bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrocyclic Statine‐Based Inhibitors of BACE‐1
Authors: Barazza Alessandra , Götz Marion , Cadamuro Sergio A. , Goettig Peter , Willem Michael , Steuber Holger , Kohler Tanja , Jestel Anja , Reinemer Peter , Renner Christian , Bode Wolfram , Moroder Luis 
Published: October 2007

AbstractMinimal sequence requirements for binding of substrate‐derived statine peptides to the aspartyl enzyme were established on the basis of the X‐ray cocrystal structure of the hydroxyethylene‐octapeptide OM00‐3 in complexation with BACE‐1. With this information to hand, macrocyclic compounds that conformationally restrict and preorganize the peptide backbone for an entropically favoured binding to the enzyme active site cleft were designed. By means of a side chain‐to‐side chain ring closure between two aspartyl residues in the P2 and P3′ positions through phenylene‐1,3‐dimethanamine, a 23‐membered ring structure was obtained; this structure retained an extended conformation of the peptide backbone, including the transition state analogue statine for tight interactions with the two aspartyl residues of the active centre. The conformational preorganization of the inhibitor molecule was verified by NMR structural analysis and was then confirmed by the crystal structure of the BACE‐1/inhibitor complex. Detailed insights into the binding mode of this macrocyclic inhibitor explained its moderate binding affinity in cell‐free assays (Ki=2.5 μM) and yielded precious information for possible structural optimization in view of the lack of steric clashes of the macrocycle with the flap domain of the enzyme.
Desorption and Biofiltration for the Treatment of Residual Organic Gases Evolved in Soil Decontamination Processses
Authors: Barona A. , Elías A. , Arias R. , Acha E. , Cano I. 
Published: October 2007

AbstractIn order to analyze the combination of a rotary kiln and a biofilter in soil decontamination processes, a previously characterized soil was artificially contaminated with toluene, ethylbenzene or p‐xylene. The desorption peak of the three compounds occurred very quickly at 20 °C, and consequently, the outlet gas flow from the rotary kiln was initially divided into two different flows. One of them was reduced to a 1/9th fraction of the total flow to be treated in an independent biofiltration system specially acclimated to each contaminant. The sharp desorption peak observed for the three compounds at the outlet of the kiln involved a very high inlet concentration fed into the biofilters in a very short period of time (shorter than 3 h). Consequently, the removal efficiency for toluene was lower than 70 %. However, the removal efficiencies for ethylbenzene and xylene were always higher than 65 %.
Mathematical Modeling of the Fluidized Bed Drying of Cubic Materials
Authors: Hatamipour M. S. , Jazini M. H. 
Published: October 2007

AbstractThe unsteady‐state simultaneous heat and mass transfer between gas and potato cubes during the drying process in a batch fluidized bed was described by a mathematical model. Mass transfer was considered to occur in three dimensions whereas heat transfer between the gas and dried material was assumed to be lumped. It was found that the model could describe the drying process with acceptable accuracy. The moisture profile inside the material at any cross‐section and at any time can be predicted by the model.
Ammonium, Alkylammonium, and Amino Acid Complexes of a Hexacopper Fluoro‐Metallacrown Cavitand
Authors: Jones Leigh F. , Barrett Simon A. , Kilner Colin A. , Halcrow Malcolm A. 
Published: October 2007

AbstractReaction of CuF2 with one equivalent of 3{5}‐(pyrid‐2‐yl)‐5{3}‐(tertbutyl)pyrazole (HL) and excess NH4OH in MeOH affords crystalline [NH4{Cu(μ‐F)(μ‐L)}6(CH2Cl2)2]HF2 in moderate yield. This compound contains the 12‐MC‐6 metallacrown [{Cu(μ‐F)(μ‐L)}6] (1) with a NH4+ ion at its center, and CH2Cl2 molecules complexed in bowl‐shaped cavities above and below the Cu6F6 ring. Similar reactions using the bases MeNH2, glycine, l‐alanine or β‐alanine afforded solvated crystals of [1(H3NMe)2]Cl2, [1(gly)2], [1(l‐ala)2], and [1(β‐ala)2], respectively. The metallacrown 1 in these products contains methylammonium and zwitterionic amino‐acid guests in its two bowl‐shaped cavities; each of the amino acids hydrogen‐bonds to three F atoms. A related reaction using 1,6‐diaminohexane resulted in fixation of CO2 from the air to give solvated [1(H3NC6H12NHCO2)2], again with a zwitterionic guest. NMR, ESI‐MS and UV/vis measurements suggest that the metallacrown 1 retains its integrity in several organic solvents, although it is unclear to what extent guest binding takes place in solution.
Prodrug Strategies in Anticancer Chemotherapy
Authors: Kratz Felix , Müller Ivonne A. , Ryppa Claudia , Warnecke André 
Published: October 2007

