bluuebunny/crossref_metadata_2025 huggingface dataset:
13C Nuclear Magnetic Resonance Spectra of Organic Sulfur Compounds: Cyclic Sulfides, Sulfoxides, Sulfones, and Thiones
Authors: Chauhan M. S. , Still I. W. J.
Published: May 2006

13C Chemical shift data have been obtained for more than 50 thiochromanone and related sulfoxide and sulfone derivatives. The assignments of the various resonances in the most important of these have been made using the limited data already available and also by comparison with certain model compounds, such as thioanisole, diphenyl sulfide, and the corresponding sulfoxides and sulfones.Within each of these three series and in a fourth which comprises derivatives of thiochromone, including three α, β-unsaturated thiones, we have examined the effects on 13C chemical shift of substitution at various positions in the thiochromanone skeleton. Among the substituents examined in this context are methyl, phenyl, methoxyl, bromine, and carbomethoxyl. Attempts to compare the 13C chemical shifts for the thiochromanone series with those in a few oxygen containing analogs and in a small number of structurally similar analogs are also discussed.
The Crystal and Molecular Structures of the 3,5-Dimethylpyrazolylgallium dimethyl dimer, [Me2Ga·N2C5H7]2, and the Hydroxy-bridged Species, [Me2Ga(OH)(N2C5H7)GaMe2·2N2C5H8]
Authors: Rendle David F. , Storr Alan , Trotter James
Published: May 2006

Crystals of the 3,5-dimethylpyrazolylgallium dimethyl dimer [Me2Ga·N2C5H7]2 (1a) are monoclinic, a = 8.660(3), b = 13.776(1), c = 8.443(2) Å, β = 112.45(2)°, Z = 2, space group P21/c, and crystals of the hydroxy-bridged species [Me2Ga(OH)(N2C5H7)GaMe2·2N2C5H8] (1b) are monoclinic, a = 28.778(3), b = 9.098(3), c = 20.222(2) Å, β = 100.72(1)°, Z = 8, space group C2/c. Both structures were solved by Patterson and Fourier methods and were refined by full-matrix least-squares methods to final R values of 0.071 and 0.045 for 1443 and 2746 reflections with I ≥ 3σ(I) respectively. Molecules of 1a lie on crystallographic centers of symmetry, the central Ga—(N—N)2—Ga ring being almost planar as a result of steric interactions between gallium-methyl groups and those on the 'pyrazolyl' rings. The mean Ga—N and Ga—C distances are 1.993 Å and 1.962 Å respectively. Compound 1b was formed by the attack of moisture on the strained dimer 1a. The central feature is a five-membered Ga2N2O ring, with two 3,5-dimethylpyrazoie molecules hydrogen-bonded to it (N—H … O, O—H … N, 2.851 and 2.892 Å) and to each other (N—H … N, 2.907 Å). The five-membered ring adopts a slightly distorted envelope conformation, the angle between the Ga2N2 and N2O moieties being 13.9°. The mean Ga—N and Ga—O distances are 1.989 and 1.934 Å respectively.
The Preparation and Synthetic Utility of tert-Butyldiphenylsilyl Ethers
Authors: Hanessian Stephen , Lavallee Pierre
Published: May 2006

The utility of tert-butyldiphenylsilyl chloride as a reagent for the protection of hydroxyl groups was explored. The corresponding tert-BDPSi ethers have much greater stability to acids, and under conditions of hydrogenolysis, than related silyl and trityl ethers. Preferential removal of trityl, tetrahydropyranyl, benzyl, and other silyl ethers and acetals can be effected in presence of tert-EDPSi ethers. Treatment with fluoride ion causes smooth cleavage of the latter.
Reduction of Some Alkylisoxazoles with Lithium Aluminum Hydride
Authors: Khurana A. L. , Unrau A. M.
Published: May 2006

Lithium aluminum hydride reduction of alkyl substituted isoxazoles gave a variety of products. The major constituent was identified (i.r., n.m.r., m.s.) as hydroxyethylaziridine. Specifically, reduction of 3,4,5-trimethylisoxazole gave as the major product 2,3-dimethyl-3-β-hydroxyethylaziridine. Two of the more prominent minor products were identified as 2,3-dimethyl-3-ethylaziridine and 4-amino-3-methyl-2-pentanol. The corresponding products were identified when 3,5-dimethylisoxazole was reduced with LAH.
The Importance of Anharmonicity of The Vibrational Excited States in Chemical Kinetics
Authors: Bron Jan
Published: May 2006

The corrections to rate constants for an harmonicity of vibrational excited states have been evaluated over the temperature range of 200–1100 K. The reaction O2 + X, where X is H or D, has been chosen as the model system. Only the influence of vibrational anharmonicity of the triatomic transition state has been determined. Two geometric shapes for the transition state, bent and isosceles configurations, have been investigated in detail by the bond order method.It is found that the correction can be large, depending upon the geometry and force field of the transition state and the temperature. The magnitude of the correction for anharmonicity of the vibrational excited states depends mainly, at a particular temperature, on the strength of the O—X bond in the transition state. In the case of a large correction, anharmonicity may lead to a nonlinear Arrhenius plot.Because of cancellation effects, the correction for anharmonicity of the excited vibrational states in kinetic isotope effects can be ignored in the lower temperature region. It has also been found that anharmonicity of the vibrational groundstate can explain unexpected large isotope effects.
Oxilorphan and Butorphanol. Potent Narcotic Antagonists and Nonaddicting Analgesics in the 3,14-Dihydroxymorphinan Series. Part V
Authors: Monkovic Ivo , Wong Henry , Pircio Anthony W. , Perron Yvon G. , Pachter Irwin J. , Belleau Bernard
Published: May 2006

