bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurokinin B‐producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat
Authors: Zhou Ligang , Furuta Takahiro , Kaneko Takeshi
Published: November 2004

Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB‐producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB‐immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB‐immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB‐immunoreactive cell clusters into the LSS‐associated and non‐LSS‐associated ones. We next investigated the projection targets of the PPTB‐producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro‐Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB‐immunoreactive neurons were retrogradely labeled in the LSS‐associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB‐immunoreactivity frequently in non‐LSS‐associated cell clusters. Furthermore, these PPTB‐immunoreactive projections were confirmed by the double‐fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB‐producing dorsal striatal neurons, the present results indicate that PPTB‐producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. J. Comp. Neurol. 480:143–161, 2004. © 2004 Wiley‐Liss, Inc.
An experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). I: Olfactory bulb and ventral area
Authors: Folgueira Mónica , Anadón Ramón , Yáñez Julián
Published: November 2004

The fluorescent carbocyanine dye 1,1′‐dioctadecyl 3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to comprehensively analyze the connections of the olfactory bulbs and the different regions of the ventral (V) area of the telencephalic lobes (subpallium) of the rainbow trout. With this goal, DiI was applied to the different telencephalic nuclei and zones, as well as to the olfactory nerve, the olfactory bulb, the retina, and to several structures in the diencephalon and brainstem of juvenile trout. The olfactory bulbs maintain reciprocal connections with several regions of the telencephalon [ventral nucleus of V (Vv), supracommissural nucleus (Vs), posterior zone of D (Dp), preoptic nucleus], and also project to the diencephalon (posterior tuberal nucleus, posterior hypothalamic lobe). Vv receives afferents from Vs, the dorsal nucleus of V (Vd), the preoptic nucleus, and from several nuclei in the diencephalon and brainstem (suprachiasmatic nucleus, anterior and lateral tuberal nuclei, preglomerular complex, tertiary gustatory nucleus, posterior tubercle, inferior hypothalamic lobes, thalamus, torus semicircularis, secondary gustatory nucleus, locus coeruleus, superior raphe nucleus, central gray, and reticular formation), and projects to dorsal (pallial) regions and most of the nuclei afferent to Vv. The dorsal nucleus of V (Vd) and Vs mainly project to the dorsal area. In an accompanying article (Folgueira et al., 2004), we present the results of application of DiI to dorsal (pallial) telencephalic regions, as well as of several experiments of tracer application to extratelencephalic regions. The results presented here, together with those of the accompanying article, reveal a complex connectional pattern of the rainbow trout ventral telencephalon, most of these connections having not been described previously in salmonids. J. Comp. Neurol. 480:180–203, 2004. © 2004 Wiley‐Liss, Inc.
Afferent projections to nucleus reuniens of the thalamus
Authors: McKenna James Timothy , Vertes Robert P.
Published: November 2004

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and the major source of thalamic afferents to the hippocampus and parahippocampal structures. Nucleus reuniens has recently been shown to exert powerful excitatory actions on CA1 of the hippocampus. Few reports on any species have examined afferent projections to nucleus reuniens. By using the retrograde anatomical tracer Fluorogold, we examined patterns of afferent projections to RE in the rat. We showed that RE receives a diverse and widely distributed set of afferents projections. The main sources of input to nucleus reuniens were from the orbitomedial, insular, ectorhinal, perirhinal, and retrosplenial cortices; CA1/subiculum of hippocampus; claustrum, tania tecta, lateral septum, substantia innominata, and medial and lateral preoptic nuclei of the basal forebrain; medial nucleus of amygdala; paraventricular and lateral geniculate nuclei of the thalamus; zona incerta; anterior, ventromedial, lateral, posterior, supramammillary, and dorsal premammillary nuclei of the hypothalamus; and ventral tegmental area, periaqueductal gray, medial and posterior pretectal nuclei, superior colliculus, precommissural/commissural nuclei, nucleus of the posterior commissure, parabrachial nucleus, laterodorsal and pedunculopontine tegmental nuclei, nucleus incertus, and dorsal and median raphe nuclei of the brainstem. The present findings of widespread projections to RE, mainly from limbic/limbic‐associated structures, suggest that nucleus reuniens represents a critical relay in the transfer of limbic information (emotional/cognitive) from RE to its major targets, namely, to the hippocampus and orbitomedial prefrontal cortex. RE appears to be a major link in the two‐way exchange of information between the hippocampus and the medial prefrontal cortex. J. Comp. Neurol. 480:115–142, 2004. © 2004 Wiley‐Liss, Inc.
Dorsal root ganglion neurons up‐regulate the expression of laminin‐associated integrins after peripheral but not central axotomy
Authors: Wallquist Wilhelm , Zelano Johan , Plantman Stefan , Kaufman Stephen J. , Cullheim Staffan , Hammarberg Henrik
Published: November 2004