AbstractThe majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor‐specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor‐specific characteristics such as low pH or the expression of tumor‐associated enzymes. Furthermore, other strategies such as ADEPT (antibody‐directed enzyme prodrug therapy) and the design of self‐eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.
Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA‐87 and LALA‐94 trials
Authors: Tavernier Emmanuelle , Le Quoc‐Hung , de Botton Stéphane , Dhédin Nathalie , Bulabois Claude‐Eric , Reman Oumedaly , Vey Norbert , Lhéritier Véronique , Dombret Hervé , Thomas Xavier 
Published: October 2007

AbstractBACKGROUND.Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). Although treatment intensity and outcome were not comparable, with improvements in survival it is important to evaluate the rate and the type of second neoplasms in adults with ALL.METHODS.The data from the GET‐LALA group were analyzed. A cohort of 1494 patients, aged 15 to 60 years and enrolled in 2 successive multicenter protocols between 1987 and 2002, was observed to determine the incidence of second neoplasms and associated risk factors. The median follow‐up from diagnosis was 6 years.RESULTS.By February 2005 secondary or concomitant neoplasms were documented in 23 patients, including 9 acute myeloid leukemias (AML) or myelodysplasias (MDS), 4 non‐Hodgkin lymphomas (NHL), 5 skin tumors, and 5 other solid tumors (1 lung cancer, 1 tongue carcinoma, 1 thymoma, 1 condrosarcoma, 1 histiocytosis). Neoplasms developed 0.5 to 13.8 years (median, 4.5 years) after the diagnosis of ALL. There were 22 patients in first remission and 1 was in second remission. The overall cumulative risk of secondary neoplasms was 2.1% at 5 years, 4.9% at 10 years, and 9.4% at 15 years. The cumulative risk of developing a second hematologic malignancy was 1.8% at 5 years, 2.2% at 10 years, 3.3% at 18 years; that of developing a solid tumor was 0.2% at 5 years, 2.8% at 10 years, 6.2% at 15 years. The development of secondary neoplasm was not associated with the use of any specific cytotoxic agent. However, the risk of skin tumor increased with radiation dose and transplantation (P = .01). Overall survival (OS) after the diagnosis of a second malignant neoplasm was 55% at 10 years. However, the median OS in patients developing AML/MDS was 5.7 months.CONCLUSIONS.The data document that adult ALL survivors are at an increased risk of later malignancy. The risk of secondary or concomitant neoplasm appeared higher than that of childhood ALL previously reported in the literature. Considering the low survival rate of this large unselected adult ALL cohort (32% at 10 years) as compared with that observed in childhood ALL, the risk of second malignancy remains underestimated. Larger series with long‐term follow‐up are necessary, as well as methods of screening and identification of patients at increased risk. Cancer 2007. © 2007 American Cancer Society.
Conflict resolution education and antisocial behavior in U.S. schools: A meta‐analysis
Authors: Garrard Wendy M. , Lipsey Mark W. 
Published: October 2007

AbstractThis meta‐analysis examines more than twenty‐five years of evidence to determine whether participation in school‐based conflict resolution education (CRE) contributes to reduced antisocial behaviors among youth in kindergarten through twelfth grade in U.S. schools. Evidence from thirty‐six studies, representing 4,971 students, shows improvements in antisocial behaviors in CRE participants compared to control groups (Effect Size = .26), with larger effects observed during midadolescence ( ES = .53) and early adolescence ( ES = .22) compared to middle childhood ( ES = .06). Improvements in antisocial behavior outcomes attributable to CRE are significant in both practical and statistical terms and are similar for different CRE program approaches.
Novel therapeutics with enhanced biological activity generated by the strategic introduction of silicon isosteres into known drug scaffolds
Authors: Gately Stephen , West Robert 
Published: October 2007

