bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective Cyanosilylation of Ketones with Amino Acid/BINAP/Ruthenium(II)‐Lithium Phenoxide Catalyst Systems
Authors: Uemura Masato , Kurono Nobuhito , Sakai Yusuke , Ohkuma Takeshi
Published: July 2012

Enantioselective reactions of simple ketones, α,α‐ and β,β‐dialkoxy ketones, and α‐alkoxy ketones with trimethylsilyl cyanide catalyzed by the bimetallic systems of amino acid/BINAP/ruthenium(II) complexes and lithium phenoxide have been studied [BINAP=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl]. The Ru(PhGly)2(BINAP)‐lithium phenoxide system showed high enantioselectivity for the reaction of acetophenone derivatives to afford the cyanated products in up to 90% ee [PhGly=phenylglycinate]. For the cyanosilylation of dialkoxy ketones and α‐alkoxy ketones, the Ru(t‐Leu)2(BINAP)‐lithium phenoxide system exhibited the best catalyst performance to produce the cyanohydrin derivatives in up to 99% ee and 98% ee, respectively [t‐Leu=tert‐leucinate]. The excellent catalytic activity resulted in complete conversion in the reaction with a substrate‐to‐catalyst molar ratio (S/C) of 10,000 in the best cases.
Photochemically Induced Silylacylations of Alkynes with Acylsilanes
Authors: Zhang Hui‐Jun , Becker Peter , Huang He , Pirwerdjan Ramona , Pan Fang‐Fang , Bolm Carsten
Published: July 2012

Visible light initiates the stereoselective formation of two new bonds, a CC and a CSi bond, during the addition of acylsilanes to alkynes. At room temperature this photochemically induced transformation can be applied for the preparation of chromone derivatives in a highly atom‐economic manner.
Synthesis and Antiproliferative Activity of Polysubstituted Tetrahydropyridine and Piperidin‐4‐one‐3‐carboxylate Derivatives
Authors: Aeluri Raghunath , Alla Manjula , Bommena Vittal Rao , Murthy Ramalinga , Jain Nishant
Published: July 2012

A highly atom‐economic one‐pot multicomponent synthesis of polysubstituted tetrahydropyridines (THPs) is described. The reaction of anilines, aromatic aldehydes, and β‐keto esters proceeds in the presence of catalytic amount of zirconium tetrachloride, and the products can be further converted to the corresponding piperidin‐4‐one‐3‐carboxylates under acidic conditions. The two sets of products were evaluated for their anticancer activity and some of these compounds, particularly the piperidin‐4‐one‐3‐carboxylates have significant anticancer activity.
Chirality Organization in Phenylenediamines Induced by a Nonpeptidic Reverse‐Turn
Authors: Moriuchi Toshiyuki , Ohmura Satoshi D. , Morita Kenji , Hirao Toshikazu
Published: July 2012

The introduction of amino acid moieties into phenylenediamine derivatives is demonstrated to induce chirality in the π‐conjugated backbones and results in the formation of a nonpeptidic reverse‐turn conformation through intramolecular hydrogen bonds. The formation of the intramolecular hydrogen bonds plays an important role in the stabilization of the phenylenediamine radical cation, as the chirality‐organized structure is preserved through the intramolecular hydrogen bonding. The designed phenylenediamines have luminescent switching properties based on the redox states of the phenylenediamine moieties.
Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds
Authors: Pandey Ganesh , Gaikwad Amrut L. , Gadre Smita R.
Published: July 2012

