bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of two protocols for sedation in pediatric oncology procedures
Authors: Crea Francesca , Ruggiero Antonio , Genovese Orazio , Tortorolo Luca , Zorzi Giulia , Chiaretti Antonio
Published: January 2008

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukemia (ALL). We investigated the safety and efficacy of two different protocols for pain relief in 20 children with ALL undergoing lumbar puncture. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. Vital and behavioural parameters, sedation and pain scores were recorded at different times during and after the procedure. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significative differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Our results show that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears more safe due to the lower incidence of side effects.
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, Russia

Clinopyroxenites, 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

Mechanically 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

The 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

The 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

The 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

Benzoylformate 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

Expression 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

The 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

Pd–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

The 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

The 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

The 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

BACKGROUND.

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

BACKGROUND

The ubiquitin‐proteasome pathway has been implicated in the pathogenesis of many hematologic malignancies.

METHODS

The 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).

RESULTS

All 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.

CONCLUSIONS

The 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.
Inhibition of proliferation of small intestinal and bronchopulmonary neuroendocrine cell lines by using peptide analogs targeting receptors
Authors: Kidd Mark , Schally Andrew V. , Pfragner Roswitha , Malfertheiner Maximillian V. , Modlin Irvin M.
Published: January 2008

BACKGROUND.

Currently, no consistently effective therapy is available to inhibit cell proliferation or metastasis of neuroendocrine tumor (NET) disease. The effects of 4 novel peptides were analyzed: a targeted cytotoxic analog of luteinizing hormone‐releasing hormone (LH‐RH) analog (AN‐152), a targeted cytotoxic analog of somatostatin (AN‐238), and 2 antagonists of growth hormone‐releasing hormone (GH‐RH) on 3 NET (carcinoid) cell lines that expressed respective peptide receptors.

METHODS.

The effects of the compounds were evaluated on cell proliferation in vitro using MTT uptake and Ki67 expression, apoptosis (caspase 3 expression and activity), and cell cycle parameters (DNA distribution).

RESULTS.

Proliferation of the LH‐RH receptor‐expressing lung NET, NCI‐H720 line, was inhibited 2‐fold by AN‐152 containing doxorubicin compared with the chemotherapy alone (IC50 of 9.1 nM vs 24 nM). This was associated with a reduction in Ki67 transcript and an increase in both caspase 3 mRNA levels and activity. Proliferation of the GH‐RH receptor expressing lung NET, NCI‐H727 line, was inhibited by both GH‐RH antagonists, the effects being mediated through changes in Ki67 expression, but not in caspase 3‐mediated apoptosis. The small intestinal NET, KRJ‐I line, was 8× more sensitive to inhibition by AN‐238 than to 2‐pyrolino‐doxorubicin, reflected by increased caspase 3 transcript as well as activity. AN‐238‐mediated growth inhibition culminated in complete G1 arrest.

CONCLUSIONS.

The data demonstrate GH‐RH antagonists or peptide‐linked antineoplastic agents such as AN‐152 and AN‐238 are effective inhibitors of NET proliferation in vitro. Because peptide receptors such as those for GH‐RH, LH‐RH, and SST subtypes are commonly expressed by NETs, the development of antineoplastic agents targeted to specific tumor receptors may provide a more efficacious strategy than systemic chemotherapeutic agents currently in use. Cancer 2008. © 2008 American Cancer Society.
High‐dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors
Authors: Shih Chie‐Schin , Hale Gregory A. , Gronewold Lindsey , Tong Xin , Laningham Fred H. , Gilger Elizabeth A. , Srivastava Deo Kumar , Kun Larry E. , Gajjar Amar , Fouladi Maryam
Published: January 2008

BACKGROUND.

High‐dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been reported to be effective in treating children with recurrent central nervous system (CNS) malignancies.

METHODS.

To evaluate the efficacy and toxicities of HDCT and ASCR, the medical records of 27 children with recurrent CNS malignancies who received such therapy at St. Jude Children's Research Hospital between 1989 and 2004 were reviewed.

RESULTS.