AbstractThe strategic replacement of carbon with silicon within biologically prevalidated drug scaffolds can generate focused libraries of pharmaceutically relevant agents with novel, durable and marketable intellectual property. This approach can be cost‐effective and of lower developmental risk because known drugs have recognized pharmacology and toxicity profiles, proven safety in humans, and established manufacturing and formulation methods. The change in shape, charge, and lipophilicity that can result from the addition of silicon can favorably alter the biological activity and toxicology of the parent drug. Silicon‐containing derivatives of indomethacin are COX‐2 selective, suggesting they will not be associated with the classical toxicities associated with nonselective inhibition of the cyclooxygenases. The silicon‐indomethacin derivatives also demonstrated superior anti‐cancer activity at clinically achievable concentrations when tested in vitro against a human pancreatic cancer cell line, MiaPaCa‐2, and a panel of 14 human multiple myeloma cell lines. Bioorganosilicon chemistry represents an attractive approach for emerging biopharmaceutical organizations seeking to rapidly develop a portfolio of novel pharmacological agents that have the potential for enhanced therapeutic and pharmacological benefit. Drug Dev Res 68:156–163, 2007. ©2007 Wiley‐Liss, Inc.
UNBS1450: A new hemi‐synthetic cardenolide with promising anti‐cancer activity
Authors: Mijatovic Tatjana , Lefranc Florence , Van Quaquebeke Eric , Van Vynckt Frank , Darro Francis , Kiss Robert 
Published: October 2007

AbstractSeveral reports suggest the sodium pump as an interesting oncology target, given that its subunit expression is markedly altered in cancer. By binding to the sodium pump, cardiotonic steroids, notably cardenolides, the natural high‐affinity Na+/K+‐ATPase ligands, elicit marked effects on cancer cell behavior and a number of studies have emphasized their potential use in oncology. Chemical modifications of 2″‐oxovoruscharin (a novel cardenolide extracted from Calotropis procera) based on an understanding of the structure–activity relationship within the series, has led to the identification of UNBS1450, a molecule characterized by more potent anti‐proliferative activity and lower toxicity than classic cardenolides. In aggressive and metastatic orthotopic NSCLC, refractory prostate cancer, and glioma models, UNBS1450 is more potent than tested reference compounds, including taxol, irinotecan, oxaliplatin, mitoxantrone, and temozolomide. The general mechanism of action associated with UNBS1450‐mediated anti‐cancer effects relates to the disorganization of the actin cytoskeleton. UNBS1450 can thus be considered both anti‐proliferative (cytotoxic) and anti‐migratory, given that the actin cytoskeleton is essential to cytokinesis and to cancer cell migration. UNBS1450 also induces non‐apoptotic cell death processes (e.g., lysosome membrane permeabilization and autophagy) and thus may overcome major apoptosis resistance pathways responsible for the failure of therapeutics in certain cancers. UNBS1450 is currently in preclinical development and should reach Phase I clinical trials in 2008. Drug Dev Res 68:164–173, 2007. ©2007 Wiley‐Liss, Inc.
Building systems to support development of drugs for biodefense
Authors: Taylor Katherine A. 
Published: October 2007

AbstractThe mission of the National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID), is to support research and product development that addresses the control and prevention of infectious diseases. This mission includes the development of new drugs to mitigate illness, suffering, and death resulting from an expanding spectrum of naturally emerging diseases and potential biological weapons. DMID has established new resources and additional infrastructure to address these challenges. In addition, DMID plans to transition to a new paradigm for research and development approaches based on three concepts that comprise a broad spectrum approach: products with broad spectrum activity; broad spectrum technology that can be applied to improve specific drug characteristics (e.g., shelf life); and broad spectrum platforms that will reduce the time and cost to manufacture and evaluate products. Drug Dev Res 68:183–185, 2007. © 2007 Wiley‐Liss, Inc.
Nonprofit model for drug discovery and development
Authors: Frank Gregory Daniel , Jong Ling , Collins Nathan , Spack Edward G. 
Published: October 2007

AbstractSRI International, a nonendowed, nonprofit research institution, has developed a successful model for drug discovery and development using funding from a variety of sources. We have vertically integrated basic and applied research, drug discovery, and preclinical drug development expertise and capabilities. Funding sources include state and federal government grants and contracts, and our unique model allows us to translate our discoveries into clinical‐ready drug candidates. Drug Dev Res 68:186–196, 2007. © 2007 Wiley‐Liss, Inc.
Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise
Authors: Vu Vivian , Riddell Michael C. , Sweeney Gary 
Published: October 2007

