bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ree and Sr-Nd Isotope Compositions of Clinopyroxenites, Phoscorites and Carbonatites of the Seblyavr Massif, Kola Peninsula, Russia
Authors: Balaganskaya Elena , Downes Hilary , Demaiffe Daniel 
Published: January 2008

Ree and Sr-Nd Isotope Compositions of Clinopyroxenites, Phoscorites and Carbonatites of the Seblyavr Massif, Kola Peninsula, RussiaClinopyroxenites, phoscorites and carbonatites from the Devonian Seblyavr intrusion (Kola Peninsula, Russia) have petrographic characteristics indicating that they are accumulative in origin. Their geochemical (major and rare earth elements) compositions can be accounted for by mixtures of their major rock-forming minerals and accessory phases, i.e. they reflect the record of mineral accumulation. All of the analysed Seblyavr rocks are strongly LREE-enriched with (La/Yb)Nmostly ranging from 38 to 189. However, a dolomite carbonatite with hydrothermal LREE-Sr mineralization has an extreme (La/Yb)Nvalue of 1659. Such late-stage dolomite carbonatites were formed by hydrothermal (rather than magmatic) processes. Whole-rock samples of representative magmatic lithologies from Seblyavr have initial87Sr/86Sr and εNdthat fall in a very narrow range from 0.7031 to 0.7033 and +4.9 to +5.9, respectively. We therefore conclude that clinopyroxenites, phoscorites and carbonatites were formed by differentiation and crystallization of a single batch of melt. The parental melt was derived from a depleted upper mantle source that had been meta-somatised prior to melting.
Das ideale Plentergleichgewicht – Leitbild oder Luxus? (Essay) | The ideal equilibrium state in a selection forest – vision or luxury? (essay)
Authors: Sonnemann Dana 
Published: January 2008

In managing unevenly aged forests, conventional ideal equilibrium models based on curves of declining stem numbers have relied on the overall concept of a simultaneous fulfilment of various aims. The study presented here investigated whether such models are adaptable to current economic conditions and to what extent financial objectives could be optimized without infringing on structural requirements.
A linear, time discrete equilibrium model calibrated with data collected from a sample area within a Swiss selection forest was combined with a linear optimization model. Financial objectives were optimized in numeric experiments under a range of strictness values for stand-structure constraints. The results were compared with those obtained from an exemplary conservative ideal model. This evaluation found system equilibria far from that reference, and it also found some wich could generate a much higher income. However, the most meaningful increase of the target variable could be realized without requiring any critical deviation from the compared model. This could be accomplished by augmenting the current growing stock while reducing the maximum diameter at breast height. Therefore, management interventions that incur losses could be abandoned in the lower diameter classes, and only trees above a specified diameter would then be harvested. In applying this new model, the decision makers would be asked to thoroughly analyze their management objectives and the given restrictions on acting accordingly. Hence, they could immediately provide arguments to justify their decisions.
Evaluation of large Eddy simulation and Euler‐Euler CFD models for solids flow dynamics in a stirred tank reactor
Authors: Guha Debangshu , Ramachandran P. A. , Dudukovic M. P. , Derksen J. J. 
Published: January 2008

AbstractMechanically agitated reactors find wide range of applications for solid suspension and mixing in the chemical, biochemical, and mineral processing industries. Understanding the solids dynamics in these reactors is necessary to improve the design and operation of such reactors. Computational fluid dynamic (CFD) models are often useful in this regard, as it can provide significant insights into the flow and mixing of the phases involved. However, the model predictions need extensive evaluation with experimental results before they can be confidently used for the scale‐up and optimization of large scale reactors. Recently, Guha et al. carried out a systematic experimental investigation of the solids hydrodynamics in dense solid–liquid suspensions (2.5–19% solids loading w/w) in a stirred tank using the Computer Automated Radioactive Particle Tracking (CARPT) technique, which provided extensive information to efficiently assess the ability of the existing CFD models in predicting the solids dynamics in slurry reactors. This work presents such an evaluation by comparing the averaged solids velocities, turbulent kinetic energy, and solids sojourn time distributions predicted by CFD models with those obtained from the CARPT experiment for overall solids holdup of 1% (v/v) (2.5% w/w) at Reynolds number of 74,000. The Large Eddy Simulation (LES) and the Euler‐Euler model are the models chosen for evaluation in the current study. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Rheology of a low‐filled polyamide 6/montmorillonite nanocomposite
Authors: Xu Guangyang , Chen Guangming , Ma Yongmei , Ke Yucai , Han Minfang 
Published: January 2008