A series of 3,14-dihydroxymorphinans 8 was synthesized via a method of (a) acylation of 3-methoxy-Δ8,14-morphinan 4a (b) stereospecific epoxidation of the resultant amides to β-epoxides 5 (c) simultaneous reduction of amide and epoxide functions and (d) demethylation of the resultant 3-methoxy-14-hydroxymorphinans 7. Alternatively deblocking of the amine function in 5b by hydrolysis followed by reduction of the resultant amino epoxide 5e afforded 14-hydroxy-3-methoxymorphinan 7e, which is readily alklyated and demethylated to give various 8. On a basis of interesting pharmacological profiles compounds l-8c (oxilorphan) and l-8d (butorphanol) were selected for clinical studies.
Hydrogen–Water Deuterium Exchange Over Metal Oxide Promoted Nickel Catalysts
Authors: Sagert Norman H. , Shaw-Wood Paul E. , Pouteau Rita M. L.
Published: May 2006

Specific rates have been measured for hydrogen–water deuterium isotope exchange over unsupported nickel promoted with about 20% of various metal oxides. The oxides used were Cr2O3, MoO2, MnO, WO2−WO3, and UO2. Nickel surface areas, which are required to measure the specific rates, were determined by hydrogen chemisorption. Specific rates were measured as a function of temperature in the range 353 to 573 K and as a function of the partial pressure of hydrogen and water over a 10-fold range of partial pressure.The molybdenum and tungsten oxides gave the highest specific rates, and manganese and uranium oxides the lowest. Chromium oxide was intermediate, although it gave the highest rate per gram of catalyst. The orders with respect to hydrogen and water over molybdenum oxide and tungsten oxide promoted nickel were consistent with a mechanism in which nickel oxide is formed from the reaction of water with the catalyst, and then is reduced by hydrogen. Over manganese and uranium oxide promoted catalysts, these orders are consistent with a mechanism in which adsorbed water exchanges with chemisorbed hydrogen atoms on the nickel surface. Chromium oxide is intermediate. It was noted that those oxides which favored the nickel oxide route had electronic work functions closest to those of metallic nickel and nickel oxide.
Librations Around the C(S)—Phenyl Bond in N-Thiobenzoylmorpholines Observed by 220 MHz Proton Magnetic Resonance Spectroscopy
Authors: Fulea Adrian O. , Krueger Peter J.
Published: May 2006

The 220 MHz p.m.r. spectra of 4-(4′-nitrothiobenzoyl)-2,6-dimethylmorpholine (1) provide evidence for the progressive freezing of the librations of the thioamide group around the C(S)—Ph bond as the temperature is lowered. This is supported by spectral data on related compounds in which the aromatic and hetero-ring substituents are altered.
13C Fourier Transform Nuclear Magnetic Resonance. XI. Pyridine N-Oxide Derivatives
Authors: Cushley Robert J. , Naugler David , Ortiz Carlos
Published: May 2006

Formation of the N-oxide for several pyridine derivatives results in a large upfield shift of the 2-, 4-, and 6-carbons and a significant downfield shift of the 3- and 5-carbons. The chemical shifts (Δδ) are consistent with a resonance and electric field mechanism. Molecular orbital calculations using CNDO/2 show a qualitative correlation between excess charge density and Δδ.
Hindered Internal Rotation About Aryl C—N Bonds in Aryl Substituted Heterocyclic Compounds: 3-Aryl-2-benzyl-4(3H)-quinazolinones
Authors: Colebrook Lawrence D. , Giles H. Gwynne
Published: May 2006

The proton magnetic resonance spectra of a number of 3-aryl substituted 2-benzyl-4(3H) quinazolinones indicate that internal rotation about the aryl C—N bond is highly hindered. Substantial free energy barriers (18.9–19.8 kcal/mol) have been measured even when the aryl groups lack bulky ortho substituents.
The Preparation of Some Hydridotricyclohexylphosphine Platinum(II) Complexes
Authors: Attig Thomas G. , Clark Howard C.
Published: May 2006

The reaction of the platinum(II) hydride containing bulky tricyclohexylphosphine ligands, trans-PtHCl(PCy3)2, PCy3 = tricyclohexylphosphine, with AgPF6 in methanol affords the air-stable cationic hydrido complex [trans-PtH(CH3OH)(PCy3)2]+PF6−, 1, The reaction of 1 with a number of neutral molecules, L, leads to simple substitution of the coordinated methanol molecule by L. The reaction of 1 with terminal acetylenes in methanol affords hydrido–methoxycarbene complexes rather than vinylic derivatives. The role of the bulky tricyclohexylphosphine ligand in these reactions is discussed. The reactions of 1 are compared to those of cationic platinum(II) hydrides containing other phosphines.
A New Mode of Photorearrangement in the Azoxybenzene Series
Authors: Bunce Nigel J.
Published: May 2006

