bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Investigations and Experiments for the Analysis of Mixing of Highly Viscous Fluids in a Rotor‐Stator Mixer
Authors: Smuda Christina , Piesche Manfred
Published: July 2012

Mithilfe der numerischen Strömungsmechanik, unterstützt durch Experimente, wurde ein Rotor‐Stator‐Mischer hinsichtlich seines Betriebs‐ und Mischverhaltens untersucht. Für die isoviskose Vermischung konnten Ähnlichkeitsgesetze hergeleitet werden, die das Betriebsverhalten in Form dimensionsloser Kennzahlen beschreiben. Der Vergleich der Ergebnisse aus der numerischen Strömungssimulation mit den experimentellen Daten zeigt eine gute Übereinstimmung. In weiteren Simulationen und Experimenten wurden außerdem das Volumenstrom‐ und das Viskositätsverhältnis der zu vermischenden Komponenten mit newtonschen Stoffeigenschaften variiert und deren Einfluss auf die Mischgüte analysiert.
Plastics – Granulate and/or Pelletize?
Authors: Mürb Reinhardt‐Karsten
Published: July 2012

Die vermeintlich einfache verfahrenstechnische Operation zur Herstellung von Kunststoffgranulat eröffnet bei näherer Betrachtung eine Vielfalt von einzelnen Aspekten. Trotz vieler, meist empirischer Untersuchungen gibt es noch viel zu erforschen. Dabei werden von Produkt und Werkzeugen viele Teildisziplinen berührt: Materialwissenschaften, Thermodynamik, Rheologie, Festigkeitslehre, Tribologie, Maschinenlehre etc. Granulieren oder Pelletieren sind Mittel zum Zweck, um den Kunststoff in eine transportier‐ und dosierbare Form zu bringen. Der Beitrag vergleicht die Verfahren und weist auf Potenziale für weiterführende wissenschaftliche Untersuchungen hin.
Research Secures Raw Materials for High‐Tech Made in Germany
Authors: Mennicken Lothar , Jacobi Andreas , Degenhardt Anja
Published: July 2012

Die deutsche Bundesregierung hat mit ihrer Rohstoffstrategie auf mögliche Engpässe bei nicht‐energetischen, mineralischen Rohstoffen reagiert. Das Bundesministerium für Bildung und Forschung (BMBF) unterstützt die ressortübergreifende Strategie sowohl mit seiner institutionellen Förderung als auch mit der spezifischen Projektförderung. Das neue FuE‐Programm Wirtschaftsstrategische Rohstoffe für den Hightech‐Standort Deutschland ist wegweisend. Verschiedene rohstoffbezogene Fördermaßnahmen innerhalb des BMBF‐Rahmenprogramms Forschung für nachhaltige Entwicklungen werden beschrieben.
B(C6F5)3 as a Highly Effective Catalyst for the Phosphoryl Transfer Reaction
Authors: Xue Weihua , Zhang Lifen
Published: July 2012

The phosphoryl transfer reactions of diphenyl chlorophosphate with a wide range of alcohols were catalyzed by tris(pentafluorophenyl)boron [B(C6F5)3], giving the corresponding phosphate esters in excellent yields. This methodology has advantages over older ones because it employs the easily handled B(C6F5)3, avoids the side reaction, and has shorter reaction time.
DNA‐Templated Silver Nanoclusters Formation at Gold Electrode Surface and Its Application to Hydrogen Peroxide Detection
Authors: Xu Yuanyuan , Chen Yangyang , Yang Nana , Sun Lizhou , Li Genxi
Published: July 2012

In this work, we have prepared Ag nanoclusters (Ag NCs) at gold electrode surface by using thiol‐modified oligodeoxynucleotide consisting of eighteen cytosine deoxyribonucleotides (polyC18) as template and NaBH4 as reducing agent. Experimental results show that Ag nanoclusters (Ag NCs) can be formed around the template polyC18, while the formation can be characterized with electrochemical method. Further studies reveal that the fabricated Ag NCs may display high catalytic activity for the reduction of hydrogen peroxide (H2O2), which can be further used for the detection of H2O2.
Designs, Synthesis, Characterization and Direct Electrochemistry of Zinc‐Porphyrin Bearing Pyrene Noncovalent Functionalized Graphene Oxide Sheet
Authors: Bi Chun , Li Yongjie , Chen Haowen , Yin Gui , Zhu Junjie
Published: July 2012

We have designed and synthesis a new compound of zinc‐porphyrin bearing four pyrene groups (ZnP‐t‐P(py)4) and prepared a new hybrid materials of ZnP‐t‐P(py)4 with graphene oxide (GO) via non‐covalent interactions. The ZnP‐t‐P(py)4, along with four pendant pyrene entities ZnP‐t‐P(py)4, stacking on the (GO) surface due to π‐ π interactions, has been revealed by AFM measurements. FTIR, UV‐vis absorption confirm the non‐covalent functionalization of the GO. Raman spectral measurements revealed the electronic structure of the GO to be intact upon hybrid formation. In this donor‐acceptor nanohybrid, the fluorescence of photoexcited ZnP‐t‐P(py)4 is effectively quenched by a possible electron‐transfer process. The fluorescence and photoelectrical response measurements also showed that this hybrid may act as an efficient photoelectric conversion material for optoelectronic applications.
Photoelectrochemical Detection of Glucose by Using an Enzyme‐Modified Photoelectrode
Authors: Zhao Changzhi , Zhang Zhaoxia , Zhao Ying , Yu Jia
Published: July 2012