AbstractThe rheological properties of a polyamide 6/clay nanocomposite with a low loading of clay (1 wt %) were studied. Linear viscoelastic measurements in oscillatory and steady shear with small strain amplitudes were carried out. The nanocomposite exhibited a higher elastic modulus, viscous modulus, and complex viscosity than neat polyamide 6 during dynamic and steady shear tests. Moreover, the addition of clay resulted in a reduction of the critical strain amplitude, an increase of the loss angle, and a reduction of the frequency at the intersection of the elastic and viscous moduli. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci 2008
Halide Anion Mediated Dimerization of a meso‐Unsubstituted N‐Confused Porphyrin
Authors: Furuta Hiroyuki , Nanami Hideki , Morimoto Tatsuki , Ogawa Takuji , Král Vladimir , Sessler Jonathan L. , Lynch Vincent 
Published: January 2008

AbstractThe new N‐confused porphyrin (NCP) derivatives, meso‐unsubstituted β‐alkyl‐3‐oxo N‐confused porphyrin (3‐oxo‐NCP) and related macrocycles, were synthesized from appropriate pyrrolic precursors by a [3+1]‐type condensation reaction. 3‐Oxo‐NCP forms a self‐assembled dimer in dichloromethane that is stabilized by complementary hydrogen‐bonding interactions arising from the peripheral amide‐like moieties. The protonated form of 3‐oxo‐NCP was observed to bind halide anions (F−, Cl−) through the outer NH and the inner pyrrolic NH groups, thus affording a dimer in dichloromethane. The structure of the chloride‐bridged dimer in the solid state was determined by X‐ray diffraction analysis.
Variables in right iliac fossa anatomy and their relevance to appendicectomy: Improving knowledge and practices
Authors: Hegde Devdas , Hegde Sachin Dev 
Published: January 2008

AbstractThe anatomy of the right iliac fossa was reappraised with the intention of improving, open appendicectomy. The surface anatomy was studied on volunteers and the internal topography was examined during the operation of appendicectomy. Our findings vary slightly from prevailing knowledge which is mostly based on cadaver anatomy. Our findings suggest that McBurney's point is very close to the rectus sheath in some individuals and in most subjects it does not overly base of appendix. Surgical teaching through most of the 20th century stressed safety and recommended large incisions with generous exposure, allowing surgeons to operate yet not appreciate these variables. An attempt is made to provide a precise account of the variables in right iliac fossa anatomy to help surgeons operate using smaller, minimally invasive incisions with the inevitable reduced exposure of local anatomy. The proximity of the base of the appendix to the ileocaecal junction raises concern that burial of the appendicular stump might distort local anatomy. Clin. Anat. 21:165–170, 2008. © 2008 Wiley‐Liss, Inc.
Rational Protein Design of ThDP‐Dependent Enzymes—Engineering Stereoselectivity
Authors: Gocke Dörte , Walter Lydia , Gauchenova Ekaterina , Kolter Geraldine , Knoll Michael , Berthold Catrine L. , Schneider Gunter , Pleiss Jürgen , Müller Michael , Pohl Martina 
Published: January 2008

AbstractBenzoylformate decarboxylase (BFD) from Pseudomonas putida is an exceptional thiamin diphosphate‐dependent enzyme, as it catalyzes the formation of (S)‐2‐hydroxy‐1‐phenylpropan‐1‐one from benzaldehyde and acetaldehyde. This is the only currently known S‐selective reaction (92 % ee) catalyzed by this otherwise R‐selective class of enzymes. Here we describe the molecular basis of the introduction of S selectivity into ThDP‐dependent decarboxylases. By shaping the active site of BFD through the use of rational protein design, structural analysis, and molecular modeling, optimal steric stabilization of the acceptor aldehyde in a structural element called the S pocket was identified as the predominant interaction for adjusting stereoselectivity. Our studies revealed Leu461 as a hot spot for stereoselectivity in BFD. Exchange to alanine and glycine resulted in variants that catalyze the S‐stereoselective addition of larger acceptor aldehydes, such as propanal with benzaldehyde and its derivatives—a reaction not catalyzed by the wild‐type enzyme. Crystal structure analysis of the variant BFDL461A supports the modeling studies.
Glycosylated Derivatives of Steffimycin: Insights into the Role of the Sugar Moieties for the Biological Activity
Authors: Olano Carlos , Abdelfattah Mohamed S. , Gullón Sonia , Braña Alfredo F. , Rohr Jürgen , Méndez Carmen , Salas José A. 
Published: January 2008