Designed scaffold dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate was synthesized in optically pure form by photoinduced one‐electron reductive β‐activation of an α,β‐unsaturated carbonyl moiety for stereoselective CC bond formation. Use of the morpholine derivative as a “chemical multitalent” isdemonstrated by its easy transformation to valuable heterocyclic building blocks such as methyl [(2R,3S)‐3‐hydroxy‐5‐oxopyrrolidin‐2‐yl]acetate, methyl [(2R,3S)‐3‐amino‐5‐oxotetrahydrofuran‐2‐yl]acetate, (3R,4S)‐4‐aminohexane‐1,3,6‐triol, and 2‐[(2R,3S)‐3‐aminotetrahydrofuran‐2‐yl]ethanol.
Synthesis of π‐Extended Coumarins and Evaluation of Their Precursors as Reactive Fluorescent Probes for Mercury Ions
Authors: Kim Inae , Kim Dokyoung , Sambasivan Sunderraman , Ahn Kyo Han
Published: July 2012

An efficient synthetic route to π‐extended coumarin derivatives and their precursors that contain amino substituents has been developed. The synthesis involves monosubstitution of 2,7‐dihydroxynaphthalene with dimethylamine through the Bucherer reaction. The extended coumarins emit at much longer wavelengths and with higher quantum yields relative to a related coumarin. Two vinyl ethers, precursors of the extended coumarins, were prepared and evaluated as reactive probes for Hg2+ ions. The vinyl ethers undergo hydrolysis promoted by Hg2+ ions to produce the extended coumarins at physiological pH (pH 7.4) and room temperature, which is accompanied by fluorescence in the “turn‐on” mode. The vinyl ethers do not respond to various other metal species. The extended coumarins and their precursors are versatile sensing platforms for Hg2+ ions, as well as for the development of related reaction‐based sensing systems.
Birth Timing and Behavioral Responsiveness Predict Individual Differences in the Mother–Infant Relationship and Infant Behavior During Weaning and Maternal Breeding
Authors: Vandeleest Jessica J. , Capitanio John P.
Published: July 2012

There is a great deal of variability in mother–infant interactions and infant behavior across the first year of life in rhesus monkeys. The current article has two specific aims: (1) to determine if birth timing predicts variability in the mother–infant relationship and infant behavior during weaning and maternal breeding, and (2) to identify predictors of infant behavior during a period of acute challenge, maternal breeding. Forty‐one mother–infant pairs were observed during weaning when infants were 4.5 months old, and 33 were followed through maternal breeding. Subjective ratings of 16 adjectives reflecting qualities of maternal attitude, mother–infant interactions, and infant attitude were factor analyzed to construct factors relating to the mother–infant relationship (Relaxed and Aggressive) and infant behavior (Positive Engagement and Distress). During weaning, late born infants were more Positively Engaged than peak born infants (ANOVA, P < 0.05); however, birth timing did not affect the mother–infant relationship factors Relaxed and Aggressive or the infant attitude factor Distress. During maternal breeding, early born infants had less Relaxed relationships with their mothers than peak or late born infants, higher Positive Engagement scores than peak or late born infants, and tended to have higher Distress scores than peak born infants (repeated‐measures ANOVA, P < 0.05). In addition, Distress scores were higher during maternal breeding than during the pre‐ and postbreeding phases. Finally, multiple regression (P < 0.05) indicated that while infant behavioral responsiveness predicted infant Positive Engagement during the acute challenge of maternal breeding, qualities of the mother–infant relationship predicted infant Distress. These data suggest that birth timing influences the patterns of mother–infant interactions during weaning and maternal breeding. Additionally, infant behavioral responsiveness and mother–infant relationship quality impact infant social engagement and affect expression, respectively. Am. J. Primatol. 74:734‐746, 2012. © 2012 Wiley Periodicals, Inc.
Palladium‐catalyzed carbonylative cyclization of 3‐bromoallyl alcohols leading to furan‐2(5H)‐ones
Authors: Lee Hye Kyung , Cho Chan Sik
Published: July 2012