AbstractExcess visceral fat can regulate insulin sensitivity and energy metabolism by releasing adipokines into the circulation which then bind with their cognate receptors in various tissues and alter glucose and lipid metabolism. Circulating levels of adiponectin, which promotes glucose uptake into skeletal muscle and increases fat oxidation rates, are decreased in obesity. Strategies to enhance the insulin‐like and insulin‐sensitizing actions of adiponectin have been shown to be effective in improving metabolic abnormalities associated with obesity and diabetes. Interestingly, the insulin‐sensitizing effects of exercise have similar metabolic effects as adiponectin in that exercise also promotes glucose uptake into muscle and increases rates of fatty acid oxidation. Recent studies have begun to examine the potential role of adiponectin in mediating the insulin‐sensitizing action of exercise by investigating changes in plasma adiponectin levels and tissue‐specific adiponectin receptor (AdipoR) expression. In this review, we have summarized the key findings to date which suggest that changes in expression of AdipoR isoforms in skeletal muscle, rather than circulating total adiponectin levels, may be of physiological importance. Copyright © 2007 John Wiley & Sons, Ltd.
The N‐Acylated Derivatives of Parent Complex [{(μ‐SCH2)2NH}Fe2(CO)6] as Active Site Models of Fe‐Only Hydrogenases: Synthesis, Characterization, and Related Properties
Authors: Song Li‐Cheng , Wang Liang‐Xing , Yin Bang‐Shao , Li Yu‐Long , Zhang Xiao‐Guang , Zhang Yuan‐Wei , Luo Xiang , Hu Qing‐Mei 
Published: October 2007

AbstractA series of N‐acylated diiron azadithiolate complexes as H‐cluster models was synthesized and structurally characterized. Treatment of parent complex [{(μ‐SCH2)2NH}Fe2(CO)6] (A) with 2‐chloroacetic acid in the presence of dicyclohexylcarbodiimide or with 2‐chloroacetyl chloride in the presence of Et3N gave N‐chloroacetyl complex [{(μ‐SCH2)2NC(O)CH2Cl}Fe2(CO)6] (1). Further treatment of 1 with MeC(O)SK afforded N‐acetylthioacetyl complex [{(μ‐SCH2)2NC(O)CH2SC(O)Me}Fe2(CO)6] (2). N‐Ethoxylcarbonylacetyl complex [{(μ‐SCH2)2NC(O)CH2CO2Et}Fe2(CO)6] (3) and N‐heterocyclic complexes [{(μ‐SCH2)2NC(O)C4H3Y‐2}Fe2(CO)6] (4, Y = O; 5, Y = S) were produced by reactions of A with EtO2CCH2C(O)Cl, 2‐furancarbonyl chloride, and 2‐thiophenecarbonyl chloride in the presence of pyridine or Et3N. Similarly, N‐malonyl complex [{Fe2(CO)6(μ‐SCH2)2NC(O)}2CH2] (6) and N‐carbonylbenzaldehyde complex [{(μ‐SCH2)2NC(O)C6H4CHO‐p}Fe2(CO)6] (7) could be obtained by reaction of A with malonyl dichloride in the presence of pyridine and with p‐CHOC6H4C(O)Cl in the presence of Et3N. More interestingly, further reaction of 7 with PhCHO and pyrrole in a 1:3:4 molar ratio in the presence of BF3·OEt2 followed by p‐chloranil yielded the first light‐driven type of model complex containing an N‐carbonylphenylporphyrin moiety [{(μ‐SCH2)2NC(O)(TPP)}Fe2(CO)6] (8, TPP = tetraphenylporphyrin group). Whereas the molecular structures of 2, 5, and 7 were established by X‐ray crystallography, the electrochemical properties of 2–5 as well as the proton reduction to hydrogen gas catalyzed by 2 and 3 were studied by CV techniques.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Tissue engineering with electric fields: Investigation of the shape of mammalian cell aggregates formed at interdigitated oppositely castellated electrodes
Authors: Sebastian Anil , Venkatesh Alagarswamy G. , Markx Gerard H. 
Published: October 2007

AbstractThe shape of aggregates of cells formed by positive dielectrophoresis (DEP) at interdigitated oppositely castellated electrodes under different conditions was investigated and compared with calculations of the electric field gradient |∇E2|, and the electric field E, and E2. The results confirm that at low field strength the cells predominantly accumulate above the tips of the electrodes, but at higher electric field strengths the cells predominantly accumulate in the middle of the aggregate. For a given electrode size, a higher applied voltage significantly increases the aggregate footprint. Higher flow rates distort this pattern, with more cells accumulating at the electrodes that are upstream. Calculation of the electric field strength E, E2 and the electric field strength gradient |∇E2| in the interdigitated oppositely castellated electrode array shows that, at low flow rates, there is a strong correlation between the aggregate shape and the distribution of the electric field E and E2, but not so between the aggregate shape and |∇E2|. The results indicate that interparticle forces such as pearlchain formation strongly affect the aggregation process, but that, when positive DEP is used to make the aggregates, the distribution of the electric field E, or better E2, can be used as a useful guide to the final aggregate shape.
Adaptive shifts in osmoregulatory strategy and the invasion of freshwater by brachyuran crabs: evidence from Dilocarcinus pagei (Trichodactylidae)
Authors: Augusto Alessandra , Greene Lewis J. , Laure Helen J. , Mcnamara John C. 
Published: October 2007