AbstractExpression of the steffimycin gene cluster in Steptomyces albus in combination with plasmids directing the biosynthesis of different neutral and branched‐chain deoxyhexoses led to the identification of twelve new glycosylated derivatives of steffimycin with different degrees of decoration in the tetracyclic core. These experiments demonstrate the flexibility of L‐rhamnosyltransferase StfG for recognition of a variety of D‐ and L‐deoxyhexoses, harboring different degrees of deoxygenation as 2‐deoxyhexoses, 2,6‐deoxyhexoses, and 2,3,6‐deoxyhexoses, and their attachment to 8‐demethoxy‐10‐deoxysteffimycinone. In addition, the flexibility of 3′‐O‐methyltransferase OleY, from Streptomyces, for the methylation of deoxyhexoses attached to the steffimycin aglycone is shown by expression of oleY in Streptomyces steffisburgensis, leading to the isolation of 3′‐O‐methylsteffimycin. Analysis of the biological activities of these compounds against three human tumor cell lines—breast adenocarcinoma, non‐small cell lung cancer, and colon adenocarcinoma—revealed two of them, 3′‐O‐methylsteffimycin and D‐digitoxosyl‐8‐demethoxy‐10‐deoxysteffimycinone, to possess improved antitumor activities, showing GI50 values below 1.0 μM, while steffimycin’s GI50 values fluctuate between 2.61 to 6.79 μM depending upon the cell line used. The antitumor activity data provide some insights into the structure–activity relationships of the new steffimycin derivatives, in relation to the configuration of hydroxy groups at positions C‐3′ and C‐4′ of the sugar moiety and positions C‐8 and C‐10 of the tetracyclic core.
Templated Synthesis of Electroactive Periodic Mesoporous Organosilica Bridged with Oligoaniline
Authors: Guo Yi , Mylonakis Andreas , Zhang Zongtao , Yang Guoliang , Lelkes Peter I. , Che Shunai , Lu Qinghua , Wei Yen 
Published: January 2008

AbstractThe synthesis and characterization of novel electroactive periodic mesoporous organosilica (PMO) are reported. The silsesquioxane precursor, N,N′‐bis(4′‐(3‐triethoxysilylpropylureido)phenyl)‐1,4‐quinonene‐diimine (TSUPQD), was prepared from the emeraldine base of amino‐capped aniline trimer (EBAT) using a one‐step coupling reaction and was used as an organic silicon source in the co‐condensation with tetraethyl orthosilicate (TEOS) in proper ratios. By means of a hydrothermal sol–gel approach with the cationic surfactant cetyltrimethyl‐ammonium bromide (CTAB) as the structure‐directing template and acetone as the co‐solvent for the dissolution of TSUPQD, a series of novel MCM‐41 type siliceous materials (TSU‐PMOs) were successfully prepared under mild alkaline conditions. The resultant mesoporous organosilica were characterized by Fourier transform infrared (FT‐IR) spectroscopy, thermogravimetry, X‐ray diffraction, nitrogen sorption, and transmission electron microscopy (TEM) and showed that this series of TSU‐PMOs exhibited hexagonally patterned mesostructures with pore diameters of 2.1–2.8 nm. Although the structural regularity and pore parameters gradually deteriorated with increasing loading of organic bridges, the electrochemical behavior of TSU‐PMOs monitored by cyclic voltammetry demonstrated greater electroactivities for samples with higher concentration of the incorporated TSU units.
Pd‐Catalyzed Aryl Amination Mediated by Well Defined, N‐Heterocyclic Carbene (NHC)–Pd Precatalysts, PEPPSI
Authors: Organ Michael G. , Abdel‐Hadi Mirvat , Avola Stephanie , Dubovyk Igor , Hadei Niloufar , Kantchev Eric Assen B. , O'Brien Christopher J. , Sayah Mahmoud , Valente Cory 
Published: January 2008