A new photoelectrochemical method for the determination of glucose based on the photoelectrochemical effect of poly(thionine) photoelectrode to hydrogen peroxide (H2O2) was reported. The H2O2‐sensitive photoelectrode was fabricated by electropolymerizing thionine on the surface of ITO electrode. And then glucose oxidase was immobilized on the photoelectrode via the aid of chitosan enwrapping, forming an enzyme‐modified photoelectrode. The photoelectrode was employed as an electron acceptor; H2O2 from the catalytic reaction of enzyme was employed as an electron donor, developing an analytical method of glucose without hydrogen peroxidase. In the paper, the photoelectrochemical effects of photoelectrode to H2O2 and glucose were studied. The effects of the bias voltage and the electrolyte pH on the photocurrent were investigated. The linear response of glucose concentrations ranged from 0.05 to 2.00 mmol/L was obtained with a detection limit of 22.0 µmol/L and sensitivity of 73.2 nA/(mmol·L−1). The applied feasibility of method was acknowledged through monitoring the glucose in practical samples.
Genetic and epigenetic alterations in primary colorectal cancers and related lymph node and liver metastases
Authors: Miranda Elena , Bianchi Paolo , Destro Annarita , Morenghi Emanuela , Malesci Alberto , Santoro Armando , Laghi Luigi , Roncalli Massimo
Published: July 2012

BACKGROUND:

Colorectal cancer (CRC) prognosis and survival are strictly related to the development of distant metastases. New targeted therapies have increased patient survival, but the objective response rate is still very limited, partially because of a traditional focus on designing treatment according to the molecular profile of the primary tumor regardless the diversity between the primary tumor and metastases. The objective of this study was to evaluate the presence of molecular heterogeneity during metastatic progression and its potential impact on clinical treatment.

METHODS:

The authors analyzed v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12 mutations, the v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) thymine to adenine substitution at codon 1788, and tumor protein 53 (p53) mutations and investigated promoter methylation of Ras association (RalGDS/AF‐6) domain family member 1 protein (RASSF1a), E‐cadherin, and cyclin‐dependent kinase inhibitor 2A (p16INK4a) in 101 primary CRCs (67 stage III and 34 stage IV) and related lymph node and liver metastases.

RESULTS:

Lymph node metastases were characterized by fewer alterations compared with primary tumors and liver metastases, especially KRAS (P = .03) and p16INK4a (P = .05). Genetic changes, when detectable in metastases, mostly were retained from the primary tumor, whereas epigenetic changes more frequently were acquired de novo. Overall, 31 distinct CRC molecular profiles were detected, none of which characterized a particular tumor stage. When the metastatic lesions also were included in the profiles, there were 53 distinct molecular profiles in 67 patients with stage III disease and 34 distinct molecular profiles in 34 patients with stage IV disease.

CONCLUSIONS:

Lymph node and liver metastases appear to originate in clonally different processes, with more molecular alterations occurring in distant metastases than in lymph node metastases and with elevated heterogeneity of the primary tumor. Thus, potential prognostic targets should be carefully evaluated for their heterogeneity in both primary tumors and distant metastases to avoid erroneous misclassification. Cancer 2013. © 2012 American Cancer Society.
Chalcogenoalkynes: Precursors for the Regioselective Preparation of 2‐Chalcogeno‐1‐halonaphthalenes through [4+2] Cycloaddition
Authors: Mantovani Anderson C. , Back Davi F. , Zeni Gilson
Published: July 2012

Chalcogenoalkynes and o‐alkynylbenzaldehydes reacted in the presence of copper(II) salt to give the [4+2] cycloadducts 2‐chalcogeno‐1‐halonaphthalenes in good yields (46–89 %) and high regioselectivities. The methodology was carried out by using CuCl2 or CuCl2/LiBr in 1,2‐dichloroethane (DCE) at 80 °C. The potential and generality of this system was evaluated by using a variety of chalcogenoalkynes including aromatic, substituted aromatic, and aliphatic substrates having both sulfur and selenium atoms. In this sequence, due to the ability of the chalcogen atoms to stabilize charges, these substituents exert regiocontrol that guides the selectivity.
Apixaban: a new option for stroke prevention in atrial fibrillation?
Authors: Cox Andrew , Ghani Saqib , Camm A John
Published: July 2012

Atrial fibrillation is the most common sustained cardiac arrhythmia and its prevalence is set to double by 2050. Of the possible treatments for the condition, only antithrombotic therapy has demonstrated a mortality benefit. Until recently, the gold‐standard treatment was warfarin; in those patients for whom this was contraindicated, aspirin was used. However, over the last two years, several new agents have been developed, the most recent of which is the factor Xa inhibitor apixaban [Eliquis]. Two large randomised controlled trials comparing apixaban with aspirin and warfarin were recently reported. This Drug profile outlines the significant benefits of apixaban in reducing mortality, stroke risk and major bleeding events in atrial fibrillation.
Future of pain management: current advances and new targets
Authors: Aldridge Susan
Published: July 2012

A wide range of new targets in the management of pain were discussed by clinician and industry specialists at the Visiongain Annual Pain Management conference in July
Terpenoids from Loxocalyx urticifolius
Authors: He Dahai , Xu Xuemin , Zhou Yan , Deng Wenlong , Xia Bin , Ding Lisheng
Published: July 2012