The median age at diagnosis was 4.5 years (range, 0.4–16.6 years) and that at ASCR was 6.7 years (range, 1.1–18.5 years). Diagnoses included medulloblastoma (13 patients), primitive neuroectodermal tumor (3 patients), pineoblastoma (2 patients), atypical teratoid rhabdoid tumor (2 patients), ependymoma (3 patients), anaplastic astrocytoma (2 patients), and glioblastoma multiforme (2 patients). The 5‐year overall and progression‐free survival (PFS) rates were 28.2% and 18.5%, respectively. The 5‐year PFS rate for patients aged <3 years at diagnosis (57.1%) was significantly better than older patients (5.0%) (P = .019). Among the 6 long‐term survivors (5 with M0 disease and 1 with M3 disease at diagnosis), 5 received both radiotherapy and HDCT as part of their salvage regimen; 4 were aged <3 years at diagnosis and had received chemotherapy only as part of frontline therapy. Two patients died of transplant‐related toxicities; 44% experienced grade 3 or 4 transplant‐related toxicities (toxicities were graded according to the National Cancer Institute Common Toxicity Criteria).

CONCLUSIONS.

HDCT with ASCR is not an effective salvage strategy for older children with recurrent CNS malignancies. The significantly better outcome in the younger cohort was most likely related to the use of radiotherapy as part of the salvage strategy. Cancer 2008. © 2008 American Cancer Society.
Effect of the number of lymph nodes sampled on postoperative survival of lymph node‐negative esophageal cancer
Authors: Greenstein Alexander J. , Litle Virginia R. , Swanson Scott J. , Divino Celia M. , Packer Stuart , Wisnivesky Juan P.
Published: January 2008

BACKGROUND

The presence of lymph node (LN) metastases in esophageal cancer has important prognostic and treatment implications. However, the optimal number of LNs that should be examined for accurate staging is controversial. In the current study, the association between survival and the number of LNs evaluated was examined in patients who underwent resection of lymph node‐negative (American Joint Committee on Cancer [AJCC] TNM stage I‐IIA) esophageal cancer.

METHODS

All patients were identified who underwent surgery for lymph node‐negative esophageal cancer between 1988 and 2003 from the Surveillance, Epidemiology, and End Results cancer registry. Patients were classified into 3 groups by the number of negative LNs sampled during surgery (≤10 LNs, 11‐17 LNs, and ≥18 LNs). Esophageal cancer‐specific survival was compared among these LN groups using Kaplan‐Meier curves. Stratified and Cox regression analyses were used to evaluate the association between survival and the number of negative LNs after adjusting for potential confounders.

RESULTS

A total of 972 patients were included in the study. Disease‐specific survival rates increased with a higher number of negative LNs. The 5‐year disease‐specific survival rate was 55% among patients with ≤10 negative LNs, compared with 66% and 75%, respectively, for those with 11 to 17 negative LNs and ≥18 negative LNs. The number of negative LNs was found to be significantly associated with survival in analyses stratified by tumor status. On multivariate regression controlling for age, race/ethnicity, sex, histology, tumor status, and postoperative radiotherapy, a higher number of negative LNs was found to be independently associated with higher disease‐specific survival.

CONCLUSIONS

The presence of LN metastases in patients with esophageal cancer appears to have important prognostic and treatment implications. Data from the current study suggest that patients undergoing surgical resection for esophageal cancer should have at least 18 LNs removed. Cancer 2008. © 2008 American Cancer Society.
A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma
Authors: Okuno Scott H. , Delaune Robert , Sloan Jeff A. , Foster Nathan R. , Maurer Matthew J. , Aubry Marie‐Christine , Rowland Kendrith M. , Soori Gamini S. , Nikcevich Daniel A. , Kardinal Carl G. , Northfelt Donald W. , Adjei Alex A.
Published: January 2008

BACKGROUND.

The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen.

METHODS.

A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m2 intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m2 intravenously on Day 1 on an every‐21‐days cycle (high‐dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m2 and epirubicin at a dose of 70 mg/m2 with the same schedule (low‐dose patient group).

RESULTS.

In the high‐dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3–34%). The median survival was 9.3 months (95% CI, 7.4–10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0–7.6 months). In the low‐dose patient group, the confirmed response rate was 7% (95% CI, 0–28%). The median survival was 5.7 months (95% CI, 4.7–8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7–5.6 months). Toxicity was moderate to severe. In the high‐doseand low‐dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high‐dose group but worsened in the low‐dose group.

CONCLUSIONS.