3‐Bromoallyl alcohols are carbonylatively cyclized under carbon monoxide pressure in toluene in the presence of a catalytic amount of Pd(OAc)2 and PPh3 along with Na2CO3 to give furan‐2(5H)‐ones in good yields. Copyright © 2012 John Wiley & Sons, Ltd.
Organogermanium polymers prepared from s‐indacene and carbodiimide compounds
Authors: Dahrouch Mohamed , Diaz Enzo , Gatica Nicolas , Moreno Yanko , Chavez Ivonne , Manriquez Juan Manuel , Rivière Pierre , Rivière‐Baudet Monique , Gornitzka Heinz , Castel Annie
Published: July 2012

The synthesis of bis‐organogermanium compounds including s‐indacene structure was described and showed the formation of one type of trans isomer characterized by spectroscopic methods. In the same way, the digermyl‐s‐indacene dichlorides were prepared and structural characterizations confirmed the unique formation of trans isomers. These digermyl‐s‐indacene dichlorides were used as monomers in a polymerization reaction in order to prepare poly(germyl‐s‐indacenes) and poly(germyl‐s‐indacene carbodiimides). However, only the products obtained from tetraalkyl‐s‐indacene reached high molecular weight, probably due to a minor steric hindrance compared to the hexaalkyl‐s‐indacene. Thermal degradation only starts from 250°C for poly(germyl‐s‐indacene carbodiimides) and from 350°C for poly(germyl‐s‐indacenes). The structures of the first digermyl‐s‐indacene dichlorides were determined by X‐ray analysis, confirming that the chlorogermyl groups are located in trans positions. Copyright © 2012 John Wiley & Sons, Ltd.
Efficient salicylaldimine ligands for a palladium‐catalyzed Suzuki–Miyaura cross‐coupling reaction
Authors: Liu Feng‐Shou , Huang Ying‐Tang , Lu Chao , Shen Dong‐Sheng , Cheng Tao
Published: July 2012

A series of salicylaldimine ligands were designed to promote palladium‐catalyzed Suzuki–Miyaura cross‐coupling reaction. After a screening process, a ligand with a bulky 2,4‐di‐tert‐butyl substituent on the salicyaldehyde backbone and cyclohexylamine moiety was found to serve as a good combination for this reaction in aqueous solutions of DMF. The protocol demonstrated a significant advance in the efficiency of the cross‐coupling of aryl bromides and aryl chlorides with arylboronic acids to produce the desired biaryl products. Copyright © 2012 John Wiley & Sons, Ltd.
A pH‐controllable imprinted composite membrane for selective separation of podophyllotoxin and its analog
Authors: Cheng Huiling , Zhu Xiufang , Yang Shunxiang , Wu Yuxi , Cao Qiue , Ding Zhongtao
Published: July 2012

A molecularly imprinted composite membrane (MICM) with pH‐controllability and selectivity to podophyllotoxin (PPT) was prepared using a polyvinylidene fluoride (PVDF) microfiltration membrane as the support. The functional monomer is 1‐phenyl‐3‐methyl‐4‐methacryloyl‐5‐pyrazolone (PMMP), which is a new β‐diketone compound with enol/ketol tautomerization. In this study, imprinting parameters, including the amounts of functional monomer and cross‐linker, and immersion time of membrane in the imprinting solution, were optimized by equilibrium adsorption experiments. Pore structure and surface morphology of the optimal MICM (MICM2) was characterized. Finally, competitive permeability of PPT in the presence of its analog 4′‐demethylpodophyllotoxin (DMEP) was measured under the drive of concentration difference. The results reveal that the surface morphology and pore structure of MICM2 are structurally different from those of the control nonimprinted membrane. As a result, MICM2 could efficiently recognize PPT in a complex system due to a better structural matching and the interaction between the functional groups of MICM2 and PPT. However, the most interesting finding is its pH‐controllability. The membrane could switch the preference to either PPT or DMEP with the change of pH values in the sample solution. At pH values smaller than 8.4, it led to a faster transportation of PPT, while the situation reversed to DMEP at pH values greater than 8.4. This peculiar property would lead this imprinted membrane to have potential application in the separation and enrichment of PPT, and the new functional monomer PMMP exhibited an attractive application prospect in the functional material fields. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Identification of the Secondary Follicle Cycle of Hexi Cashmere Goat
Authors: He Yanyu , Cheng Lixiang , Wang Jiqing , Liu Xiu , Luo Yuzhu
Published: July 2012