AbstractPd–N‐heterocyclic carbene (NHC)‐catalyzed Buchwald–Hartwig amination protocols mediated by Pd–PEPPSI precatalysts is described. These protocols provide access to a range of hindered and functionalized drug‐like aryl amines in high yield with both electron‐deficient and electron‐rich aryl‐ and heteroaryl chlorides and bromides. Variations in solvent polarity, base and temperature are tolerated, enhancing the scope and utility of this protocol. A mechanistic rationalization for base strength (pKb) requirements is also provided.
A Radical‐Anion Chain Mechanism Initiated by Dissociative Electron Transfer to a Bicyclic Endoperoxide: Insight into the Fragmentation Chemistry of Neutral Biradicals and Distonic Radical Anions
Authors: Magri David C. , Workentin Mark S. 
Published: January 2008

AbstractThe electron‐transfer (ET) reduction of two diphenyl‐substituted bicyclic endoperoxides was studied in N,N‐dimethylformamide by heterogeneous electrochemical techniques. The study provides insight into the structural parameters that affect the reduction mechanism of the OO bond and dictate the reactivity of distonic radical anions, in addition to evaluating previously unknown thermochemical parameters. Notably, the standard reduction potentials and the bond dissociation energies (BDEs) were evaluated to be −0.55±0.15 V and 20±3 kcal mol−1, respectively, the last representing some of the lowest BDEs ever reported. The endoperoxides react by concerted dissociative electron transfer (DET) reduction of the OO bond yielding a distonic radical‐anion intermediate. The reduction of 1,4‐diphenyl‐2,3‐dioxabicyclo[2.2.2]oct‐5‐ene (1) results in the quantitative formation of 1,4‐diphenylcyclohex‐2‐ene‐cis‐1,4‐diol by an overall two‐electron mechanism. In contrast, ET to 1,4‐diphenyl‐2,3‐dioxabicyclo[2.2.2]octane (2) yields 1,4‐diphenylcyclohexane‐cis‐1,4‐diol as the major product; however, in competition with the second ET from the electrode, the distonic radical anion undergoes a β‐scission fragmentation yielding 1,4‐diphenyl‐1,4‐butanedione radical anion and ethylene in a mechanism involving less than one electron. These observations are rationalized by an unprecedented catalytic radical‐anion chain mechanism, the first ever reported for a bicyclic endoperoxide. The product ratios and the efficiency of the catalytic mechanism are dependent on the electrode potential and the concentration of weak non‐nucleophilic acid. A thermochemical cycle for calculating the driving force for β‐scission fragmentation is presented, and provides insight into why the fragmentation chemistry of distonic radical anions is different from analogous neutral biradicals.
Modeling hERG and its Interactions with Drugs: Recent Advances in Light of Current Potassium Channel Simulations
Authors: Recanatini Maurizio , Cavalli Andrea , Masetti Matteo 
Published: January 2008

AbstractThe hERG K+ channel is responsible for the rapid delayed rectifier current in cardiac myocytes, and a block of its functioning may be related with the (inherited or drug‐induced) long QT syndrome. For this reason, in recent times, some interest has arisen around computational studies aimed at developing hERG/drug models for the prediction of drug binding (docking) modes, in view of the assessment of the hERG blocking potential. On the other hand, voltage‐gated K+ channels have been the subject of molecular simulations for several years, and rigorous protocols for studying the main aspects of their functions (permeation, gating, voltage sensing) have been published. In this article, we briefly introduce these classical computational works on K+ channels, and then review in depth the reports on the latest advanced modeling studies on hERG. The aim is to put the hERG modeling work in the more general context of the ion channel simulations field, to show the peculiarity of hERG on the one side, and also to indicate some possible new avenues in the use of modeling techniques to increase our knowledge of this important channel.
A 3D QSAR Model of 17β‐HSD1 Inhibitors Based on a Thieno[2,3‐d]pyrimidin‐4(3H)‐one Core Applying Molecular Dynamics Simulations and Ligand–Protein Docking
Authors: Karkola Sampo , Lilienkampf Annamaria , Wähälä Kristiina 
Published: January 2008