In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma. Cancer 2008. © 2008 American Cancer Society.
Deafferentiation‐associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain‐derived neurotrophic factor and acidic fibroblast growth factor
Authors: Glueckert Rudolf , Bitsche Mario , Miller Josef M. , Zhu Yaying , Prieskorn Diane M. , Altschuler Richard A. , Schrott‐Fischer Anneliese
Published: January 2008

Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3‐week‐delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate‐ and delayed‐treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation‐induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin‐positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers. J. Comp. Neurol. 507:1602–1621, 2008. © 2008 Wiley‐Liss, Inc.
Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation
Authors: Canto‐Soler M. Valeria , Huang Hu , Romero M. Soledad , Adler Ruben
Published: January 2008

We have hypothesized that the transcription factor CTCF may influence retinal cell differentiation by controlling Pax6 expression, because (1) CTCF has been shown to repress Pax6 expression in some tissues, and (2) Pax6 blocks the differentiation of retinal progenitor cells as photoreceptors and promotes their differentiation as nonphotoreceptor neurons. Our results show that, as predicted by this hypothesis, CTCF and Pax6 become segregated to different retinal cell types. The factors are initially coexpressed in the undifferentiated neuroepithelium, but already at that time they show complementary periphery‐to‐fundus gradients of distribution. As the retina laminates, Pax6 becomes restricted to ganglion and amacrine cells, and CTCF to the bipolar/Muller cell layer and the outer nuclear layer. Polymerase chain reaction analysis of laser capture microdissection samples and dissociated cells showed that both immature and differentiated photoreceptors are CTCF (+)/ Pax6 (−). Functional studies are now under way to further analyze the role of CTCF in retinal cell differentiation. Developmental Dynamics 237:758–767, 2008. © 2008 Wiley‐Liss, Inc.
Egfl7 knockdown causes defects in the extension and junctional arrangements of endothelial cells during zebrafish vasculogenesis
Authors: De Mazière Ann , Parker Leon , Van Dijk Suzanne , Ye Weilan , Klumperman Judith
Published: January 2008

The endothelial cell (EC) ‐specific secreted protein EGFL7 is important for tubulogenesis in newly forming blood vessels. We studied its role in vascular tube formation by a quantitative ultrastructural analysis of Egfl7‐knockdown zebrafish embryos. At 24 hours postfertilization, the endothelia of dorsal aorta (DA) and posterior cardinal vein (PCV) were correctly anchored to the hypochord and endoderm, respectively, but failed to expand into the vascular area. This resulted in vessels with reduced or split lumen and open sheets of ECs. Concomitantly, the organization of hematopoietic cells—identified by the presence of previously undescribed membrane tubules—between DA and PCV, and within the vessels, was severely disturbed. Strikingly, ectopic cell junctions occurred across the obstructed vessel lumen, on the luminal EC surfaces, which in control conditions never display junctions of any kind. These data suggest that Egfl7 provides ECs with a cue for their extension into the vascular area and in establishing EC cell polarity. Developmental Dynamics 237:580–591, 2008. © 2008 Wiley‐Liss, Inc.
Wtap is required for differentiation of endoderm and mesoderm in the mouse embryo
Authors: Fukusumi Yoshiyasu , Naruse Chie , Asano Masahide
Published: January 2008

Wilms' tumor 1‐associating protein (WTAP) was previously identified as a protein associated with Wilms' tumor‐1 (WT‐1) protein that is essential for the development of the genitourinary system. Although WTAP has been suggested to function in alternative splicing, stabilization of mRNA, and cell growth, its in vivo function is still unclear. We generated Wtap mutant mice using a novel gene‐trap approach and showed that Wtap mutant embryos exhibited defective egg‐cylinder formation at the gastrulation stage and died by embryonic day 10.5. Although they could form extraembryonic tissues and anterior visceral endoderm, Wtap mutant embryos and embryonic stem cells failed to differentiate into endoderm and mesoderm. The chimera analysis showed that Wtap in extraembryonic tissues was required for the formation of mesoderm and endoderm in embryonic tissues. Taken together, our findings indicate that Wtap is indispensable for differentiation of mesoderm and endoderm in the mouse embryo. Developmental Dynamics 237:618–629, 2008. © 2008 Wiley‐Liss, Inc.
Cell autonomous roles for AP‐2α in lens vesicle separation and maintenance of the lens epithelial cell phenotype
Authors: Pontoriero Giuseppe F. , Deschamps Paula , Ashery‐Padan Ruth , Wong Ryan , Yang Ying , Zavadil Jiri , Cvekl Ales , Sullivan Shelley , Williams Trevor , West‐Mays Judith A.
Published: January 2008