Two new diterpenoids, loxocalyxin A (1) and 13‐epiloxocalyxin A (2), and two new sesquiterpenoids, loxocalyxins B and C (3 and 4, resp.), together with three known compounds, were isolated from the MeOH extract of the whole plant of Loxocalyx urticifolius Hemsl. The structures of the new compounds were established by means of spectroscopic analysis including one‐ and two‐dimensional NMR spectroscopy. All new structures were confirmed by X‐ray crystallographic analysis. Their absolute configurations were established.
Ultrasound‐Promoted Catalyst‐Free Synthesis of 2,2′‐(1,4‐Phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] Derivatives
Authors: Azarifar Davood , Sheikh Davood
Published: July 2012

A convenient approach to 2,2′‐(1,4‐phenylene)bis[1‐acetyl‐1,2‐dihydro‐4H‐3,1‐benzoxazin‐4‐one] derivatives 4 was explored employing the one‐pot condensation of anthranilic acids (=2‐aminobenzoic acids) 1 with terephthalaldehyde (=benzene‐1,4‐dicarboxaldehyde; 2) under ultrasound‐irradiation conditions (Scheme 1). The reactions proceeded smoothly in the presence of excess Ac2O in the absence of any other catalyst and solvent to afford the respective products in high yields.
Mechanistic Investigation of the Ring Opening in the Staudinger Cycloaddition Involving Ketenes with Electron‐Withdrawing Substituents
Authors: Mo Shanyan , Xu Jiaxi
Published: July 2012

The cycloaddition of ketenes and imines (Staudinger cycloaddition) is a general method for the synthesis of various β‐lactams. However, reactions of imines and ketenes with electron‐withdrawing substituents produce α,β‐unsaturated alkenamides, ring‐opening products of the intermediates generated from imines and the ketenes, even as sole products, besides the desired β‐lactams. The mechanism of the formation of α,β‐unsaturated alkenamides was investigated. The results indicate that the α,β‐unsaturated alkenamides are generated via a base‐induced CC bond isomerization followed by electrocyclic ring opening of the formed azacyclobutenes (=1,2‐dihydroazetes; cf. Scheme 3).
Stereoselective Total Synthesis of Botryolide E
Authors: Veeranjaneyulu Boyapati , Srilatha Malampati , Reddy Gandolla Chinna , Das Biswanath
Published: July 2012

The stereoselective total synthesis of the naturally occurring γ‐lactone derivative botryolide E (1) was accomplished with acetaldehyde as the starting material (Scheme 2). The asymmetric allyl boration, asymmetric dihydroxylation, chelation‐mediated diastereoselective vinylation, and ring‐closing metathesis reaction are the key steps. The method can conveniently be utilized for the preparation of other related γ‐lactone derivatives.
Three New Sucrose Fatty Acid Esters from Equisetum hiemale L.
Authors: Cheng Jin‐Tang , He Juan , Li Xing‐Yao , Wu Xing‐De , Shao Li‐Dong , Dong Liao‐Bin , Deng Xu , Gao Xiu , Peng Li‐Yan , Cheng Xiao , Li Yan , Zhao Qin‐Shi
Published: July 2012

Three new monosubstituted sucrose fatty acid esters, 1–3, were isolated from Equisetum hiemale L., together with nine known compounds, 4–12. Their structures were elucidated by spectroscopic analyses. Compounds 5, 6, and 10–12 were isolated from the title plant for the first time. All these compounds were evaluated for their cytotoxic activity. However, none of them was cytotoxic.
A Novel One‐Pot Synthesis of Fully Substituted Thiophen‐2(3H)‐ones Using N,N‐Disubstituted Thioamides
Authors: Zali‐Boeini Hassan , Pourjafarian Fatemeh
Published: July 2012

A new one‐step synthesis of highly substituted thiophen‐2(3H)‐one derivatives was developed. 2‐Aryl‐1‐(morpholin‐4‐yl)ethanethiones were reacted with 2‐chloro‐2‐phenylacetyl chloride in DMF in the presence of a base to give the title compounds in moderate‐to‐good yields.
Deviation of the KempsterLipson Law from Linearity
Authors: Fábry Jan , Kopecký Miloš , Krupková Radmila
Published: July 2012

It is shown that the larger organic molecules composed of C, H, N, and O at most crystallizing in the voluminous unit cells tend to be more loosely packed than those that crystallize in the unit cells with small volumes. This is demonstrated by the deviation from the linear relationship (KempsterLipson law) between the unit‐cell volumes and the sum of the non‐H‐atoms in the unit cell. This deviation can be distinguished from the effect of the varying number of H‐atoms in the described compounds: the ratio of the non‐H‐atom to the H‐atoms converges to a constant value close to 1 towards the large unit‐cell volumes. The proportion of the disordered structures increases towards the large unit‐cell volumes and thus correlates with the less dense packing of the large molecules. The deviation of the KempsterLipson law from linearity can be interpreted as the manifestation of decreasing ability of a crystallization of large molecules.
1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Enol Ethers and Ketene Acetals as Cycloaddition Partners
Authors: Huisgen Rolf , Desmaison Gonzalo Urrutia
Published: July 2012

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile ((E)‐ and (Z)‐BTE, resp., =(E)‐ and (Z)‐2,3‐bis(trifluoromethyl)but‐2‐enedinitrile) were used as a stereochemical probe in studying (2+2) cycloadditions of acceptor with donor alkenes. The additions to methyl (E)‐ and (Z)‐propenyl ether gave rise to the eight conceivable cyclobutanes 8, although in different ratios in reactions of (E)‐ and (Z)‐BTE. The 19F‐NMR data served the structural assignment and the quantitative analysis. The mechanistic discussion is based on rotations and ring closures of the assumed 1,4‐zwitterionic intermediates. Dimethylketene dimethyl acetal, methylketene dimethyl acetal, and ketene diethyl acetal show an increasing rate in their reactions with BTE as well as in the equilibration of the cycloadducts.
1,2‐Oxazine N‐Oxides as Catalyst Resting States in Michael Additions of Aldehydes to Nitro Olefins Organocatalyzed by α,α‐Diphenylprolinol Trimethylsilyl Ether
Authors: Seebach Dieter , Sun Xiaoyu , Sparr Christof , Ebert Marc‐Olivier , Schweizer W. Bernd , Beck Albert K.
Published: July 2012