The favorable prognosis of regeneration in the peripheral nervous system after axonal lesions is generally regarded as dependent on the Schwann cell basal lamina. Laminins, a heterotrimeric group of basal lamina molecules, have been suggested to be among the factors playing this supportive role. For neurons to utilize laminin as a substrate for growth, an expression of laminin binding receptors, integrins, is necessary. In this study, we have examined the expression of laminin binding integrin subunits in dorsal root ganglion (DRG) neurons after transection to either their peripherally projecting axons, as in the sciatic nerve, followed by regeneration, or the centrally projecting axons in dorsal roots, followed by no or weak regenerative activity. In uninjured DRG, immunohistochemical staining revealed a few neurons expressing integrin subunit α6, whereas integrin subunits α7 and foremost β1 were expressed in a majority of neurons. After an injury to the sciatic nerve, mRNAs encoding all three integrins were up‐regulated in DRG neurons. By anterograde tracing, immunoreactivity for all studied integrins was also found in association with growing axons after a sciatic nerve crush lesion in vivo. In contrast, mRNA levels remained constant in DRG neurons after a dorsal root injury. Together with previous findings, this suggests that integrin subunits α6, α7, and β1 have an important role in the regenerative response following nerve injury and that the lack of regenerative capacity following dorsal root injury could in part be explained by the absence of response in integrin regulation. J. Comp. Neurol. 480:162–169, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of a Simple Solid Oxide Fuel Cell System with Gas Dynamic in Afterburner and Connecting Pipes
Authors: Chan S. H. , Ho H. K. , Ding O. L.
Published: November 2004

A simple solid oxide fuel cell plant is analysed based on the first law of thermodynamics approach. This system consists of a solid oxide fuel cell stack, a steam reformer, a mixer, a vaporiser, an afterburner, and two pre‐heaters. To simplify the study, the enthalpy at each node of the system is normalized with the lower heating value of the inlet fuel. A gas dynamic model for calculating the flow in the pipes connecting the system components is considered and can be used to estimate the flow velocity and friction‐induced pressure drop in the piping. Though the effect of a friction‐induced pressure drop can be significant in a sizeable integrated solid oxide fuel cell‐gas turbine power plant, it does not significantly affect the plant efficiency in this study, due to rather short piping used in this simple power system. A steady flow energy equation and the Rayleigh line flow assumption are applied to the afterburner to calculate the exit flow temperature, velocity and pressure.
Studies with condensed amino‐thiophenes: Further investigation of reactivity of amino‐thieno‐coumarines and amino‐thieno‐benzo[h]coumarines toward electron‐poor olefins and acetylenes
Authors: Abdelkhalik Mervat M. , Negm Abdalla M. , Elkhouly Ayatt I. , Elnagdi Mohammed H.
Published: November 2004

The reaction of 3‐amino‐5‐oxa‐2‐thia‐cyclopenta[a]naphthalene‐4‐one 2b with substituted acetylenes afforded C‐1 alkylation products. On the other hand, reaction of 17‐amino‐15‐methyl‐11‐oxa‐16‐thiacyclopenta[a]phenanthrene‐12‐one 5 with substituted acetylenes and electron‐poor olefins afforded the condensed thienopyridine derivatives 7 and 11a–c. The reaction of 5 with acrylonitrile and with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione afforded compounds 13 and 21 with loss of H2S via the expected [4 + 2] cycloaddition sequence. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:502–507, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20047
The reaction of triphenylarsine oxide with ethyl iodo‐acetate leading to triphenyl (carboethoxy)methylarsonium triiodide
Authors: Abalonin Boris E. , Nizamov Il'yas S. , Krivolapov Dmitry B. , Nizamov Il'nar D. , Khaibullin Ravil N. , Al'metkina Lyubov A. , Batyeva Elvira S. , Litvinov Igor A.
Published: November 2004

New data are presented for some processes accompaning “retro‐Arbuzov” reaction of tertiary arsine oxides with halogen‐containing reagents. Triphenyl (carboethoxy)methylarsonium triiodide 10a was obtained in the reaction of triphenylarsine oxide 1a with excess of ethyl iodoacetate 2a. The structure of 10a was established by X‐ray single crystal diffraction. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:482–485, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20050
Synthesis, spectral, and antimicrobial studies of 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones
Authors: Pathak Vijai N. , Gupta Ragini , Garg Meenu
Published: November 2004

Ketene generated from acetyl chloride or chloroacetyl chloride adds on indolyl Schiff's base double bond to afford 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones in THF. The reaction proceeds stereospecifically via concerted trans [2+2] cycloaddition. The synthesized compounds have been characterized by elemental analyses and spectral data (IR, PMR, and mass). All synthesized compounds have been evaluated for antibacterial and antifungal activities, and 4g to 4l have shown promising results. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:494–501, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20052
Synthesis of β‐monosubstituted α,β‐unsaturated amides with Z‐selectivity using diphenylphosphonoacetamides
Authors: Kojima Satoshi , Hidaka Tsugihiko , Ohba Yuko
Published: November 2004

The utility of diphenylphosphonoacetamides [(PhO)2P(O)CH2CONRR′] as Horner–Wadsworth–Emmons reagents was examined with five different patterns of substitution upon the amide nitrogen atom (2a: R, R′ = CH2Ph; 2b: R = CH2Ph, R′ = H; 2c: R = Me, R′ = OMe; 2d: R, R′ = Ph; 2e: R, R′ = (CH2)4). The reaction of 2a was found to be Z‐selective for aromatic aldehydes with selectivities up to 95:5. Reagent 2b led to reasonable selectivity for both benzaldehyde (85:15) and 3‐phenylpropionaldehyde (87:13), while 2c was somewhat effective for only the latter alkyl aldehyde (83:17). Compounds 2d and 2e exhibited slightly lower selectivities compared with 2a. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:515–523, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20054
Catechol–bisphosphonate conjugates: New types of chelators for metal intoxication therapy
Authors: Ding Huasheng , Xu Guangyu , Wang Junbo , Zhang Yunlong , Wu Xihan , Xie Yuyuan
Published: November 2004