Both isomers of 4-methoxyazoxybenzene photorearrange to the same o-hydroxyazo compound. In the case of β-4-methoxyazoxybenzene, prior photoisomerization to the α-isomer is involved.
Organic Sulfur Mechanisms. 17. A Brief Study of the Photolysis of an Unsaturated Cyclic Sulfone
Authors: King J. F. , Lewars E. G. , Harding D. R. K. , Enanoza R. M.
Published: May 2006

Photolysis of 3-phenyl-2H-thiopyran 1,1-dioxide (3) in methanol gives a mixture of 3-phenyl-5-methoxy-5,6-dihydro-2H-thiopyran 1,1-dioxide (4) and methyl 4-phenyl-2,4-pentadiene-1-sulfonate (5). Formation of 5 shows that the photochemical ring opening of cyclohexadienic sulfonyl compounds (1) does not require an atom bearing a free electron pair in the heterocyclic ring, and therefore argues in favor of a mechanism involving cycloreversion to the sulfene (1 → 2).
Reactions of Sodium Tetrahydroborate and Cyanotrihydroborate with Rhodium(I), (II), and (III) Systems in the Presence of Tertiary Phosphines
Authors: Holah David G. , Hughes Alan N. , Hui Benjamin C.
Published: May 2006

The nitrogen atmosphere reactions of phosphine–Rh(I), Rh(II), and Rh(III) chloride systems with NaBH4 and NaBH3CN and also similar reactions of [RhCl(CO)2]2 in the presence of phosphines are reported. Among the interesting products formed in the various reactions are hydrido, tetrahydroborato, hydrido–tetrahydroborato and hydrido–cyanotrihydroborato complexes such as the highly unstable Rh(I) species Rh(BH4)(PPh3)2, the much more stable Rh(II) complex RhH(BH4)(o-tolyl3P), the Rh(III)–5-phenyl-5H-dibenzophosphole (DBP) complex RhH2Cl(DBP)3, and the Rh(III) complex RhH2(BH3CN)(PPh3)3. Complexes of Rh(I) with BH3CN and additional CO and N2 ligands are also reported. These results are briefly discussed in the context of the previously proposed mechanism for the reaction of tetrahydroborate ion with Co, Ni, and Cu halides in the presence of phosphine ligands.
A General, Selective Synthesis of Thiol Esters
Authors: Masamune Satoru , Kamata Susumu , Diakur James , Sugihara Yoshikazu , Bates Gordon S.
Published: May 2006

Use of diethyl phosphorochloridate and Tl(I) thiolates constitutes a general, selective synthesis of thiol esters. Primary, secondary, and tertiary alkane- and arenethiols of various carboxylic acids, including those containing hydroxy groups have been prepared under mild conditions.
The Redox Behavior of 9,10-Anthraquinone-2-sulfonate in Acidic Aqueous Solution
Authors: Broadbent Arthur D. , Melanson Ronald J.
Published: May 2006

A green intermediate, observed during reduction of 9,10-anthraquinone-2-sulfonate (A) to the corresponding anthrahydroquinone (AH2) in acidic aqueous solution, has been identified as a quinhydrone-like charge-transfer complex of A and AH2. Spectrophotometric and potentiometric measurements have shown that changes in the slope of the potentiometric titration curves with varying initial [A] are caused only by this complex [Formula: see text]and not by any semiquinone radical (AH·) or radical anion (A·−) intermediate. The very low semiquinone formation constant in acidic solution indicates that the pKa of AH· < 7.0. Electrochemically determined pKa values for similar radicals in the range 8.5–10.5 are invalid because of interference by charge-transfer complexes of this type.
Stereodynamic Investigation of Dibenzo-1,5-cyclooctadiene and 5,6,11,12-tetrahydrodibenzo[b,f] [1,4]diazocine Derivatives
Authors: Sauriol-Lord Françoise , St-Jacques Maurice
Published: May 2006

A dynamic n.m.r. study of a deuterated derivative of dibenzo-1,5-cyclooctadiene (2-d4), N,N′-diniethyl-1,4-diazocine 3, and N,N′-diacetyl-1,4-diazocine (4) is reported. Two spectral changes of different origin are observed for 2-d4, one for 3 and three for 4. The results reveal the presence of a mixture of chair and twist-boat conformations for 2-d4 and 4, while the single spectral change observed for 3 is interpreted in terms of a single twist-boat form. Interconversion pathways are suggested to explain the characteristic behavior of each compound investigated.
The Temperature Dependence of Raman Band Parameters for Aquated Mg(II) and Zn(II)
Authors: Bulmer J. Timothy , Irish Donald E. , Ödberg Lars
Published: May 2006

The weak polarized Raman bands, previously assigned to the v1 mode of the octahedral species Mg(H2O)62+ and Zn(H2O)62+, have been studied over the temperature ranges −32 to 99 °C and −29 to 80 °C respectively. The signal-to-noise ratio has been enhanced by multi-scan averaging with a spectrometer interfaced to a PDP/11 computer. The digitized band profiles have been examined analytically to extract these parameters: position of maximum, position of centroid, full width at half height (f.w.h.h.), and intensity. The dependence on concentration and acidity has also been measured. Whereas the 390 cm−1 line of aquated zinc(II) shifts only 3 cm−1 to lower frequencies and broadens by about 16 cm−1 for a 110 °C temperature increase, the 362 cm−1 band of aquated magnesium(II) shifts down by 15 cm−1 but broadens to the same extent for a 130 °C temperature increase. The results are interpreted in terms of the difference in the magnitude of forces between these cations and hydrated water molecules.
Mechanism of inhibition of TREK-2 (K2P10.1) by the Gq-coupled M3muscarinic receptor
Authors: Kang Dawon , Han Jaehee , Kim Donghee
Published: May 2006