By combining enamines, derived from aldehydes and diphenylprolinol trimethylsilyl ether (the Hayashi catalyst), with nitroethenes ((D6)benzene, 4‐Å molecular sieves, room temperature) intermediates of the corresponding catalytic Michael‐addition cycles were formed and characterized (IR, NMR, X‐ray analysis; Schemes 3–6 and Fig. 1–3). Besides cyclobutanes 2, 1,2‐oxazine N‐oxide derivatives 3–6 and 8 have been identified for the first time, some of which are very stable compounds. It may not be a lack of reactivity (between the intermediate enamines and nitro olefins) that leads to failure of the catalytic reactions (Schemes 3–5) but the high stability of catalyst resting states. The central role zwitterions play in these processes is discussed (Schemes 1 and 2).
Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses
Authors: Rucklidge Julia J , Andridge Rebecca , Gorman Brigette , Blampied Neville , Gordon Heather , Boggis Anna
Published: July 2012

Objective

To compare two micronutrient (vitamins and minerals) formulas (Berocca™ and CNE™) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22nd2011 in Christchurch, New Zealand.

Methods

91 adults experiencing heightened anxiety or stress 2–3 months following the earthquake were randomized to Berocca™, CNE™ low dose (CNE4), or CNE™ high dose (CNE8), for 28 days and monitored weekly via on‐line questionnaires and followed 1 month post‐trial. A nonrandomized control group (n = 25) completed questionnaires at baseline and 4 weeks.

Results

All treatment groups experienced significant declines in psychological symptoms (p < .001). CNE™ groups experienced greater reduction in intrusive thoughts as compared with Berocca™ (p = .05), with no group differences on other measures of psychological symptoms. However, CNE8 group reported greater improvement in mood, anxiety, and energy (p < .05) with twice as many reporting being “much” to “very much” improved and five times more likely to continue taking CNE™ post‐trial than Berocca™ group. Treated participants had better outcomes on most measures over 4 weeks as compared to controls.

Conclusions

This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909. Copyright © 2012 John Wiley & Sons, Ltd.
Automated double red‐cell phlebotomy for the treatment of erythrocytosis
Authors: Choe Won Ho , Park Borae G. , Lee Kyoo‐Hyung , Lee Je‐Hwan , Lee Jung‐Hee , Kwon Seog‐Woon
Published: July 2012

Background: Phlebotomy has been used as a primary method for the treatment of erythrocytosis. As a new phlebotomy method, we used an automated component collection system (Alyx, Fenwal), which has been used to obtain two units of leukoreduced red blood cells (RBCs) from donors. We evaluated the effectiveness of “double red‐cell” phlebotomy (DRP) and compared it with conventional “whole‐blood” phlebotomy (WBP). Materials and Methods: We have performed a total of 596 phlebotomies in 158 patients with erythrocytosis between June 2008 and November 2011. Forty patients underwent 84 DRPs and 118 patients underwent 512 WBPs. We removed 360–420 mL of RBCs in DRP and 360–600 mL of whole blood in WBP according to patient's total blood volume (TBV). Changes in hematologic parameters after phlebotomy were compared. Results: DRP removed more RBC volume (399.4 ± 20.2 mL vs. 235.9 ± 29.8 mL, P < 0.05) and lowered more hematocrit than WBP (6.9% ± 2.3% vs. 3.0% ± 1.7%, P < 0.05). Hematocrit reduction per kilogram of body weight was higher by DRP than WBP (0.106% ± 0.043% vs. 0.039% ± 0.025%, P < 0.05). Mild adverse events occurred in 32.5% (13/40) during DRP and 4.2% (5/118) during WBP. Conclusion: DRP lowered more RBC mass than WBP by selectively removing more RBC volume with less TBV. DRP can be an effective and safe technique for the treatment of erythrocytosis. J. Clin. Apheresis 27:255–259, 2012. © 2012 Wiley Periodicals, Inc.
Shaping the nucleus: Factors and forces
Authors: Walters Alison D. , Bommakanti Ananth , Cohen‐Fix Orna
Published: July 2012

Take a look at a textbook illustration of a cell and you will immediately be able to locate the nucleus, which is often drawn as a spherical or ovoid shaped structure. But not all cells have such nuclei. In fact, some disease states are diagnosed by the presence of nuclei that have an abnormal shape or size. What defines nuclear shape and nuclear size, and how does nuclear geometry affect nuclear function? While the answer to the latter question remains largely unknown, significant progress has been made towards understanding the former. In this review, we provide an overview of the factors and forces that affect nuclear shape and size, discuss the relationship between ER structure and nuclear morphology, and speculate on the possible connection between nuclear size and its shape. We also note the many interesting questions that remain to be explored. J. Cell. Biochem. 113: 2813–2821, 2012. © 2012 Wiley Periodicals, Inc.
Prokaryotic Nε‐lysine acetylomes and implications for new antibiotics
Authors: Xie Longxiang , Li Wu , Xie Jianping
Published: July 2012