Three new types of bisphosphonates conjugated with catechol were synthesized to explore their possibilities for the treatment of metal intoxication. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:549–555, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20056
Synthesis and characterization of trialkyltin esters of pyridinecarboxylic acids and crystal structure of [nBu3SnO2CC5H4N‐2]∞
Authors: Yin Han Dong , Wang Qi Bao , Xing Qiu Ju
Published: November 2004

Reactions of trialkyltin oxides with 2‐, 3‐, and 4‐pyridinecarboxylic acids in 1:1 stoichiometry yield 10 corressponding trialkyltin esters R3SnO2CC5H4N. All compounds are characterized by elemental analysis, IR, 1H, 113C, and 119Sn NMR. The crystal structure of tributyltin ester of 2‐pyridinecarboxylic acid is determined by single crystal X‐ray diffraction. In this compound, the tin atom is rendered five‐coordinate in a trigonal bipyramidal structure by coordinating with 2‐pyridinecarboxylate group. The resulting structure is a linear polymer containing SnO bonds (0.2278(5) and 0.2308(6) nm). © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:524–529, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20057
Synthesis and antitumor activity of novel 1‐(2′‐alkyl(or phenyl)thioethoxy)methyl‐5‐fluorouracils and their oxidation products
Authors: Liu Xue‐Jun , Chen Ru‐Yu , Bai Dong‐Lu
Published: November 2004

A series of novel 1‐(2′‐alkyl(or phenyl)thioethoxy)methyl‐5‐fluorouracils (6) were synthesized in three steps from 5‐fluorouracil. They were oxidized into sulfoxide (7) and sulfone (8) derivatives by NaIO4 and H2O2 30%/DEAD (diethyl azodicarboxylate), respectively, in high yields. In order to obtain structural information, sulfoxide 7g was characterized by X‐ray diffraction analysis. The preliminary bioassay indicated that the compounds 6a and 7g exhibit potential antitumor activity. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:543–548, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20059
TIMP1 and SERPIN‐A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma
Authors: Hawthorn Lesleyann , Stein Leighton , Varma Ram , Wiseman Samuel , Loree Thom , Tan DongFeng
Published: November 2004

Background.

No molecular pathways or specific genes are consistently associated with sporadic cases of papillary thyroid carcinoma (PTC), despite that it is the most common thyroid malignancy. Nodular goiter is an enlargement of the thyroid that is a compensatory response to a perturbation in normal thyroid homeostasis. It has been disputed in the literature that patients presenting with goiter have a higher incidence of PTC. The identification of molecular events that are common to both goiter and PTC could explain the overlap of these two disorders.

Methods.

We used high‐density oligonuleotide arrays to perform molecular profiling of PTC and nodular goiter with paired normal samples.

Results.

Specifically, increased expression of SERPIN‐A (proteinase inhibitor‐alpha antitrypsin) and TIMP 1 (tissue inhibitor of metalloproteinase 1) identified these as candidate molecular biomarkers for PTC. Decreases in the CRABP1 (cellular retinoic acid binding protein 1) and TFF3 (trefoil factor 3) expression levels identified these as candidate molecular biomarkers as well. The same analysis was performed to identify genes showing specific alterations in goiter tissues.

Conclusions.

This is the first report to our knowledge that compares the gene expression profiles of PTC and goiter. Our results suggest that PTC and goiter share very limited overlap in transcript expression. © 2004 Wiley Periodicals, Inc. Head Neck 26: 1069–1083, 2004
Use of modified Northwick Park Neck Pain Questionnaire in patients with postirradiation neck disability: Validation study
Authors: Yeung Polina L. C. , Chiu Thomas T. W. , Leung Arran S. L.
Published: November 2004

Background.

No available measure exists for postirradiation neck disability. Adoption of the Chinese Northwick Park Neck Pain Questionnaire (NPQ) for patients with postirradiation neck disability was examined in this study.

Methods.

Eight physiotherapists and five patients were invited to test the validity of the content. Forty‐three patients with neck disability were recruited to evaluate test–retest reliability and internal consistency. The level of neck discomfort, range of neck motion and maximal isometric neck muscle strength, and SF‐36 health score were measured for construct validity testing.

Results.

The questionnaire had good content validity, a high degree of test–retest reliability, internal consistency (intraclass correlation coefficient [ICC], 0.94; Cronbach's alpha, 0.88), and good construct validity. NPQ correlated significantly with most of the subscores of SF‐36 (rs, −0.43 to − 0.71) and numeric rating scale (rs = 0.69).

Conclusion.

The modified Chinese NPQ was found to be reliable and valid for the evaluation of postirradiation neck disability. © 2004 Wiley Periodicals, Inc. Head Neck 26: 1031–1037, 2004
Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck
Authors: Prasad Manju L. , Jungbluth Achim A. , Patel Snehal G. , Iversen Kristin , Hoshaw‐Woodard Stacy , Busam Klaus J.
Published: November 2004

Background.

Cancer testis antigens (CTAs) are T‐cell–defined tumor‐associated antigens encoded by the genes and gene families such as MAGE, NY‐ESO‐1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer. Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known.