TREK-2 is a member of the two-pore domain K+channel family and provides part of the background K+current in many types of cells. Neurotransmitters that act on receptors coupled to Gqstrongly inhibit TREK-2 and thus enhance cell excitability. The molecular basis for the inhibition of TREK-2 was studied. In COS-7 cells expressing TREK-2 and M3receptor, acetylcholine (ACh) applied to the bath solution strongly inhibited the whole cell current, and this was markedly reduced in the presence of U-73122, an inhibitor of PLC. The inhibition was also observed in cell-attached patches when ACh was applied to the bath solution. In inside-out patches, direct application of guanosine 5′- O-(3-thiotriphosphate) (10 μM), Ca2+(5 μM), or diacylglycerol (DAG; 10 μM) produced no inhibition of TREK-2 in >75% of patches tested. Phosphatidic acid, a product of DAG kinase, had no effect on TREK-2. Pretreatment of cells with 20 μM wortmannin, an inhibitor of phosphatidylinositol kinases, did not affect the inhibition or the recovery from inhibition of TREK-2, suggesting that phosphatidylinositol 4,5-bisphosphate depletion did not mediate the inhibition. Pretreatment of cells with a protein kinase C inhibitor (bisindolylmaleimide, 10 μM) markedly inhibited ACh-induced inhibition of TREK-2. Mutation of two putative PKC sites (S326A, S359C) abolished inhibition by ACh. Mutation of these amino acids to aspartate to mimic the phosphorylated state resulted in diminished TREK-2 current and no inhibition by ACh. These results suggest that the agonist-induced inhibition of TREK-2 via M3receptor occurs primarily via PKC-mediated phosphorylation.
Saccade-Related Spread of Activity Across Superior Colliculus May Arise From Asymmetry of Internal Connections
Authors: Nakahara Hiroyuki , Morita Kenji , Wurtz Robert H. , Optican Lance M.
Published: May 2006

The superior colliculus (SC) receives a retinotopic projection of the contralateral visual field in which the representation of the central field is expanded with respect to the peripheral field. The visual projection forms a nonlinear, approximately logarithmic, map on the SC. Models of the SC commonly assume that the function defining the strength of neuronal connections within this map (the kernel) depends only on the distance between two neurons, and is thus isotropic and homogeneous. However, if the connection strength is based on the distance between two stimuli in sensory space, the kernel will be asymmetric because of the nonlinear projection onto the brain map. We show, using a model of the SC, that one consequence of these asymmetric intrinsic connections is that activity initiated at one point spreads across the map. We compare this simulated spread with the spread observed experimentally around the time of saccadic eye movements with respect to direction of spread, differing effects of local and global inhibition, and the consequences of localized inactivation on the SC map. Early studies suggested that the SC spread was caused by feedback of eye displacement during a saccade, but subsequent studies were inconsistent with this feedback hypothesis. In our new model, the spread is autonomous, resulting from intrinsic connections within the SC, and thus does not depend on eye movement feedback. Other sensory maps in the brain (e.g., visual cortex) are also nonlinear and our analysis suggests that the consequences of asymmetric connections in those areas should be considered.
The Combination of the Proteasome Inhibitor Bortezomib and the Bcl-2 Antisense Molecule Oblimersen Sensitizes Human B-Cell Lymphomas to Cyclophosphamide
Authors: O'Connor Owen A. , Smith Emily A. , Toner Lorraine E. , Teruya-Feldstein Julie , Frankel Stanley , Rolfe Mark , Wei Xiaohui , Liu Shujun , Marcucci Guido , Chan Kenneth K. , Chanan-Khan Asher
Published: May 2006

Purpose: To determine whether the combination of the proteasome inhibitor bortezomib and the bcl-2 antisense molecule oblimersen can sensitize human lymphoma to cyclophosphamide.

Experimental Design: Cytotoxicity assays were conducted to determine if there was any additive or synergistic interaction between the combinations of bortezomib, oblimersen, and cyclophosphamide using a standard trypan blue exclusion assay. Based on these experiments, in vivo experiments in severe combined immunodeficiency beige mice were done using human lymphoma xenografts in which different schedules were explored. Bcl-2 and oblimersen levels were determined in treated tumors, some of which were resected at the end of the in vivo experiment and evaluated pathologically.

Results: The results suggest that the combination of bortezomib and oblimersen seem to interact in at least an additive fashion, and that the addition of cyclophosphamide to this drug combination can markedly improve tumor cell kill. In addition, it seems that these drug combinations may be schedule-dependent, with a requirement for oblimersen pretreatment. Animals treated with the triplet drug combination in a schedule-dependent manner experienced pathologic complete regression of disease, which was not observed in other treatment cohorts. The addition of bortezomib also seemed to increase the levels of intracellular oblimersen, which resulted in a marked reduction in Bcl-2. Histologic studies confirmed marked necrosis and caspase-3 activation only in the cohort receiving all three drugs.