This experiment conducted to identify a periodic change of ultrastructures of secondary follicle characteristics during a whole year, reveal the molecule regulation of growth of cashmere. A total of 10 cashmere goats of 1‐year old were studied. The paraffin section and ultrathin slices of skin were made each month in a whole year, observed, photographed, and analyzed under light microscope and transmission electron microscope after stained. Following the development of down fiber, the ultrastructures of secondary follicle of Hexi cashmere goat showed a periodic change within a year. There were five different periods during a down fiber cycle. It was observed that the stage of telogen, proanagen, anagen, procatagen, and catagen was in January and February, March and April, May to August, September and October, and November and December, respectively. The key change observed in secondary follicle under transmission electron microscope was inner root sheath. This study illustrated the five different stage of secondary follicle of Hexi Cashmere goat within a whole growth cycle, and has provided more detailed information about the research field of Hexi cashmere goat. Choosing the suitable time to harvest the cashmere may get the profit maximization. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
SciMAT: A new science mapping analysis software tool
Authors: Cobo M.J. , López‐Herrera A.G. , Herrera‐Viedma E. , Herrera F.
Published: July 2012

This article presents a new open‐source software tool, SciMAT, which performs science mapping analysis within a longitudinal framework. It provides different modules that help the analyst to carry out all the steps of the science mapping workflow. In addition, SciMAT presents three key features that are remarkable in respect to other science mapping software tools: (a) a powerful preprocessing module to clean the raw bibliographical data, (b) the use of bibliometric measures to study the impact of each studied element, and (c) a wizard to configure the analysis.
Learning a concept‐based document similarity measure
Authors: Huang Lan , Milne David , Frank Eibe , Witten Ian H.
Published: July 2012

Document similarity measures are crucial components of many text‐analysis tasks, including information retrieval, document classification, and document clustering. Conventional measures are brittle: They estimate the surface overlap between documents based on the words they mention and ignore deeper semantic connections. We propose a new measure that assesses similarity at both the lexical and semantic levels, and learns from human judgments how to combine them by using machine‐learning techniques. Experiments show that the new measure produces values for documents that are more consistent with people's judgments than people are with each other. We also use it to classify and cluster large document sets covering different genres and topics, and find that it improves both classification and clustering performance.
Tragwerksentwurf, Konstruktion und statische Berechnung des “Echolotes”
Authors: Feyerabend Manfred
Published: July 2012

Die Fachhochschule Koblenz präsentierte sich auf der BUGA 2011 in Koblenz mit dem “Echolot”, einem hölzernen Experimentalpavillon. Der freien und ungeordnet erscheinenden Form liegt ein ausgeklügeltes analytisches Konstruktionsprinzip zugrunde. Die Bearbeitung vom ersten Entwurf bis zur Visualisierung, statischen Berechnung und Erstellen der Ausführungszeichnungen erfolgte innerhalb einer durchgängigen digitalen Prozesskette.

Anfang dieses Jahres wurde das Bauwerk mit dem “Holzbaupreis Rheinland‐Pfalz 2011” ausgezeichnet.

Structural Design, Construction and Structural Analysis of the “Echolot”

During the National Garden Show “BUGA 2011” in Koblenz the Koblenz University of Applied Sciences presented the in‐house designed wooden experimental pavilion “Echolot”. Basis of the free and seemingly unorganized outer appearance of the pavilion was a sophisticated analytical structural concept. The complete working process, beginning with the first design‐drawings, including visualization and structural analysis and finally the shop drawings based on a consistent digital workflow.