Methods.

We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 57B, CT7‐33, and ES121 to the following CTAs: MAGE‐A4, CT7 (MAGE‐C1), and NY‐ESO‐1, respectively.

Results.

CT7, MAGE‐A4, and NY‐ESO‐1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE‐A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease‐specific survival.

Conclusions.

CT7, MAGEA4, and NY‐ESO‐1 are frequently expressed in HNMM and may be potential targets for CTA‐based immunotherapy. The expression does not seem to have prognostic significance. © 2004 Wiley Periodicals, Inc. Head Neck 26: 1053–1057, 2004
Regulation of gene expression in melanoma: New approaches for treatment
Authors: Leslie Michael C. , Bar‐Eli Menashe
Published: November 2004

The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase (VGP, metastatic phenotype) are not yet well defined. We have demonstrated that the progression of human melanoma is associated with loss of expression of the transcription factor AP‐2. In metastatic melanoma cells, this loss resulted in overexpression of MCAM/MUC18, MMP‐2, the thrombin receptor (PAR‐1), and lack of c‐KIT expression. The transition from RGP to VGP is also associated with overexpression of the angiogenic factor IL‐8. Additionally, the transition of melanoma cells from RGP to VGP is associated with overexpression of the transcription factors CREB and ATF‐1, both of which may act as survival factors for human melanoma cells. Inactivation of CREB/ATF‐1 activities in metastatic melanoma cells by dominant‐negative CREB or by anti‐ATF‐1 single chain antibody fragment (ScFv), resulted in deregulation of MMP‐2 and MCAM/MUC18, increased the sensitivity of melanoma cells to apoptosis, and inhibition of their tumorigenicity and metastatic potential in vivo. In this prospect article, we summarize our data on the role of AP‐2 and CREB/ATF‐1 in the progression of human melanoma and report on the development of new fully human antibodies anti‐MCAM/MUC18 and anti‐IL‐8 which could serve as new modalities for the treatment of melanoma. © 2004 Wiley‐Liss, Inc.
Structural and functional analysis of domains mediating interaction between NKX‐3.1 and PDEF
Authors: Chen Hui , Bieberich Charles J.
Published: November 2004

NKX‐3.1 is a suspected prostate tumor suppressor gene that encodes a homeodomain transcripti on factor. NKX‐3.1 has been demonstrated to interact with prostate derived Ets factor (PDEF) and to suppress the ability of PDEF to transactivate the prostate specific antigen promoter. To dissect the molecular basis of the interaction between these transcription factors, deletion analyses were preformed using the yeast two‐hybrid system. The interaction of NKX‐3.1 with full‐length PDEF requires part of the homeodomain and a tyrosine‐rich 21 amino acid sequence that lies C‐terminal to the homeodomain. The interaction of PDEF with full‐length NKX‐3.1 requires the Ets domain and a linker region that lies between the Ets and pointed domains. Deletion of the C‐terminal 21 amino acids of NKX‐3.1 completely disrupts the ability to suppress the transactivation function of PDEF in prostate tumor cells, demonstrating concordance between interaction in yeast and function in mammalian cells. These studies have identified novel protein–protein interaction domains within NKX‐3.1 and PDEF that operate in concert with their respective DNA binding domains to mediate functional interactions between these growth regulatory transcription factors. © 2004 Wiley‐Liss, Inc.
Electron microscopy of DNA replication in 3‐D: Evidence for similar‐sized replication foci throughout S‐phase
Authors: Koberna Karel , Ligasová Anna , Malínský Jan , Pliss Artem , Siegel Alan J. , Cvačková Zuzana , Fidlerová Helena , Mašata Martin , Fialová Markéta , Raška Ivan , Berezney Ronald
Published: November 2004

DNA replication sites (RS) in synchronized HeLa cells have been studied at the electron microscopic level. Using an improved method for detection following the in vivo incorporation of biotin‐16‐deoxyuridine triphosphate, discrete RS, or foci are observed throughout the S‐phase. In particular, the much larger RS or foci typically observed by fluorescence microscopic approaches in mid‐ and late‐S‐phase, are found to be composed of smaller discrete foci that are virtually identical in size to the RS observed in early‐S‐phase. Pulse‐chase experiments demonstrate that the RS of early‐S‐phase are maintained when chased through S‐phase and into the next cell generation. Stereologic analysis demonstrates that the relative number of smaller sized foci present at a given time remains constant from early through mid‐S‐phase with only a slight decrease in late‐S‐phase. 3‐D reconstruction of serial sections reveals a network‐like organization of the RS in early‐S‐phase and confirms that numerous smaller‐sized replication foci comprise the larger RS characteristic of late‐S‐phase. © 2004 Wiley‐Liss, Inc.
Evaluation of library ranking efficacy in virtual screening
Authors: Kontoyianni Maria , Sokol Glenn S. , MCclellan Laura M.
Published: November 2004