Conclusion: The use of Bcl-2-directed therapy and a proteasome inhibitor sensitizes human lymphoma cells to cytotoxic drugs like cyclophosphamide. This combination may offer new opportunities for integrating novel targeted therapies with conventional chemotherapy.
Tumor-Driven Paracrine Platelet-Derived Growth Factor Receptor α Signaling Is a Key Determinant of Stromal Cell Recruitment in a Model of Human Lung Carcinoma
Authors: Tejada Max L. , Yu Lanlan , Dong Jianying , Jung Kenneth , Meng Gloria , Peale Franklin V. , Frantz Gretchen D. , Hall Linda , Liang XiaoHuan , Gerber Hans-Peter , Ferrara Napoleone
Published: May 2006

Activated fibroblasts are thought to play important roles in the progression of many solid tumors, but little is known about the mechanisms responsible for the recruitment of fibroblasts in tumors. Using several methods, we identified platelet-derived growth factor A (PDGFA) as the major fibroblast chemoattractant and mitogen from conditioned medium generated by the Calu-6 lung carcinoma cell line. In addition, we showed that Calu-6 tumors express significant levels of PDGFC, and that the levels of expression of these two PDGFRα ligands correlate strongly with the degree of stromal fibroblast infiltration into the tumor mass. The most intense expression of PDGFRα was observed in fibroblasts in the tumor outer rim. We subsequently showed that disrupting PDGFRα-mediated signaling results in significant inhibition of tumor growth in vivo. Furthermore, analysis of a compendium of microarray data revealed significant expression of PDGFA, PDGFC, and PDGFRα in human lung tumors. We propose that therapies targeting this stromal cell type may be effective in treating certain types of solid tumors.
Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases
Authors: Varga Zsuzsanna , Theurillat Jean-Philippe , Filonenko Valeriy , Sasse Bernd , Odermatt Bernhard , Jungbluth Achim A. , Chen Yao-Tseng , Old Lloyd J. , Knuth Alexander , Jäger Dirk , Moch Holger
Published: May 2006

Purpose: NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1.

Methods: In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases.

Results: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor–positive and lymph node–negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1 expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1 positive.

Conclusion: This study supports the notion that NY-BR-1 is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.
Ectopic Expression of the Proto-oncogene Mer in Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Graham Douglas K. , Salzberg Dana B. , Kurtzberg Joanne , Sather Susan , Matsushima Glenn K. , Keating Amy K. , Liang Xiayuan , Lovell Mark A. , Williams Sara A. , Dawson Thomas L. , Schell Michael J. , Anwar Adil A. , Snodgrass H. Ralph , Earp H. Shelton
Published: May 2006

Purpose: The Mer receptor tyrosine kinase, cloned from a B-lymphoblastoid library, is the mammalian orthologue of the chicken retroviral oncogene v-eyk and sends antiapoptotic and transforming signals when activated. To determine if Mer expression is ectopic in T-cell acute lymphoblastic leukemia (ALL) and potentially important in leukemogenesis, we analyzed Mer expression in normal human thymocytes and lymphocytes and in pediatric ALL patient samples.

Experimental Design: Reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to determine expression of Mer in sorted human thymocyte populations, lymphocytes, and lymphocytes activated by phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. Mer expression in 34 T-cell ALL (T-ALL) patient samples was evaluated by reverse transcription-PCR, and Mer protein expression in a separate cohort of 16 patient samples was assayed by flow cytometry and Western blot.

Results: Mer expression was absent in normal thymocytes or lymphocytes, and in T cells activated with phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. In contrast, Jurkat cells and T-ALL patient samples expressed unique 180 to 185 kDa Mer protein glycoforms. Substantial Mer RNA levels were principally observed in a subset of T-ALL patient samples that expressed B220 (P = 0.004) but lacked surface expression of CD3 (P = 0.02) and CD4 (P = 0.006), a phenotypic profile consistent with immature lymphoblasts. In addition, 8 of 16 T-ALL patient samples had Mer protein detected by flow cytometry and Western blot.

Conclusions: Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal Mer expression may be a novel therapeutic target in pediatric ALL therapy.
Identification of HLA-A2- or HLA-A24-Restricted CTL Epitopes Possibly Useful for Glypican-3-Specific Immunotherapy of Hepatocellular Carcinoma
Authors: Komori Hiroyuki , Nakatsura Tetsuya , Senju Satoru , Yoshitake Yoshihiro , Motomura Yutaka , Ikuta Yoshiaki , Fukuma Daiki , Yokomine Kazunori , Harao Michiko , Beppu Toru , Matsui Masanori , Torigoe Toshihiko , Sato Noriyuki , Baba Hideo , Nishimura Yasuharu
Published: May 2006

Purpose and Experimental Design: We previously reported that glypican-3 (GPC3) was overexpressed, specifically in hepatocellular carcinoma (HCC) and melanoma in humans, and it was useful as a novel tumor marker. We also reported that the preimmunization of BALB/c mice with dendritic cells pulsed with the H-2Kd-restricted mouse GPC3298-306 (EYILSLEEL) peptide prevented the growth of tumor-expressing mouse GPC3. Because of similarities in the peptide binding motifs between H-2Kd and HLA-A24 (A*2402), the GPC3298-306 peptide therefore seemed to be useful for the immunotherapy of HLA-A24+ patients with HCC and melanoma. In this report, we investigated whether the GPC3298-306 peptide could induce GPC3-reactive CTLs from the peripheral blood mononuclear cells (PBMC) of HLA-A24 (A*2402)+ HCC patients. In addition, we used HLA-A2.1 (HHD) transgenic mice to identify the HLA-A2 (A*0201)–restricted GPC3 epitopes to expand the applications of GPC3-based immunotherapy to the HLA-A2+ HCC patients.