In this study, we have created a conditional deletion of AP‐2α in the developing mouse lens (Le‐AP‐2α mutants) to determine the cell‐autonomous requirement(s) for AP‐2α in lens development. Embryonic and adult Le‐AP‐2α mutants exhibited defects confined to lens placode derivatives, including a persistent adhesion of the lens to the overlying corneal epithelium (or lens stalk). Expression of known regulators of lens vesicle separation, including Pax6, Pitx3, and Foxe3 was observed in the Le‐AP‐2α mutant lens demonstrating that these genes do not lie directly downstream of AP‐2α. Unlike germ‐line mutants, Le‐AP‐2α mutants did not exhibit defects in the optic cup, further defining the tissue specific role(s) for AP‐2α in eye development. Finally, comparative microarray analysis of lenses from the Le‐AP‐2α mutants vs. wild‐type littermates revealed differential expression of 415 mRNAs, including reduced expression of genes important for maintaining the lens epithelial cell phenotype, such as E‐cadherin. Developmental Dynamics 237:602–617, 2008. © 2008 Wiley‐Liss, Inc.
Expression of the eight AMPA receptor subunit genes in the developing central nervous system and sensory organs of zebrafish
Authors: Hoppmann Verena , Wu Jun J. , Søviknes Anne Mette , Helvik Jon Vidar , Becker Thomas S.
Published: January 2008

The AMPA type glutamate receptors mediate the majority of fast synaptic transmission in the vertebrate nervous system. Whereas mammals have four subunit genes, Gria1‐4, zebrafish has retained a duplicated set of eight genes named gria1‐4a and b. We give here a detailed overview of the expression patterns of all eight zebrafish subunits within the developing central nervous system and sensory organs at 24, 48, and 72 hr after fertilization. Expression domains include distinct neuronal subsets in the developing forebrain, midbrain, hindbrain, and spinal cord, as well as in the ganglion‐ and inner nuclear layers of the retina. As a general rule, each pair of duplicated gria genes is differentially expressed, indicating subfunctionalization of AMPA receptor subunit expression in the teleost lineage. Our findings suggest that zebrafish can serve as a useful model system to investigate the role of AMPA receptors and their differential expression in the vertebrate nervous system. Developmental Dynamics 237:788–799, 2008. © 2008 Wiley‐Liss, Inc.
Synthesis of Copper Halide Coordination Polymers with Ligands Formed by In Situ Cyclization of 2‐Aminopyrimidine and Ethanol
Authors: Bi Minghui , Li Guanghua , Hua Jia , Lin Yingjie , Cao Junjun , Shi Zhan , Feng Shouhua
Published: January 2008

The design and synthesis of coordination polymers from transition metals and organic ligands have been extensively studied for their crystallographic diversity and potential applications. Recently, the synthesis of coordination polymers by hydro(solvo)thermal in situ metal/ligand reactions has drawn great interest because of its potential to generate novel coordination architectures and new organic reactions. As described in our manuscript, the nitrogen heterocyclic 2,3‐dihydroimidazo[1,2‐a]pyrimidine (C6H7N3) ligand was synthesized by an in situ reaction starting from 2‐aminopyrimidine and ethanol. At the same time, two luminescent copper halide coordination polymers, (CuCl)3C6H7N3 and (CuI)2C6H7N3, were assembled under solvothermal conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Infrahuman outgroup or suprahuman ingroup: The role of nationalism and patriotism in the infrahumanization of outgroups
Authors: Viki G. Tendayi , Calitri Raff
Published: January 2008

