuronal enolase, proteasome subunit RC1, cytotoxic T lymphocyte‐associated gene transcript CTLA‐1, interleukin‐2 receptor γ chain, and three unknown sequences) expressed mRNA in YS, but showed lower or no expression of mRNA in LYs. The mRNAs of the other six genes (those encoding for cytokeratin 8, cytokeratinlS (Endo B), TIMP2 and three unknown sequences) were not found in YS, but were present in LYs. Interestingly, CTLA‐1 is a non‐epithelial (hematopoietic) cell‐specific gene in terms of transcription, while cytokeratin 8 and cytokeratin 18 are both epithelium‐specific genes. Immunohistochemically, YS expressed T‐cell specific antigens CD2 and CDS, and T cell receptor β and γ chain genes were rearranged in YS, but not in LYs. Moreover, using restriction fragment length polymorphism probes, we found that LYs exhibited different cell lineage from YS. Thus, our present findings, unexpectedly, raise fundamental questions concerning the cellular origins of YS and LY variants rather than pointing to any specific mechanism to explain the LY phenomenon.