Results: We found that the GPC3144-152 (FVGEFFTDV) peptide could induce peptide-reactive CTLs in HLA-A2.1 (HHD) transgenic mice without inducing autoimmunity. In five out of eight HLA-A2+ GPC3+ HCC patients, the GPC3144-152 peptide-reactive CTLs were generated from PBMCs by in vitro stimulation with the peptide and the GPC3298-306 peptide-reactive CTLs were also generated from PBMCs in four of six HLA-A24+ GPC3+ HCC patients. The inoculation of these CTLs reduced the human HCC tumor mass implanted into nonobese diabetic/severe combined immunodeficiency mice.

Conclusion: Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for a large number of HCC patients.
Inflammatory Biomarkers for Persistent Fatigue in Breast Cancer Survivors
Authors: Collado-Hidalgo Alicia , Bower Julienne E. , Ganz Patricia A. , Cole Steve W. , Irwin Michael R.
Published: May 2006

Purpose: This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast cancer survivors.

Experimental Design: Leukocyte subsets, plasma inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited ≥2 years after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker of fatigue risk.

Results: Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-α following lipopolysaccharide stimulation, elevated plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69+ T lymphocytes, as highly diagnostic of fatigue (P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83).

Conclusion: These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.
PUMA Sensitizes Lung Cancer Cells to Chemotherapeutic Agents and Irradiation
Authors: Yu Jian , Yue Wen , Wu Bin , Zhang Lin
Published: May 2006

Purpose: Lung cancer, the leading cause of cancer mortality worldwide, is often diagnosed at late stages and responds poorly to conventional therapies, including chemotherapy and irradiation. A great majority of lung tumors are defective in the p53 pathway, which plays an important role in regulating apoptotic response to anticancer agents. PUMA was recently identified as an essential mediator of DNA damage–induced and p53-dependent apoptosis. In this study, we investigated whether the regulation of PUMA by anticancer agents is abrogated in lung cancer cells and whether PUMA expression suppresses growth of lung cancer cells and/or sensitizes lung cancer cells to chemotherapeutic agents and irradiation through induction of apoptosis.

Experimental Designs: The expression of PUMA was examined in lung cancer cells with different p53 status treated with chemotherapeutic agents. An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents or γ-irradiation, was used to treat lung cancer cells. The growth inhibitory and apoptotic effects of PUMA in vitro and in vivo were examined. The mechanisms of PUMA-mediated growth suppression and apoptosis were investigated through analysis of caspase activation and release of mitochondrial apoptogenic proteins. The cytotoxicities of PUMA on cancer and normal/nontransformed cells were compared. The efficacy of PUMA and p53 in suppressing the growth of lung cancer cells was also compared.

Results: We showed that the induction of PUMA by chemotherapeutic agents is abolished in p53-deficient lung cancer cells. PUMA expression resulted in potent growth suppression of lung cancer cells and suppressed xenograft tumor growth in vivo through induction of apoptosis. Low dose of Ad-PUMA significantly sensitized lung cancer cells to chemotherapeutic agents and γ-irradiation through induction of apoptosis. The effects of PUMA are mediated by enhanced caspase activation and release of cytochrome c and apoptosis-inducing factor into the cytosol. Furthermore, PUMA seems to be selectively toxic to cancer cells and more efficient than p53 in suppressing lung cancer cell growth.

Conclusions: Our findings indicate that PUMA is an important modulator of therapeutic responses of lung cancer cells and is potentially useful as a sensitizer in lung cancer therapy.
Sublethal Irradiation Induces Vascular Endothelial Growth Factor and Promotes Growth of Hepatoma Cells: Implications for Radiotherapy of Hepatocellular Carcinoma
Authors: Chung Yih-Lin , Jian James Jer-Min , Cheng Skye Hongiun , Tsai Stella Y.C. , Chuang Vincent P. , Soong Thomas , Lin Yu-Mong , Horng Cheng-Fang
Published: May 2006

Purpose: To investigate the clinical benefit of additional radiotherapy to patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE) and the molecular effects of radiation on gene expression in hepatoma cells.

Experimental Design: Between August 1996 and August 2003, 276 and 64 patients with American Joint Committee on Cancer stage T3N0M0 hepatocellular carcinoma receiving TACE alone and TACE followed by three-dimensional conformal radiotherapy, respectively, at our institution were studied. Clinical outcome and pattern of failure were analyzed for the association of survival benefit with radiotherapy. The molecular effects of radiotherapy were studied in vitro and in vivo using human hepatoma cells with different p53 mutation and hepatitis B virus infection status.