We present the results of a comprehensive study in which we explored how the docking procedure affects the performance of a virtual screening approach. We used four docking engines and applied 10 scoring functions to the top‐ranked docking solutions of seeded databases against six target proteins. The scores of the experimental poses were placed within the total set to assess whether the scoring function required an accurate pose to provide the appropriate rank for the seeded compounds. This method allows a direct comparison of library ranking efficacy. Our results indicate that the LigandFit/Ligscore1 and LigandFit/GOLD docking/scoring combinations, and to a lesser degree FlexX/FlexX, Glide/Ligscore1, DOCK/PMF (Tripos implementation), LigandFit1/Ligscore2 and LigandFit/PMF (Tripos implementation) were able to retrieve the highest number of actives at a 10% fraction of the database when all targets were looked upon collectively. We also show that the scoring functions rank the observed binding modes higher than the inaccurate poses provided that the experimental poses are available. This finding stresses the discriminatory ability of the scoring algorithms, when better poses are available, and suggests that the number of false positives can be lowered with conformers closer to bioactive ones. © 2004 Wiley Periodicals, Inc. J Comput Chem 26: 11–22, 2005
QMQSAR: Utilization of a semiempirical probe potential in a field‐based QSAR method
Authors: Dixon Steve , Merz Kenneth M. , Lauri Giorgio , Ianni James C.
Published: November 2004

A semiempirical quantum mechanical approach is described for the creation of molecular field‐based QSAR models from a set of aligned ligand structures. Each ligand is characterized by a set of probe interaction energy (PIE) values computed at various grid points located near the surface of the ligand. Single‐point PM3 calculations afford these PIE values, which represents a pool of independent variables from which multilinear regression models of activity are built. The best n‐variable fit is determined by constructing an initial regression using standard forward stepwise selection, followed by refinement using a simulated annealing technique. The resulting fit provides an easily interpreted 3D physical model of ligand binding affinity. Validation against three literature datasets demonstrates the ability of the semiempirical potential to model critical binding interactions in diverse systems. © 2004 Wiley Periodicals, Inc. J Comput Chem 26: 23–34, 2005
Involvement of the tumor necrosis factor (TNF)/TNF receptor system in leukemic cell apoptosis induced by histone deacetylase inhibitor depsipeptide (FK228)
Authors: Sutheesophon Krittaya , Nishimura Noriko , Kobayashi Yukiko , Furukawa Yutaka , Kawano Mikihiko , Itoh Kouichi , Kano Yasuhiko , Ishii Hideshi , Furukawa Yusuke
Published: November 2004

Inhibition of histone deacetylase (HDAC) is a novel strategy for the treatment of leukemias via restoration of aberrantly silenced genes. In this study, we conducted a detailed analysis of anti‐leukemic effects of an HDAC inhibitor (HDI), depsipeptide (FK228), using myeloid leukemia cell lines HL‐60 and K562. DNA chip analysis revealed upregulation of TNF‐α mRNA and a number of molecules involved in TNF‐signaling such as TRAF‐6, caspases‐10, and ‐7 in depsipeptide‐treated HL‐60 cells, which prompted us to examine the involvement of the TNF/TNF receptor system in the anti‐leukemic effects of the drug. Upregulation of TNF‐α was induced by depsipeptide in HL‐60 and K562 cells, which expressed type I TNF receptors (TNF‐RI). Depsipeptide activated caspases‐8 and ‐10, which in turn cleave caspases‐3 and ‐7, leading to apoptotic cell death in both cell lines. Anti‐TNF‐α neutralizing antibody and short interfering RNA (siRNA) against TNF‐RI alleviated the activation of the caspase cascade and the induction of apoptosis, indicating the presence of an autocrine loop. Finally, we demonstrated that the enhanced production of TNF‐α by depsipeptide was due to transcriptional activation of the TNF‐α gene through hyperacetylation of histones H3 and H4 in its promoter region (−208 to +35). These results suggest that autocrine production of TNF‐α plays a role in the cytotoxicity of depsipeptide against a subset of leukemias. © 2004 Wiley‐Liss, Inc.
Cell size‐dependent and independent proliferation of rodent neuroblastoma x glioma cells
Authors: Rouzaire‐Dubois Béatrice , O'regan Seana , Dubois Jean‐Marc
Published: November 2004

For decades, the connection between cell size and division has been the subject of controversy. While in yeast, cell size checkpoints coordinate cellular growth with cell‐cycle progression, it has been recently shown that large and small Schwann cells proliferate at the same rate (Conlon and Raff, 2003, J Biol 2:7). From this point of view, it is important to know whether normal and tumoral cells are similar. During continuous culture of NG108‐15 neuroblastoma x glioma cells, the rate of proliferation, cell size, and external pH changed in parallel. At constant pH, the cell size‐proliferation relationship followed a bell‐shaped curve, so that proliferation was optimal within a cell volume window. In contrast, external acidification decreased proliferation independently of cell size. Using electrophysiological techniques, we showed that changes in cell size were dependent on both the uptake of nutrients and the passive influx of ions. Furthermore, an increase in cell size was associated with an increase in total proteins/cell. Another way to influence cell growth and proliferation is to alter the activity of the PI‐3 kinase and target of rapamycin (TOR) signaling pathway. In NG108‐15 cells, pharmacological inhibition of these proteins with LY 294002 and rapamycin respectively decreased proliferation but did not modify cell size. In contrast, aphidicolin treated cells did not proliferate, but they continued to increase in size. Altogether these results indicate that the proliferation of NG108‐15 cells is controlled by both cell size‐dependent and independent mechanisms that include extracellular pH and PI‐3 kinase activity. © 2004 Wiley‐Liss, Inc.
Neuroimmunoprotective effects of estrogen and derivatives in experimental autoimmune encephalomyelitis: Therapeutic implications for multiple sclerosis
Authors: Offner Halina
Published: November 2004