Protein Nε‐acetylation, a post‐translational modification widespread in eukaryotes and prokaryotes, has been intensively explored due to its crucial roles in multitudinous physiologic events including transcriptional regulation, metabolic regulation, etc. The particular hotspot is the relationship between acetylation and metabolic regulation. Protein acetylation major types and functions thereof, prokaryotic acetyltransferase, deacetylases, and acetylation sites of enzymes related to glycometabolism, together with the cross‐talk between acetylation and other modification, such as the phosphorylation were summarized, with emphases on those from Mycobacteria. J. Cell. Biochem. 113: 3601–3609, 2012. © 2012 Wiley Periodicals, Inc.
Aquaporin 2‐increased renal cell proliferation is associated with cell volume regulation
Authors: Di Giusto Gisela , Flamenco Pilar , Rivarola Valeria , Fernández Juan , Melamud Luciana , Ford Paula , Capurro Claudia
Published: July 2012

We have previously demonstrated that in renal cortical collecting duct cells (RCCD1) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation. In this study, we investigated the mechanisms involved in this process, focusing on the putative link between AQP2 expression, cell volume changes, and regulatory volume decrease activity (RVD). Two renal cell lines were used: WT‐RCCD1 (not expressing aquaporins) and AQP2‐RCCD1 (transfected with AQP2). Our results showed that when most RCCD1 cells are in the G1‐phase (unsynchronized), the blockage of barium‐sensitive K+ channels implicated in rapid RVD inhibits cell proliferation only in AQP2‐RCCD1 cells. Though cells in the S‐phase (synchronized) had a remarkable increase in size, this enhancement was higher and was accompanied by a significant down‐regulation in the rapid RVD response only in AQP2‐RCCD1 cells. This decrease in the RVD activity did not correlate with changes in AQP2 function or expression, demonstrating that AQP2—besides increasing water permeability—would play some other role. These observations together with evidence implying a cell‐sizing mechanism that shortens the cell cycle of large cells, let us to propose that during nutrient uptake, in early G1, volume tends to increase but it may be efficiently regulated by an AQP2‐dependent mechanism, inducing the rapid activation of RVD channels. This mechanism would be down‐regulated when volume needs to be increased in order to proceed into the S‐phase. Therefore, during cell cycle, a coordinated modulation of the RVD activity may contribute to accelerate proliferation of cells expressing AQP2. J. Cell. Biochem. 113: 3721–3729, 2012. © 2012 Wiley Periodicals, Inc.
Acyclic Chromatic Indices of Planar Graphs with Girth At Least 4
Authors: Shu Qiaojun , Wang Weifan , Wang Yiqiao
Published: July 2012

An acyclic edge coloring of a graph G is a proper edge coloring such that no bichromatic cycles are produced. The acyclic chromatic index of G is the smallest integer k such that G has an acyclic edge coloring using k colors. Fiamik (Math. Slovaca 28 (1978), 139–145) and later Alon et al. (J Graph Theory 37 (2001), 157–167) conjectured that for any simple graph G with maximum degree Δ. In this article, we confirm this conjecture for planar graphs of girth at least 4.
A Sufficient Condition for Edge Chromatic Critical Graphs to Be Hamiltonian—An Approach to Vizing's 2‐Factor Conjecture
Authors: Luo Rong , Zhao Yue
Published: July 2012

In this article, we consider Vizing's 2‐Factor Conjecture which claims that any Δ‐critical graph has a 2‐factor, and show that if G is a Δ‐critical graph with n vertices satisfying , then G is Hamiltonian and thus G has a 2‐factor. Meanwhile in this article, we also consider long cycles of overfull critical graphs and obtain that if G is an overfull Δ‐critical graph with n vertices, then the circumference of G is at least min.© 2012 Wiley Periodicals, Inc. J. Graph Theory 00: 1‐14, 2012
Molecular Docking Study Based on Pharmacophore Modeling for Novel PhosphodiesteraseIV Inhibitors
Authors: Çifci Gülşah , Aviyente Viktorya , Akten E. Demet
Published: July 2012

In this study, pharmacophore modelling was carried out for novel PhosphodiesteraseIV (PDEIV) inhibitors. A pharmacophore‐based virtual screening, which resulted in 1959 hit compounds was performed with six chemical databases. The pharmacophore screening was proven to be successful in discriminating active and inactive inhibitors using a set of compounds with known activity obtained from ChEMBL database. Furthermore, the Lipinski’s rule of five was applied for physicochemical filtering of the hit molecules and this yielded 1840 compounds. Three docking software tools, AutoDock 4.0, AutoDock Vina, and Gold v5.1 were used for the docking process. All 1840 compounds and the known selective inhibitor, rolipram, were docked into the active site of the target protein. A total of 234 compounds with all three scoring values higher than those of rolipram were determined with the three docking tools. The interaction maps of 14 potent inhibitors complexed with PDEIV B and D isoforms have been analyzed and seven key residues (Asn 395, Gln 443, Tyr 233, Ile 410, Phe 446, Asp 392, Thr 407) were found to interact with more than 80 % of the potent inhibitors. For each one of the 234 hit compounds, using the bound conformation with the highest AutoDock score, the interacting residues were determined. 117 out of 234 compounds are found to interact with at least five of the seven key residues and these were selected for further evaluation. The conformation with the highest AutoDock score for each 117 compounds were rescored using the DSX scoring function. This yielded a total of 101 compounds with better score values than the natural ligand rolipram. For ADME/TOX calculations, the FAF‐Drugs2 server was used and 32 out of 101 compounds were found to be non‐toxic.
Promoting role of cholecystokinin 2 receptor (CCK2R) in gastrointestinal stromal tumour pathogenesis
Authors: Quattrone Anna , Dewaele Barbara , Wozniak Agnieszka , Bauters Marijke , Vanspauwen Vanessa , Floris Giuseppe , Schöffski Patrick , Chibon Frederic , Coindre Jean‐Michel , Sciot Raf , Debiec‐Rychter Maria
Published: July 2012