The building was awarded with the “Holzbaupreis Rheinland‐Pfalz 2011” (the wooden structure award of Rhineland‐Palatinate 2011).
Effects of Transplacental 17‐α‐Ethynyl Estradiol or Bisphenol A on the Developmental Profile of Steroidogenic Acute Regulatory Protein in the Rat Testis
Authors: Horstman Karla A. , Naciff Jorge M. , Overmann Gary J. , Foertsch Leslie M. , Richardson Brian D. , Daston George P.
Published: July 2012

Previous research from our laboratory has determined the transcript profiles for developing fetal rat female and male reproductive tracts following transplacental exposure to estrogens. Prenatal exposure to bisphenol A (BPA) or 17‐α‐ethynyl estradiol (EE) significantly affects steroidogenic acute regulatory (StAR) protein transcript levels in the developing male rat reproductive tract. The purpose of this study was to establish the intratesticular distribution and temporal expression pattern of StAR, a key gene involved in steroidogenesis. Beginning on gestation day (GD) 11, pregnant Sprague‐Dawley rats were exposed daily to 10μg/kg/day EE and fetal testes were harvested at GD16, 18, or 20. Quantitative reverse transcriptase PCR (QRT‐PCR) demonstrated no significant difference in StAR transcript levels present at GD16. However, at GD18, StAR transcripts were significantly decreased following exposure. Immunohistochemistry demonstrated similar StAR protein levels in interstitial region of GD16 testes and an obvious decrease in StAR protein levels in the interstitial region of GD18 testes. Moreover, starting at GD11 additional dams were dosed with 0.001 or 0.1 μg/kg/day EE or 0.02, 0.5, 400 mg/kg/day BPA via subcutaneous injections. QRT‐PCR validated previous microarray dose‐related decreases in StAR transcripts at GD20, whereas immunohistochemistry results demonstrated decreases in StAR protein levels in the interstitial region at the highest EE and BPA doses only. Neither EE nor BPA exposure caused morphological changes in the developing seminiferous cords, Sertoli cells, gonocytes, or the interstitial region or Leydig cells at GD16–20. High levels of estrogens decrease StAR expression in the fetal rat testis during late gestation.
Erzielbare Detektionstiefen metallischer Reflektoren mit dem Impulsradarverfahren an Beton
Authors: Taffe Alexander , Feistkorn Sascha , Diersch Norman
Published: July 2012

Das Impulsradarverfahren hat sich in der zerstörungsfreien Prüfung im Bauwesen in den letzten Jahren etabliert. Mögliche Nutzer des Verfahrens sind oft daran interessiert, in einer ersten Abschätzung herauszufinden, ob Impulsradar bei ihrer Prüfaufgabe sinnvoll eingesetzt werden kann. Sofern die physikalischen Voraussetzungen für die Anwendbarkeit gegeben sind, ist danach die Machbarkeit von Interesse. Dazu ist die erzielbare Detektionstiefe von Bewehrungsstäben in Beton mit Radar von Bedeutung. In diesem Beitrag werden systematische Untersuchungen beschrieben, bei denen die erzielbare Detektionstiefe von Bewehrungsstäben in Betonbauteilen zunächst auf einfache Weise visuell quantifiziert wurde. Diese Untersuchungen wurden mit verschiedenen Antennenmittenfrequenzen durchgeführt. Dazu wurden Betonbauteile konzipiert, die bezüglich der Größen Einbautiefe, Bewehrung, Betonalter (Aushärtung des Betons) und Betonrezeptur variiert wurden. Am Ende stehen Kurven, aus denen die realistisch erzielbaren Detektionstiefen von Bewehrungsstäben in Beton in Abhängigkeit von Betonalter, Antennenmittenfrequenz und Betonsorte abgelesen werden können. Um den Einfluss der oberflächennahen Bewehrung und des Größtkorns der Gesteinskörnung auf die Detektionstiefen zu quantifizieren, sind tiefergehende Auswertungen mithilfe der POD(a)‐Analyse erforderlich. Die Ergebnisse dieser beiden Einflussgrößen sind als Teil einer umfangreichen Dissertation zum Thema POD hier dargestellt.