The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17β‐estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. However, oral ethinyl estradiol (EE) and fluasterone, which lacks estrogenic side effects, could partially reverse clinical EAE when given after the onset of disease. The three main areas discussed in this review include E2‐mediated inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE were mediated throughEsr1(α receptor for E2) but notEsr2(β receptor for E2), as were its antiinflammatory and neuroprotective effects. A novel finding is that E2 up‐regulated the expression ofFoxp3and CTLA‐4 that contribute to the activity of CD4+CD25+Treg cells. The protective effects of E2 in EAE suggest its use as therapy for MS, although the risk of cardiovascular disease may complicate treatment in postmenopausal women. This risk could be minimized by using subpregnancy levels of exogenous E2 that produced synergistic effects when used in combination another immunoregulatory therapy. Alternatively, one might envision using EE or fluasterone metabolites alone or in combination therapies in both male and female MS patients. © 2004 Wiley‐Liss, Inc.
Alkyl substituted phenoxyl decay in a hydrogen transfer equilibrium
Authors: Coronel Marta E. J.
Published: November 2004

The kinetics of radical decay in the equilibrium: 2,4,6‐tri‐tert‐butylphenoxyl radical 1 + 2,6‐di‐tert‐butyl‐4‐methylphenol 2 = 2,4,6‐tri‐tert‐butylphenol 3 + 2,6‐di‐tert‐butyl‐4‐methylphenoxyl radical 4 was studied at 298 and 273 K by means of EPR spectroscopy. At 298 K second order prevails, whereas at 273 K the best fit was order 3/2. The extinction of 4 takes place in two steps: dimerization followed by disproportionation of the dimer, but the stable radical 1 enters in crossed dimerization with 4 to yield nonradical products. The mechanism ensures a constant [4]/[1] ratio along the decay. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 37: 1–4, 2005
The liquid‐phase oxidation of isomeric methoxy‐(1‐methylethyl)benzenes with oxygen to the hydroperoxides
Authors: Zawadiak Jan , Jakubowski Bartłomiej , Stec Zbigniew
Published: November 2004

The kinetics of liquid‐phase oxidation of 1‐methoxy‐2‐(1‐methylethyl)benzene (1a), 1‐methoxy‐3‐(1‐methylethyl)benzene (1b), and 1‐methoxy‐4‐(1‐methylethyl)benzene (1c) with oxygen as oxidant to yield the corresponding 1‐methyl‐1‐(2‐methoxyphenyl)ethyl (2a), 1‐methyl‐1‐(3‐methoxyphenyl)ethyl (2b), and 1‐methyl‐1‐(4‐methoxyphenyl)ethyl (2c) hydroperoxides was studied. The oxidizabilities of 1a, 1b, and 1c were established over the temperature range 50–120°C. The overall activation energies of oxidation were determined for 1b and 1c over the temperature range 50–120°C. Thermal stability of 2a and 2b and the initiating properties of hydroperoxides 2a, 2b, and 2c were studied. Long‐term noncatalytic oxidations of 1b and 1c to respective hydroperoxides were carried out. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 37: 10–16, 2005
Kinetic study of the oxidation of some catecholamines by digital simulation of cyclic voltammograms
Authors: Afkhami Abbas , Nematollahi Davood , Khalafi Lida , Rafiee Mohammad
Published: November 2004

Electrochemical oxidation of some catecholamines such as dopamine (1), L‐dopa (2), and methyldopa (3) has been studied in various pH values, using cyclic voltammetry. The results indicate participation of catecholamines (1–3) in intramolecular cyclization reaction to form the corresponding o‐quinone derivatives (1d–3d). In various pHs, based on ECE mechanism, the observed homogeneous rate constants (kobs) of cyclization reaction were estimated by comparing the experimental cyclic voltammetric responses with the digital‐simulated results. Also, the cyclization rate constants (kcyc) were calculated using microscopic acidic dissociation constant of ammonium groups. The significant differences in electrochemical behavior, kobs and kcyc, of L‐dopa (2) and methyldopa (3) with dopamine (1) are due to the effects of the side chain carboxyl group. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 37: 17–24, 2005
Experimental and modeling study of the oxidation of toluene
Authors: Bounaceur R. , Da Costa I. , Fournet R. , Billaud F. , Battin‐Leclerc F.
Published: November 2004

This paper describes an experimental and modeling study of the oxidation of toluene. The low‐temperature oxidation was studied in a continuous flow stirred tank reactor with carbon‐containing products analyzed by gas chromatography under the following experimental conditions: temperature from 873 to 923 K, 1 bar, fuel equivalence ratios from 0.45 to 0.91, concentrations of toluene from 1.4 to 1.7%, and residence times ranging from 2 to 13 s corresponding to toluene conversion from 5 to 85%. The ignition delays of toluene–oxygen–argon mixtures with fuel equivalence ratios from 0.5 to 3 were measured behind reflected shock waves for temperatures from 1305 to 1795 K and at a pressure of 8.7 ± 0.7 bar. A detailed kinetic mechanism has been proposed to reproduce our experimental results, as well as some literature data obtained in other shock tubes and in a plug flow reactor. The main reaction paths have been determined by sensitivity and flux analyses. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 37: 25–49, 2005
He-Ne (λ = 1.15 μ) laser with two orthogonally polarized modes
Authors: Gonchukov S , Lasarev Yu , Vakurov M , Yermachenko V
Published: November 2004