The cholecystokinin 2 receptor (CCK2R/CCKBR) is expressed in gastrointestinal stromal tumours (GISTs). We sought to investigate the role of CCK2R in GIST pathogenesis. Molecular characterization of CCK2R was performed on a heterogeneous cohort of 50 GISTs. In addition, CCK2R expression was evaluated by immunohistochemistry (IHC), using tissue microarray (TMA) containing 292 GISTs, two cases of hyperplasia of interstitial Cajal's cells (ICC) and six gastric microscopic GISTs. Mono‐allelic loss of the CCK2R/11p15 allele was identified in 13.7% of GISTs, having no impact on the level of CCK2R transcript expression. No CCK2R mutations were found. The CCK2Ri4sv, CCK2R splice variant with retention of intron 4 was detected in six of 20 tumours analysed. Wild‐type CCK2R transcripts were commonly expressed (57.1% of cases) and this expression was highly correlated with gastric primary site of GISTs (p < 0.001). At the protein level, expression of CCK2R in incidental ICC hyperplasia and early stages of gastric GIST development was documented, and its gastric association was confirmed on GIST‐TMA by IHC. To explore the in vivo effect of CCK2R activation on tumour growth, gastrin versus placebo was administered intraperitoneally in nude mice carrying human GIST xenografts. The tumour volume was followed for 10 weeks. The effect of this stimulation on tumour cell proliferation/apoptosis was assessed by IHC and KIT/PKC‐θ signalling was evaluated by western blotting (WB). In vivo experiments showed a two‐fold increase in the volume of tumours which were exposed to gastrin in comparison with non‐exposed controls (p = 0.03), with a significant increase in mitotic activity (p = 0.04) and Ki‐67 proliferation index (p = 0.008). By WB, gastrin stimulation resulted in hyper‐activation of KIT and PKC‐θ kinases, and in evident PI3K‐AKT pathway over‐activation. Our results indicate a promoting role of CCK2R on GIST tumourigenesis, particularly in tumours of gastric origin. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF‐A and TGFβ2 in vascular abnormalization
Authors: Dieterich Lothar C , Mellberg Sofie , Langenkamp Elise , Zhang Lei , Zieba Agata , Salomäki Henriikka , Teichert Martin , Huang Hua , Edqvist Per‐Henrik , Kraus Theo , Augustin Hellmut G , Olofsson Tommie , Larsson Erik , Söderberg Ola , Molema Grietje , Pontén Fredrik , Georgii‐Hemming Patrik , Alafuzoff Irina , Dimberg Anna
Published: July 2012

Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour‐associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non‐malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF‐A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF‐A, TGFβ2 may represent a new target for vascular normalization therapy. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Matrix Solid‐phase Dispersion Extraction for Chromatographic Analysis of Labdane Diterpenoids in Coleus forskohlii
Authors: Yin Jiajun , Wang Yaqin , Tan Bo , Kang Yun , Xie Daotao , Tian Lulu , Huang Jianming
Published: July 2012

Introduction

The quality of Coleus forskohlii is often evaluated by high performance liquid chromatography (HPLC), using bioactive labdane diterpenoids as chemical markers. However, the existing sample preparation methods for the analysis of diterpenoids in C. forskohlii are generally labour‐intensive, time‐consuming and require large volumes of solvents.

Objective

To establish an efficient matrix solid‐phase dispersion (MSPD) extraction method for the simultaneous analysis of five bioactive diterpenoids in C. forskohlii by HPLC.

Methodology

Herbal samples were prepared by an optimised MSPD procedure using C18 as the sorbent. The quantification of the diterpenoids was achieved by HPLC with evaporative light scattering detector (ELSD), and the identification of the five compounds was performed by HPLC with tandem mass detector (MS/MS). The efficiency of the MSPD method was also compared with other extraction techniques including Soxhlet extraction, heat reflux extraction, ultrasonic‐assisted extraction and microwave‐assisted extraction.

Results

The MSPD extracted five diterpenoids with satisfactory recoveries ranging from 98.36% to 102.08%. Compared with other extraction methods, the proposed MSPD method had the advantages of combining extraction and clean‐up into a single step, consuming less time and requiring lower solvent volumes.

Conclusion

The MSPD method is simple, rapid and efficient for the extraction of labdane diterpenoids from C. forskohlii. The MSPD procedure coupled with HPLC–ELSD or HPLC–MS/MS is suitable for the quantification and identification of the diterpenoids in C. forskohlii. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3‐MSD cohort
Authors: Rossignol Michel , Begaud Bernard , Engel Pierre , Avouac Bernard , Lert France , Rouillon Frederic , Bénichou Jacques , Massol Jacques , Duru Gerard , Magnier Anne‐Marie , Guillemot Didier , Grimaldi‐Bensouda Lamiae , Abenhaim Lucien ,   for the EPI3‐LA‐SER group
Published: July 2012

Objective

The objective of this study was to assess the effect of physician practicing preferences (PPP) in primary care for homeopathy (Ho), CAM (Complementary and alternative medicines) with conventional medicine (Mx) or exclusively conventional medicine (CM) on patients with musculoskeletal disorders (MSDs), with reference to clinical progression, drug consumption, side effects and loss of therapeutic opportunity.