Previous research has shown that people are more likely to attribute uniquely human emotions to their ingroup than an outgroup (infrahumanization). In the current research, we examine whether these research findings are an indication of the infrahumanization of outgroups or the suprahumanization of the ingroup. We examined the role of nationalism and patriotism in the attribution of secondary emotions to groups. In line with the infrahumanization argument, we obtained a significant positive relationship between nationalism and the differential attribution of secondary emotions to the ingroup versus outgroup. In contrast, patriotism was negatively related to the differential attribution of secondary emotions. These findings indicate that the differential attribution of secondary emotions to the ingroup (vs. outgroup) is an indication of the derogation or infrahumanization of outgroups. Copyright © 2008 John Wiley & Sons, Ltd.
Generation of synthetic sequences of half‐hourly temperature
Authors: Magnano L. , Boland J. W. , Hyndman R. J.
Published: January 2008

We present tools to generate synthetic sequences of half‐hourly temperatures with similar statistical characteristics to observed historical data. Temperatures are generated using a combination of daily and half‐hourly temperature models which account for intra‐day and intra‐year seasonality, as well as short‐and long‐term serial correlations. Details of the model estimation are given as well as a description of the synthetic generation. Copyright © 2008 John Wiley & Sons, Ltd.
Toluene vapor remediation in a continuous packed bed loop bioreactor
Authors: Nikakhtari Hossein , Hill Gordon A.
Published: January 2008

An external loop airlift bioreactor with a small amount (99% porosity) of stainless steel mesh packing inserted in the riser section was used for bioremediation of a toluene polluted air stream. The packing enhanced VOC and oxygen mass transfer rates and provided a large surface area for cell immobilization. Using a mixed culture, fed‐batch and continuous runs at five different dilution rates were completed with toluene in the polluted air as the only carbon source. Above 99% and 93.6% toluene removals were achieved at toluene loading rates up to 88.1 and 149.1 g/(m3 h), respectively. The bioreactor responded quickly to a toluene load shock of 33 g/(m3 h) at high inlet toluene loadings. After 185.8 days operation, no plugging problems were observed in the column. A mathematical model is shown to accurately predict transient and steady state data. © 2008 American Institute of Chemical Engineers Environ Prog, 2008
Go out or stay in? The effects of zero tolerance laws on alcohol use and drinking and driving patterns among college students
Authors: Liang Lan , Huang Jidong
Published: January 2008

Zero tolerance laws make it illegal per se for anyone under age 21 to drive with any measurable amount of blood alcohol. Although a link has been established between zero tolerance laws and lower motor vehicle fatalities, research has not produced strong evidence on how zero tolerance laws influence individual alcohol use and drinking and driving behaviors. Using a unique data set and a difference‐in‐difference‐in‐difference‐type research design, we are able to analyze a number of pathways through which zero tolerance laws can work among an important underage population, college students. We find that zero tolerance laws reduce drinking and driving among college students. Further analysis of our detailed alcohol use measures suggests that zero tolerance laws are particularly effective at reducing the probability of driving after drinking for those who reported drinking away from home. Published in 2008 by John Wiley & Sons, Ltd.
Akt1 inhibition by RNA interference sensitizes human non‐small cell lung cancer cells to cisplatin
Authors: Lee Myoung Woo , Kim Dae Seong , Min Na Young , Kim Heung Tae
Published: January 2008

Akt/protein kinase B signaling is very important for cancer cell survival and growth when cells are exposed to various apoptotic stimuli. Akt is constitutively activated in NSCLC cells and is a potential target for enhancing the cytotoxicity of chemotherapeutic agents in treatment of NSCLC. In our study, we investigated whether down‐regulating Akt1 using RNAi techniques can enhance sensitivity to cisplatin in NSCLC cells. An siRNA targeting Akt1 significantly decreased the protein level of Akt1 and the activity of ERK. Treatment of these cells with 20 μM cisplatin increased apoptotic cell death ∼2.6‐fold compared to cells transfected with a scrambled siRNA. While Akt activity was slightly reduced, ERK activity was greatly increased in cells treated with cisplatin alone. Pretreatment of these cells with the selective MEK inhibitor U0126 effectively reduced the level of cisplatin‐induced apoptosis. These results imply that cisplatin‐induced MEK/ERK activation appears to mediate apoptotic cell death, but that constitutively activated Akt1 and/or ERK pathway may mediate resistance to cisplatin in NSCLC cells. Taken together, our data demonstrate that down‐regulation of Akt1 using RNAi enhances the chemosensitivity of NSCLC cells to cisplatin. © 2008 Wiley‐Liss, Inc.