Results: Median follow-up and survival time in the TACE alone and TACE + radiotherapy groups were 39 and 19 months, and 51 and 17 months, respectively. Additional radiotherapy to TACE did not improve overall survival (P = 0.65). However, different failure patterns were noted after TACE and after radiotherapy. Although all irradiated tumors regressed substantially, radiotherapy rapidly enhanced both intrahepatic and extrahepatic tumor progression outside the radiotherapy treatment field in a significant portion of patients, which offset the benefit of radiotherapy on overall survival. In molecular analysis of the radiation effects on human hepatoma cells, radiotherapy rapidly induced p53-independent transcriptional up-regulation of vascular endothelial growth factor (VEGF), increased VEGF secretion in a dose-, time-, and cell type–dependent manner, and promoted hepatoma cell growth in vivo with enhanced intratumor angiogenesis, which correlated well with elevated levels of serum VEGF.

Conclusions: Radiotherapy to eradicate a primary hepatocellular carcinoma might result in the outgrowth of previously dormant microtumors not included in the radiotherapy treatment field. Radiotherapy-induced VEGF could be a paracrine proliferative stimulus. Therapeutic implications of the study justify the combination of three-dimensional conformal radiotherapy with anti-VEGF angiogenic modalities for the treatment of unresectable hepatocellular carcinoma to reduce relapses.
A Disaccharide-Based Inhibitor of Glycosylation Attenuates Metastatic Tumor Cell Dissemination
Authors: Brown Jillian R. , Fuster Mark M. , Li Ruixia , Varki Nissi , Glass Charles A. , Esko Jeffrey D.
Published: May 2006

Purpose: The binding of hematogenously borne malignant cells that express the carbohydrate sialyl Lewis X (sLeX) to selectin adhesion receptors on leukocytes, platelets, and endothelial cells facilitates metastasis. The glycosylation inhibitor, per-O-acetylated GlcNAcβ1,3Galβ-O-naphthalenemethanol (AcGnG-NM), inhibits the biosynthesis of sLeX in tumor cells. To evaluate the efficacy of AcGnG-NM as an antimetastatic agent, we examined its effect on experimental metastasis and on spontaneous hematogenous dissemination of murine Lewis lung carcinoma and B16BL6 melanoma cells.

Experimental Design: Tumor cells were treated in vitro with AcGnG-NM, and the degree of selectin ligand inhibition and experimental metastasis was analyzed in wild-type and P-selectin-deficient mice. Conditions were developed for systemic administration of AcGnG-NM, and the presence of tumor cells in the lungs was assessed using bromodeoxyuridine labeling in vivo. The effect of AcGnG-NM on inflammation was examined using an acute peritonitis model.

Results: In vitro treatment of Lewis lung carcinoma cells with AcGnG-NM reduced expression of sLeX- and P-selectin-dependent cell adhesion to plates coated with P-selectin. Treatment also reduced formation of lung foci when cells were injected into syngeneic mice. Systemic administration of the disaccharide significantly inhibited spontaneous dissemination of the cells to the lungs from a primary s.c. tumor, whereas an acetylated disaccharide not related to sLeX in structure had no effect. AcGnG-NM did not alter the level of circulating leukocytes or platelets, the expression of P-selectin ligands on neutrophils, or sLeX-dependent inflammation.

Conclusion: Taken together, these data show that AcGnG-NM provides a targeted glycoside-based therapy for the treatment of hematogenous dissemination of tumor cells.
Positioning Heaven: The Infidelity of a Faithful Aristotelian
Authors: McGinnis Jon
Published: May 2006

Aristotle's account of place in terms of an innermost limit of a containing body was to generate serious discussion and controversy among Aristotle's later commentators, especially when it was applied to the cosmos as a whole. The problem was that since there is nothing outside of the cosmos that could contain it, the cosmos apparently could not have a place according to Aristotle's definition; however, if the cosmos does not have a place, then it is not clear that it could move, but it was thought to move, namely, in its daily revolution, which was viewed as a kind of natural locomotion and so required the cosmos to have a place. The study briefly outlines Aristotle's account of place and then considers its fate, particularly with respect to the cosmos and its motion, at the hands of later commentators. To this end, it begins with Theophrastus' puzzles concerning Aristotle's account of place, and how later Greek commentators, such as Alexander of Aphrodisias, Themistius and others, attempted to address these problems in what can only be described as ad hoc ways. It then considers Philoponus' exploitation of these problems as a means to replace Aristotle's account of place with his own account of place understood in terms of extension. The study concludes with the Arabic Neoplatonizing Aristotelian Avicenna and his novel introduction of a new category of motion, namely, motion in the category of position. Briefly, Avicenna denies that the cosmos has a place, and so claims that it moves not with respect to place, but with respect to position.
The Suitability of US Security Laws and Regulations to serve as a Model Law for Egyptian Financial Markets
Authors: Zohny
Published: May 2006

No Abstract
Sponsors in Saudi Arabia: Myths and Realities
Authors:   Wapler
Published: May 2006

No Abstract
Trends in Satellite-Observed Circumpolar Photosynthetic Activity from 1982 to 2003: The Influence of Seasonality, Cover Type, and Vegetation Density
Authors: Bunn Andrew G. , Goetz Scott J.
Published: May 2006