Methods

The EPI3‐MSD study was a nationwide observational cohort of a representative sample of general practitioners (GP) and their patients in France. Recruitment of GP was stratified by PPP, which was self‐declared. Diagnoses and comorbidities were recorded by GP at inclusion. Patients completed a standardized telephone interview at inclusion, one, three and twelve months, including MSD‐functional scales and medication consumption.

Results

1153 MSD patients were included in the three PPP groups. Patients did not differ between groups except for chronicity of MSDs (>12 weeks), which was higher in the Ho group (62.1%) than in the CM (48.6%) and Mx groups (50.3%). The twelve‐month development of specific functional scores was identical across the three groups after controlling for baseline score (p > 0.05). After adjusting for propensity scores, NSAID use over 12 months was almost half in the Ho group (OR, 0.54; 95%CI, 0.38–0.78) as compared to the CM group; no difference was found in the Mx group (OR, 0.81; 95% CI: 0.59–1.15).

Conclusion

MSD patients seen by homeopathic physicians showed a similar clinical progression when less exposed to NSAID in comparison to patients seen in CM practice, with fewer NSAID‐related adverse events and no loss of therapeutic opportunity. Copyright © 2012 John Wiley & Sons, Ltd.
Thermal expansion of Cu(II)O nano‐ and micro‐particles and composites at cryogenic temperatures
Authors: Neely Lauren A. , See Erich M. , Robinson Hans D. , Kochergin Vladimir
Published: July 2012

A systematic study of the thermal expansion of copper oxide (CuO) nanoparticles and copper oxide‐based composites, prepared by a range of techniques, was performed at cryogenic temperatures in the effort to reproduce recently reported giant negative coefficient of thermal expansion (CTE) of CuO nanoparticles. Chemically synthesized CuO nanoparticles, nanoparticles formed by ball milling of CuO material, CuO nanoparticles with differing surface functionalization, particles subjected to post‐treatments such as electron irradiation, and embedded into various resins or compacted at high pressures were studied by dilatometry and X‐ray diffraction (XRD) at temperatures between 20 and 300 K. None of the samples exhibited large negative CTE in the examined temperature range.
On the stability of elastic nanoparticles
Authors: Petrov M. I. , Melehin V. G. , Lipovskii A. A.
Published: July 2012

Recent studies aimed at modification and destruction of metal nanoparticles via laser pulse and DC electric field treatment require careful analyses of charge and field instability of metal nanoparticles. Though the stability bounds of liquid drops are known well, the stability conditions of rigid nanoparticle surrounded by elastic media are still not clear. In this work we have revealed the boundaries of charge and electric field stability for rigid nanoparticles.

magnified image

Charge‐field stability bounds of silver nanoparticle embedded in glass.
Plant Layout and Pick‐and‐place Strategies for Improving Performances in Secondary Packaging Plants of Food Products
Authors: Comba Lorenzo , Belforte Gustavo , Gay Paolo
Published: July 2012

The aim of secondary packaging plants is to pick food products from a conveyor belt and to place them into boxes. The typical configuration of these packaging plants consists of a set of sequential robot stations, performing pick‐and‐place cycles from one conveyor to another parallel one, which transport the products and the boxes to be filled. Depending on the relative movement of the two conveyors, the plant operates in co‐current or counter‐current flow configuration. Undesired perturbations in the product flow rate from its nominal value can lead to critical events, i.e. unpicked product at the end of the first conveyor or not completely filled boxes. Even if the structures of co‐current flow and of counter‐current flow plants are very similar, their behaviour in non‐nominal or perturbed conditions can significantly differ.

The aim of this paper is to deeply investigate the behaviour of these two kinds of secondary packaging lines, evaluating their performances in the case of different pick‐and‐place strategies, using discrete events simulation techniques.

Results show to which extent the different proposed control strategies can improve the performances of both co‐current and counter‐currents plants and, in particular, how co‐current plant layouts can achieve performances that are equivalent to, or perhaps even better than, those that can be obtained with a counter‐current plant layout, which cannot be freely used because of patent. The simulation tool, control algorithms and results presented can help packaging plant designers for choosing the most appropriate solutions and for properly sizing the plant. Copyright © 2012 John Wiley & Sons, Ltd.
The Lyapunov approach to boundary stabilization of an anti‐stable one‐dimensional wave equation with boundary disturbance
Authors: Guo Bao‐Zhu , Kang Wen
Published: July 2012

In this paper, we are concerned with the boundary stabilization of a one‐dimensional anti‐stable wave equation with the boundary external disturbance. The backstepping method is first applied to transform the anti‐stability from the free end to the control end. A variable structure feedback stabilizing controller is designed by the Lyapunov function approach. It is shown that the resulting closed‐loop system is associated with a nonlinear semigroup and is asymptotically stable. In addition, we show that this controller is robust to the external disturbance in the sense that the vibrating energy of the closed‐loop system is also convergent to zero as time goes to infinity in the presence of bounded deterministic disturbance at the control end. The existence and uniqueness of the solution are also developed by the Galerkin approximation scheme. Copyright © 2012 John Wiley & Sons, Ltd.
Quantitative detection of purines in biologically relevant films with TOF‐Secondary Ion Mass Spectrometry
Authors: Jackson Lauren M. , Hue Jonathan J. , Winograd Nicholas
Published: July 2012