AbstractTo evaluate putative adaptive changes underpinning the invasion of freshwater by the Brachyura, this investigation examines anisosmotic extra and isosmotic intracellular osmoregulatory capabilities in Dilocarcinus pagei, a neotropical, hololimnetic crab, including its embryonic and juvenile phases. All ontogenetic stages show a remarkable ability to survive a high salinity medium (25‰, 750 mOsm/kg H2O, 350 mm Na+, 400 mM Cl−). Adults hyper‐regulate hemolymph osmolality up to isosmoticity at 744 mOsm kg/H2O (24‰), [Na+] and [Cl−] becoming isoionic at 449 (22‰) and 256 mM (16‰), respectively. Hemolymph (420±39 mOsm/kg H2O) and urine (384±44 mOsm/kg H2O) are isosmotic in adults held in freshwater, and after 5‐days exposure to 25‰ (787±9 mOsm/kg H2O and 777±43 mOs/kg H2O, respectively); D. pagei does not produce dilute urine. Total free amino acid (FAA) concentrations in embryos (14.9±1.2), juveniles (32.8±0.1) and adult muscle (10.9±2.1 mmol/kg wet weight) in freshwater are 30‐fold less than in brackish/marine Crustacea, suggesting that FAA constitute a useful parameter to evaluate adaptation to freshwater. On acclimation to 25‰, total FAA increase by ≈100% in embryos and in adult muscle and nerve tissue and hemolymph, owing to large increases in proline, arginine and/or alanine. However, effective FAA contribution to intracellular osmolality increases only in embryos, from 3 to 4.5%. These findings suggest that gill‐based, anisosmotic extracellular regulation has supplanted isosmotic intracellular regulatory mechanisms during the conquest of freshwater by the Brachyura, and indicate that D. pagei may be an old, well‐adapted inhabitant of this biotope. J. Exp. Zool. 307A:688–698, 2007. © 2007 Wiley‐Liss, Inc.
Inter‐decadal variation of the summer precipitation in East China and its association with decreasing Asian summer monsoon. Part I: Observed evidences
Authors: Ding Yihui , Wang Zunya , Sun Ying 
Published: October 2007

AbstractIn recent two decades, North and Northeast China have suffered from severe and persistent droughts while the Yangtze River basin and South China have undergone much more significant heavy rainfall/floods events. This long‐term change in the summer precipitation and associated large‐scale monsoon circulation features have been examined by using the new dataset of 740 surface stations for recent 54 years (1951–2004) and about 123‐yr (1880–2002) records of precipitation in East China. The following new findings have been highlighted: (1) One dominating mode of the inter‐decadal variability of the summer precipitation in China is the near‐80‐yr oscillation. Other modes of 12‐yr and 30–40‐yr oscillations also play an important role in affecting regional inter‐decadal variability. (2) In recent 54 years, the spatial pattern of the inter‐decadal variability of summer precipitation in China is mainly structured with two meridional modes: the dipole pattern and the positive‐negative‐positive (“+ − + ” pattern). In this period, a regime transition of meridional precipitation mode from “+ − + ” pattern to dipole pattern has been completed. In the process of southward movement of much precipitation zone, two abrupt climate changing points that occurred in 1978 and 1992, respectively, were identified. (3) Accompanying the afore‐described precipitation changes, the East Asian summer monsoon have experienced significant weakening, with northward moisture transport and convergence by the East Asian summer monsoon greatly weakened, thus leading to much deficient moisture supply for precipitation in North China. (4) The significant weakening of the component of the tropical upper‐level easterly jet (TEJ) has made a dominating contribution to the weakening of the Asian summer monsoon system. The cooling in the high troposphere at mid‐ and high latitudes and the possible warming at low latitude in the Asian region is likely to be responsible for the inter‐decadal weakening of the TEJ. Copyright © 2007 Royal Meteorological Society