Quantification of depth measurement for the detection of metal rebars using Radar

Among non‐destructive testing methods in civil‐engineering (NDT‐CE) Radar or GPR (Ground Penetrating Radar) has been well established. As a first step the engineer has to make sure the chosen NDT‐method is applicable. When the physical requirements for an application are fulfilled the engineer wants to know up to what depth he might detect reinforcement bars. This article summarizes the results of systematic testing with radar at well‐defined test specimens with different concrete mixtures, rebars in various depths using different antenna frequencies for their detection. As a result simple detection curves allow the engineer to estimate the attainable detection depth of reinforcement bars depending on the concrete age, concrete mixture and antenna frequency. To quantify the influence of the reinforcement near the surface or the maximum grain size of the aggregate advanced data assessment using the theory of POD (Probability of Detection) is presented as part of a comprehensive PhD thesis.
Vergleich der rechnerischen Querkrafttragfähigkeit von Bestandsbrücken nach Eurocode 2 und fib Model Code 2010
Authors: Huber Patrick , Schweighofer Anton , Kollegger Johann , Brunner Helmut , Karigl Walter
Published: July 2012

Das ständig steigende Verkehrsaufkommen sowie die im Laufe der Jahre überarbeiteten Bemessungsnormen erfordern eine neue Beurteilung der angestrebten Nutzungsdauer bestehender Brücken. Die rechnerische Schubtragfähigkeit erweist sich hierbei in vielen Fällen als besonders problematisch. Im Zuge der Überarbeitung der österreichischen Nachrechnungsrichtlinie ONR 24008 “Bewertung der Tragfähigkeit bestehender Eisenbahn‐ und Straßenbrücken” wurden Vergleichsberechnungen bezüglich der rechnerischen Querkrafttragfähigkeit von Bestandsbrücken nach Eurocode 2 und fib Model Code 2010 durchgeführt. Der vorliegende Beitrag fasst die wesentlichen Ergebnisse aus dem Vergleich zwischen fib Model Code 2010 und dem Eurocode 2 zusammen und erläutert die Besonderheiten der Berechnung der rechnerischen Querkrafttragfähigkeit gemäß fib Model Code 2010.

Comparison of the calculative shear resistance of existing bridges according to Eurocode 2 and fib Model Code 2010

Due to the constantly increasing traffic loads and the revised design approaches it becomes necessary to reassess the expected service life of existing bridges. In many cases the calculative shear resistance turns out to be particularly problematic. In the course of the revision of the Austrian Assessment Technical Regulation ONR 24008 “Evaluation of load capacity of existing railway and highway bridges” comparative calculations according to the shear carrying capacity of existing bridges conforming to Eurocode 2 and fib Model Code 2010 were carried out. The present paper summarizes the main results of the comparison between the fib Model Code 2010 and Eurocode 2 and explains characteristics of the calculations of the shear resistance according to fib Model Code 2010.
The characterization and quantitation of glycomic changes in CHO cells during a bioreactor campaign
Authors: Tep Samnang , Hincapie Marina , Hancock William S.
Published: July 2012

Within the biotechnology industry there is a continuous drive to better and more fully understand the biopharmaceutical process in order to achieve better process control. A method to monitor and quantitate glycomic changes that occur in CHO cells during a bioreactor campaign could help to address this. The goal of the method presented here is to provide data that may help to understand the changes in glycosylation that are occurring, within the cell, to proteins other than the expressed biotherapeutic. The method involves the lysing of cells to gain access to intracellular proteins. The expressed biotherapeutic is specifically removed by affinity chromatography, while the remaining proteins are subjected to deglycosylation by treatment with PNGase F. The released glycans are derivatized with isotopic tags, and quantitative analysis by MALDI‐TOF MS is performed. The MALDI‐TOF MS method allows for the simultaneous analysis of both neutral and sialylated glycans, displays a linear dynamic range over two orders of magnitude for both neutral and sialylated glycans and achieves sub‐picomolar sensitivity. This method may yield valuable information that gives further insight into the inner‐workings of CHO cells, potentially taking another step towards fully understanding and controlling the biopharmaceutical process. Biotechnol. Bioeng. 2012; 109: 3007–3017. © 2012 Wiley Periodicals, Inc.
A genetic and metabolic approach to redirection of biochemical pathways of Clostridium butyricum for enhancing hydrogen production
Authors: Cai Guiqin , Jin Bo , Monis Paul , Saint Christopher
Published: July 2012