In purine‐depleted environments, the de novo purine biosynthetic pathway is catalyzed to ultimately produce inosine monophosphate (IMP), a purine invisible using current optical microscopy methodology. These enzymes form a complex, termed the ‘purinosome,’ to replenish IMP levels. Before cellular chemical imaging may be applied to monitor the distributions and fluctuations in purine levels, it is necessary to develop a scheme to quantitatively detect purines. Here, IMP and other purines in biologically relevant matrices have been detected quantitatively. These methods provide a time‐of‐flight‐secondary ion mass spectrometry protocol using C60+ primary ions to determine the concentration of biomolecules in a cell, such as HeLa, at the nanomolar level. Copyright © 2012 John Wiley & Sons, Ltd.
Weighted logrank tests for interval censored data when assessment times depend on treatment
Authors: Fay Michael P. , Shih Joanna H.
Published: July 2012

We consider weighted logrank tests for interval censored data when assessment times may depend on treatment, and for each individual, we only use the two assessment times that bracket the event of interest. It is known that treating finite right endpoints as observed events can substantially inflate the type I error rate under assessment–treatment dependence (ATD), but the validity of several other implementations of weighted logrank tests (score tests, permutation tests, multiple imputation tests) has not been studied in this situation. With a bounded number of unique assessment times, the score test under the grouped continuous model retains the type I error rate asymptotically under ATD; however, although the approximate permutation test based on the permutation central limit theorem is not asymptotically valid under every ATD scenario, we show through simulation that in many ATD scenarios, it retains the type I error rate better than the score test. We show a case where the approximate permutation test retains the type I error rate when the exact permutation test does not. We study and modify the multiple imputation logrank tests of Huang, Lee, and Yu (2008, Statistics in Medicine, 27: 3217–3226), showing that the distribution of the rank‐like scores asymptotically does not depend on the assessment times. We show through simulations that our modifications of the multiple imputation logrank tests retain the type I error rate in all cases studied, even with ATD and a small number of individuals in each treatment group. Simulations were performed using the interval R package. Published 2012. This article is a US Government work and is in the public domain in the USA.
Assessing the consistency assumption by exploring treatment by covariate interactions in mixed treatment comparison meta‐analysis: individual patient‐level covariates versus aggregate trial‐level covariates
Authors: Donegan Sarah , Williamson Paula , D'Alessandro Umberto , Smith Catrin Tudur
Published: July 2012

Mixed treatment comparison (MTC) meta‐analysis allows several treatments to be compared in a single analysis while utilising direct and indirect evidence. Treatment by covariate interactions can be included in MTC models to explore how the covariate modifies the treatment effects. If interactions exist, the assumptions underlying MTCs may be invalidated. For conventional pair‐wise meta‐analysis, important benefits regarding the investigation of such interactions, gained from using individual patient data (IPD) rather than aggregate data (AD), have been described. We aim to compare IPD MTC models including patient‐level covariates with AD MTC models including study‐level covariates. IPD and AD random‐effects MTC models for dichotomous outcomes are specified. Three assumptions are made regarding the interactions (i.e. independent, exchangeable and common interactions). The models are applied to a dataset to compare four drugs for treating malaria (i.e. amodiaquine‐artesunate, dihydroartemisinin‐piperaquine (DHAPQ), artemether‐lumefantrine and chlorproguanil‐dapsone plus artesunate) using the outcome unadjusted treatment success at day 28. The treatment effects and regression coefficients for interactions from the IPD models were more precise than those from AD models. Using IPD, assuming independent or exchangeable interactions, the regression coefficient for chlorproguanil‐dapsone plus artesunate versus DHAPQ was statistically significant and assuming common interactions, the common coefficient was significant; whereas using AD, no coefficients were significant. Using IPD, DHAPQ was the best drug; whereas using AD, the best drug varied. Using AD models, there was no evidence that the consistency assumption was invalid; whereas, the assumption was questionable based on the IPD models. The AD analyses were misleading. Copyright © 2012 John Wiley & Sons, Ltd.
Tailoring sparse multivariable regression techniques for prognostic single‐nucleotide polymorphism signatures
Authors: Binder H. , Benner A. , Bullinger L. , Schumacher M.
Published: July 2012

When seeking prognostic information for patients, modern technologies provide a huge amount of genomic measurements as a starting point. For single‐nucleotide polymorphisms (SNPs), there may be more than one million covariates that need to be simultaneously considered with respect to a clinical endpoint. Although the underlying biological problem cannot be solved on the basis of clinical cohorts of only modest size, some important SNPs might still be identified. Sparse multivariable regression techniques have recently become available for automatically identifying prognostic molecular signatures that comprise relatively few covariates and provide reasonable prediction performance. For illustrating how such approaches can be adapted to the specific features of SNP data, we propose different variants of a componentwise likelihood‐based boosting approach. The latter links SNP measurements to a time‐to‐event endpoint by a regression model that is built up in a large number of steps. The variants allow for strategic choices in dealing with SNPs that differ in variance because of their variation in minor allele frequencies. In addition, we propose a heuristic that allows computationally efficient handling of millions of covariates, thus opening the door for incorporating SNP × treatment interactions. We illustrate this using data from patients with acute myeloid leukemia. We judge the resulting models according to prediction error curves and using resampling data sets. We obtain increased stability by moving interpretation from the SNP to the gene level. By considering these different aspects, we outline a more general strategy for linking SNP measurements to a time‐to‐event endpoint by means of sparse multivariable regression models. Copyright © 2012 John Wiley & Sons, Ltd.