Time series analyses of a 22-yr record of satellite observations across the northern circumpolar high latitudes were conducted, and trends in vegetation photosynthetic activity were assessed using a series of statistical tests. The results indicate that most of the northern circumpolar high latitudes (>85%) showed no significant trend in vegetation activity despite systematic climate warming during the period of analysis. Of the areas that did change, many showed the expected trends in “greening” of vegetation activity. There were, however, significant differences in the magnitude and even in the direction of trends when stratified by vegetation type and density. Tundra areas consistently and predominantly showed greening trends. Forested areas showed declines in activity (“browning”) in many areas, and these were systematically higher in areas with denser tree cover—whether deciduous or evergreen, needle- or broad-leafed. The seasonality of the trends was also distinct between vegetation types, with a divergence in trends between late spring and early summer (positive) versus late summer (negative) portions of the growing seasons in forested areas. In contrast, tundra and other predominantly herbaceous areas showed positive trends in all portions of the growing season. These results confirm recent findings across the high latitudes of North America and are supported by an increasing array of in situ measurements. They indicate that the boreal forest biome might be responding to climate change in previously unexpected ways, and point to a need for an expanded observational network, additional analysis of existing datasets (e.g., tree rings), and improvements in process models of ecosystem responses to climate change.
Public Opinion and the Governance of Punishment in Democratic Political Systems
Authors: Zimring Franklin E. , Johnson David T.
Published: May 2006

It is unlikely that hostile attitudes about criminals or beliefs that punishments for crime were too lenient were the major causes of the explosive increase in punishments in the United States after 1970. Public hostility toward criminals has been a consistent theme in this country for a long time, but it did not cause big increases in imprisonment before 1970 in the United States or large expansions of incarceration elsewhere. In this article, the authors argue that growth in the salience of crime as a citizen concern and increasing public distrust of government competence and legitimacy were two of a number of changes that transformed ever-present hostile attitudes into a dynamic force in American politics. Negative attitudes toward offenders are a necessary condition for anticrime crusades, but they are always present. It was the addition of fear and distrust into the law and politics of punishment setting that produced the perfect storm of punitive expansion.
Policing, Recognition, and Belonging
Authors: Loader Ian
Published: May 2006

In this article, the author reflects on the question of how policing institutions can help to foster and sustain the values and practices of democracy. The author’s overarching concern is to outline and defend a conception of democratic policing that highlights the role of policing agencies in recognizing the legitimate claims of all individuals and groups affected by police actions and affirming their sense of belonging to a political community. From this perspective, the author offers a critique of certain prominent forms of what he calls “ambient policing” and aims to cast some new light on the issue of how policing contributes to—or undermines—citizen security in democratic societies.
Democratization and Political Change as Threats to Collective Sentiments: Testing Durkheim in Russia
Authors: Pridemore William Alex , Kim Sang-Weon
Published: May 2006

Durkheim argued that acute political crises result in increased homicide rates because they pose a threat to sentiments about the collective. Though crucial to Durkheim’s work on homicide, this idea remains untested. The authors took advantage of the natural experiment of the collapse of the Soviet Union to examine this hypothesis. Using data from Russian regions ( N = 78) and controlling for measures of anomie and other covariates, the authors estimated the association between political change and change in homicide rates between 1991 and 2000. Results indicated that regions exhibiting less support for the Communist Party in 2000 (and thus greater change in political ideals because the Party had previously exercised complete control) were regions with greater increases in homicide rates. Thus, while democratization may be a positive development relative to the Communist juggernaut of the past, it appears that the swift political change in Russia is partially responsible for the higher rates of violence there following the collapse of the Soviet Union.
Policing Uncertainty: Countering Terror through Community Intelligence and Democratic Policing
Authors: Innes Martin
Published: May 2006

This article explores how counterterrorism policing strategies and practices in the United Kingdom have changed in the face of recent terrorist attacks. It considers the evident limitations of these developments and how a local, democratic style of neighborhood policing could be used to manufacture the community intelligence “feed” that offers the best probability of preventing and deterring future forms of such violence. These substantive concerns are set against a theoretical backdrop attending to how policing can respond to risks where the contours of the threat are uncertain. The analysis is informed by interviews with U.K. police officers involved in intelligence and counterterrorism work conducted during the early part of 2005.
The Right to Unionize, the Right to Bargain, and the Right to Democratic Policing
Authors: Marks Monique , Fleming Jenny
Published: May 2006

This (normative) article explores the importance of police unions in the quest for democratic policing. The authors argue that if we are to expect police to behave democratically, it is important for police themselves to experience democratic engagement within the organizations in which they work. That is, if police are expected to defend democracy, they should not be denied basic democratic rights such as the right to collective bargaining and the right to freedom of association. The authors contend that police unions, through networking with other social justice groupings and through encouraging democratic practice, constitute a real forum for the promotion of democratic policing. For this potential to be reached, however, police unions need to identify with broader labor movement trends toward community unionism.
Democracy and Criminal Justice in Cross-National Perspective: From Crime Control to Due Process
Authors: Sung Hung-En
Published: May 2006

In this article, the author argues that the transformation of justice administration in democratizing countries is a transition from a crime control to a due process orientation. In authoritarian states, criminal justice systems rely on a larger law enforcement-punishment apparatus for order maintenance and produce higher rates of arrest, prosecution, conviction, and incarceration. By contrast, in liberal democracies, justice is sought as the defense of civil liberties through the due process of law, which leads to a heavier investment in the judiciary and a higher rate of case attrition in the criminal justice process. The analysis of United Nations data refutes the hypothesis of larger police and prison workforce in authoritarian countries and larger judicial staff in liberal democracies. Instead, democracy increases both the personnel strength of the courts and that of the police and the prisons. The proposed relationship between democracy and increased criminal case attrition receives very strong support.