In view of its potential for the intracavity laser
refractometry, He-Ne laser with two orthogonally polarized modes
at wavelength of 1.15 μ was studied. The amplitude and
frequency characteristics of this laser were investigated
theoretically and experimentally. It has been shown that stable
two-mode lasing may be implemented for any split between modes
upon applying the transverse magnetic field.
Nuclear resonance spectroscopy of the 31-yr isomer of Hf-178
Authors: Collins C B , Zoita N C , Davanloo F , Yoda Y , Uruga T , Pouvesle J M , Popescu I I
Published: November 2004

Induced release of the high energy densities stored in
isomeric nuclear states may be important in the development of
ultrashort wavelength lasers. Such a release could compensate the
spontaneous power density radiated from the laser medium at
threshold. The most promising candidate for such a role seems to
be the 31-yr isomeric nucleus of Hf-178 that stores 1.3 GJ/g in
the electromagnetic excitation of its constituent protons and
neutrons. Successful studies of the induced release of energies
from such isomeric states have required an extension of techniques
for nuclear resonance spectroscopy using synchrotron radiation
(SR) that had previously been applied only to ground state
materials. In 2004, monochromatic X-rays from the SPring-8 SR
source were used to identify one of the excited nuclear states
that mediates the induced decay of the 31-yr isomer of Hf-178.
That ``trigger level'' was found to lie at 2457.20(22) keV. It was
excited when an isomeric nucleus absorbed an incident X-ray
photon. We found that one branch of its subsequent decay
consisted of a strong electromagnetic transition to the ground
state of the nucleus. The energy of the γ-photon emitted
was equal to the energy of the trigger level. Proximity in energy
of that level to the energy of 2446.06 keV stored by the isomer
makes it easy to induce a release of the stored energy and
encourages prospects for the development of a gamma ray laser.
Rubidium spectroscopy at 778–780 nm with a distributed
feedback laser diode
Authors: Kraft S , Deninger A , Trück C , Fortágh J , Lison F , Zimmermann C
Published: November 2004

We have performed high resolution spectroscopy of
rubidium with a single mode continuous wave distributed feedback
(DFB) laser diode. The saturation spectrum of the D2-line of
85Rb and 87Rb was recorded with a resolution close to
the natural line width. The emission frequency was actively
stabilized to Doppler-free transitions with a relative accuracy of
better than 7 parts in 109 using commercially available servo
devices only. An output power of 80 mW was sufficient to allow for
two-photon spectroscopy of the 5S-5D-transition of 87Rb.
Further, we report on the spectral properties of the DFB diode,
its tuning range and its frequency modulation properties. The line
width of the diode laser, determined with high resolution Doppler
free two photon spectroscopy, was 4 MHz without applying any
active stabilization techniques. For time scales below 5 μs
the line width drops below 2 MHz.
In vivo imaging of Malassezia yeasts on human skin using confocal laser
scanning microscopy
Authors: Meyer L E , Otberg N , Tietz H-J , Sterry W , Lademann J
Published: November 2004

Fiber-based confocal laser scanning microscopy affords
a vast field of application in medical research and clinical
practice. The application of fluorescent dye allows real-time
imaging of yeasts of the genus Malassezia on human skin in
vivo. An Ar+-laser is used to excite the fluorescent food dye
sodium fluorescein at 488 nm. Its emission is simultaneously
detected in the spectral region from 500–600 nm. Topically
applied fluorescein labels fungal microstructures in native
habitat. Cumulative intradermal injection of the same dye enables
a subsurface view of the underlying cutaneous area.

In the present paper, we report the ability of the combination of
in vivo confocal microscopy and sodium fluorescein
application to produce real-time and high-resolution images of
fungal structures on human skin. The obtained confocal images
demonstrate the micro architecture of superficial Malassezia
yeasts and corneocytes in horizontal plane. Taxonomic
classification into different Malassezia species and observation
of their colonisation patterns in native milieu brings new
conclusions to fungal skin behaviour and diseases. We demonstrate
advantages in clinical investigation practice over traditional
laboratory routine using this non-invasive imaging tool. The
described method opens new promising prospects and the possibility
for further studies in fungal research.
Novel Photo‐Alignment Polymer Layer Capable of Charge Transport
Authors: Lee Jaemin , Lee Jeong‐Ik , Sung Shi‐Joon , Chu Hye Yong , Park Jung‐Ki , Shim Hong‐Ku
Published: November 2004

Summary: With the progress of organic electronics, materials possessing various functionalities are attracting much attention. Here we have synthesized a novel photo‐alignment polymer composed of a conjugated carbazole main‐chain and a coumarin side‐chain through nickel(0)‐mediated polymerization. Carbazole is a well‐known hole transporting material and coumarin is also famous for its good photo‐alignment properties. The photochemical reactivity of the coumarin side‐chain was monitored by UV‐vis spectroscopy and the liquid crystal (LC) photo‐alignment direction of the polymer film was proved to be perpendicular to the polarization direction of the irradiated UV light. The highest occupied molecular orbital (HOMO) level of the polymer, measured from both cyclic voltammetry and photoelectron spectroscopy, was −5.32 eV. Organic light‐emitting diodes (OLEDs) of the configuration [ITO/polymer/NPB/Alq3/LiF/Al] showed a higher efficiency (2.17%) and brightness (14 000 cd · m−2) than a control device due to enhanced charge balance.