AbstractThe 17β‐hydroxysteroid dehydrogenase type 1 (17β‐HSD1) enzyme plays a crucial role in female hormonal regulation by catalysing the NADPH‐dependent reduction of the less potent estrone E1 into the biologically active estradiol E2. Because 17β‐HSD1 is a key enzyme in E2 biosynthesis, it has emerged as an attractive drug target for inhibitor development. Herein we report the plausible binding modes and a 3D QSAR model of 17β‐HSD1 inhibitors based on a (di)cycloalkenothieno[2,3‐d]pyrimidin‐4(3H)‐one core. Two generated enzyme complexes with potent inhibitors were subjected to molecular dynamics simulation to mimic the dynamic process of inhibitor binding. A set of 17β‐HSD1 inhibitors based on the thieno[2,3‐d]pyrimidin‐4(3H)‐one core were docked into the resulting active site, and a CoMFA model employing the most extensive training set to date was generated. The model was validated with an external test set. Active site residues involved in inhibitor binding and CoMFA fields for steric and electrostatic interactions were identified. The model will be used to guide structural modifications of 17β‐HSD1 inhibitors based on a thieno[2,3‐d]pyrimidin‐4(3H)‐one core in order to improve the biological activity as well as in the design of novel 17β‐HSD1 inhibitors.
Phase 1/2 trial of BMS‐275291 in patients with human immunodeficiency virus‐related Kaposi sarcoma
Authors: Brinker Brett T. , Krown Susan E. , Lee Jeannette Y. , Cesarman Ethel , Chadburn Amy , Kaplan Lawrence D. , Henry David H. , Von Roenn Jamie H. 
Published: January 2008

AbstractBACKGROUND.Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS‐275291, was evaluated in patients with human immunodeficiency virus‐associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored.METHODS.Cohorts of 6 patients were to be treated with BMS‐275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose‐limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response.RESULTS.Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3–54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de‐escalation decisions utilizing the apoptosis assay was not feasible.CONCLUSIONS.BMS‐275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better‐tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus‐associated KS. The apoptosis assay was not helpful in predicting response. Cancer 2008. © 2008 American Cancer Society.
Enzymatic activity of circulating proteasomes correlates with clinical behavior in patients with chronic lymphocytic leukemia
Authors: Ma Wanlong , Kantarjian Hagop , O'Brien Susan , Jilani Iman , Zhang Xi , Estrov Zeev , Ferrajoli Alessandra , Keating Michael , Giles Francis , Albitar Maher 
Published: January 2008

AbstractBACKGROUNDThe ubiquitin‐proteasome pathway has been implicated in the pathogenesis of many hematologic malignancies.METHODSThe authors measured proteasome peptidase activity levels in plasma samples from 225 patients with chronic lymphocytic leukemia (CLL) and correlated the results with clinical behavior. By using fluorogenic kinetic assays, the enzymatic activity levels of 3 proteasomes were measured: chymotrypsin‐like (Ch‐L), trypsin‐like (Tr‐L), and caspase‐like (Cas‐L).RESULTSAll activity levels were significantly higher in patients who had CLL compared with the levels in a control group of healthy volunteers (P < .001). Rai stage was correlated with Ch‐L activity (P < .001) but not with Cas‐L or Tr‐L activity. Levels of β2 microglobulin (B2M) were correlated with Ch‐L activity (correlation coefficient [R] = 0.4; P < .001) and with Cas‐L activity (R = 0.25; P = .001) but not with Tr‐L activity. Cas‐L activity as a continuous variable was a strong predictor of survival. Ch‐L and Cas‐L activity levels as categorical variables both were strong predictors of survival; Cas‐L activity was independent of B2M level but not of immunoglobulin variable heavy chain gene (IgVH) mutation status. However, the combination of elevated B2M levels (>3.2 mg/L) and Cas‐L activity (>1.32 pmoL/second/mL plasma) was associated with significantly shorter survival independent of IgVH mutation status.CONCLUSIONSThe current results indicated that measuring plasma proteasome activity has prognostic value in CLL that, when combined with B2M, can be independent of IgVH mutation status. Cancer 2008. © 2008 American Cancer Society.