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Organic‐Inorganic Nanohybrids Obtained by Sequential Copolymerization of ε‐Caprolactone and L,L‐Lactide from Activated Clay Surface
Authors: Pollet Eric , Delcourt Cécile , Alexandre Michael , Dubois Philippe
Published: November 2004

Summary: We report here on the controlled grafting of defined copolyester chains directly onto the activated surface of MMT nanoplatelets dispersed in apolar medium. More precisely, monomers such as CL and LA were copolymerized, in dilute solution, by the well‐known coordination‐insertion ring‐opening mechanism initiated directly from the clay platelets. This method is based on the use of MMT organo‐modified by ammonium cations bearing hydroxyl functions. Using a surfactant mixture that contains varying proportions of hydroxyl‐substituted alkyl ammonium and non‐functionalized alkylammonium cations for exchanging the initial Na+ counterions of the natural clay allows preparing organoclays with a tunable amount of hydroxyl functions on their surface. These hydroxyl functions can then easily be derivatized into aluminium alkoxides in order to initiate the polymerization directly from the surface of clay swollen in an organic solvent like toluene. The resulting activated organo‐clays proved to promote efficiently the block copolymerization of CL and LA in solution. The results demonstrate that adjusting the parameters allows to control the process. Indeed, the growing copolyester chains are effectively surface‐anchored onto the clay and their average length and grafting density can readily be modulated by the available amount of OH functions on the MMT platelets. These new organic‐inorganic nanohybrid materials present nearly exfoliated morphologies and the grafted copolymers display a semi‐crystalline and blocky structure as attested by DSC and NMR analyses, respectively.

TEM photograph of the recovered nanohybrid based on poly[CL‐block‐LA] diblock copolyester grafted onto Cloisite®30B surface.

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TEM photograph of the recovered nanohybrid based on poly[CL‐block‐LA] diblock copolyester grafted onto Cloisite®30B surface.
Flame Retardant Mechanisms of Red Phosphorus and Magnesium Hydroxide in High Impact Polystyrene
Authors: Braun Ulrike , Schartel Bernhard
Published: November 2004

Summary: The flame retardant mechanisms of red phosphorus, magnesium hydroxide and red phosphorus combined with magnesium hydroxide were studied in high impact polystyrene by means of comprehensive decomposition studies and combustion tests. The study is intended to illuminate prerequisites and the potential of red phosphorus as a fire retardant for hydrocarbon polymers in the condensed phase and in the gas phase. Thermal and thermo‐oxidative decomposition, decomposition kinetics and the product gases evolved were characterized using thermogravimetry coupled with Fourier transform infrared spectroscopy and mass spectroscopy, respectively. Fire behaviour was investigated with a cone calorimeter using different external heat fluxes, whereas the flammability was determined by limited oxygen indices. The combustion residues were analysed using XPS. Red phosphorus reduced the heat release in HIPS due to radical trapping in the gas phase. Magnesium hydroxide influenced fire behaviour by heat sink mechanisms, release of water and the formation of a magnesia layer acting as a barrier. The combination of both flame retardants in HIPS nearly resulted in a superposition. A slight synergy in barrier characteristics was due to the formation of magnesium phosphate, whereas a slight anti‐synergism occurred in flammability and in the gas phase action. The latter effect is controlled by a decreased fuel rate due to the barrier layer rather than by an initiation of red phosphorus oxidation in the condensed phase.

Heat release rate and total heat release at various external heat fluxes for HIPS (dotted = 70 kW · m−2, dashed = 50 kW · m−2, solid = 30 kW · m−2).

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Heat release rate and total heat release at various external heat fluxes for HIPS (dotted = 70 kW · m−2, dashed = 50 kW · m−2, solid = 30 kW · m−2).
Cover Picture: Macromol. Chem. Phys. 16/2004
Authors: Venkatesh Rajan , Yajjou Latifa , Koning Cor E , Klumperman Bert
Published: November 2004

Cover: The background image is an AFM micrograph of the poly(BIEM)‐graft‐poly(MA‐co‐octene) brushes on mica (height and phase). The SEC traces show the relatively small increase in hydrodynamic volume upon grafting of the side chains via ATRP, which points at the densely grafted nature of the architectures.

Further details can be found in the Full paper by R. Venkatesh, L. Yajjou, C. E. Koning, and B. Klumperman* on page 2161.
Poly(ε‐caprolactone)‐Based Organogels and Hydrogels with Poly(ethylene glycol) Cross‐Linkings
Authors: Coudane Jean , Laurent Elisabeth , Vert Michel
Published: November 2004

Summary: The reaction of triphosgene with poly(ethylene glycol) yielded poly(ethylene glycol) dichloroformate. This difunctional cross‐linker was allowed to react with poly(ε‐caprolactone) bearing carbanionic sites obtained by activation with lithium diisopropylamide. The reaction resulted in the cross‐linking of poly(ε‐caprolactone) chains by poly(ethylene glycol) segments, giving copolymer networks that gel in both organic and aqueous media.

Schematic of the PCL‐g‐PEG copolymers synthesized here.

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Schematic of the PCL‐g‐PEG copolymers synthesized here.