Clostridium butyricum, a well known H2 producing bacterium, produces lactate, butyrate, acetate, ethanol, and CO2 as its main by‐products from glucose. The conversion of pyruvate to lactate, butyrate and ethanol involves oxidation of NADH. It was hypothesized that the NADH could be increased if the formation of these by‐products could be eliminated, resulting in enhancing H2 yield. Herein, this study aimed to establish a genetic and metabolic approach for enhancing H2 yield via redirection of metabolic pathways of a C. butyricum strain. The ethanol formation pathway was blocked by disruption of aad (encoding aldehyde‐alcohol dehydrogenase) using a ClosTron plasmid. Although elimination of ethanol formation alone did not increase hydrogen production, the resulting aad‐deficient mutant showed approximately 20% enhanced performance in hydrogen production with the addition of sodium acetate. This work demonstrated the possibility of improving hydrogen yield by eliminating the unfavorable by‐products ethanol and lactate. Biotechnol. Bioeng. 2013; 110: 338–342. © 2012 Wiley Periodicals, Inc.
Arginine functionalization of hydrogels for heparin binding—a supramolecular approach to developing a pro‐angiogenic biomaterial
Authors: Gilmore Louisa , Rimmer Stephen , McArthur Sally L. , Mittar Shweta , Sun Dachau , MacNeil Sheila
Published: July 2012

Our aim was to synthesize a biomaterial that stimulates angiogenesis for tissue engineering applications by exploiting the ability of heparin to bind and release vascular endothelial growth factor (VEGF). The approach adopted involved modification of a hydrogel with positively charged peptides (oligolysine or oligoarginine) to achieve heparin binding. Precursor hydrogels were produced from copolymerization of N‐vinyl pyrolidone, diethylene glycol bis allyl carbonate and acrylic acid (PNDA) and functionalized after activation of the carboxylic acid groups with trilysine or triarginine peptides (PNDKKK and PNDRRR). Both hydrogels were shown to bind and release bioactive VEGF165 with arginine‐modified hydrogel outperforming the lysine‐modified hydrogel. Cytocompatibility of the hydrogels was confirmed in vitro with primary human dermal fibroblasts and human dermal microvascular endothelial cells (HUDMECs). Proliferation of HUDMECs was stimulated by triarginine‐functionalized hydrogels, and to a lesser extent by lysine functionalized hydrogels once loaded with heparin and VEGF. The data suggests that heparin‐binding hydrogels provide a promising approach to a pro‐angiogenic biomaterial. Biotechnol. Bioeng. 2013; 110: 296–317. © 2012 Wiley Periodicals, Inc.
Optimized keyframe extraction for 3D character animations
Authors: Jin Chao , Fevens Thomas , Mudur Sudhir
Published: July 2012

In this paper, we propose a new method to automatically extract keyframes from animation sequences. Our method can be applied equally to both skeletal and mesh animations. It uses animation saliency computed on the original data to help select the group of keyframes that can reconstruct the input animation with less perception error. For computational efficiency, we perform nonlinear dimension reduction using locally linear embedding and then carry out the optimal search in much lower‐dimensional space. With this approach, reconstruction of the animation from the extracted keyframes shows much better results as compared with earlier approaches. Copyright © 2012 John Wiley & Sons, Ltd.
[NiCl2(dppp)]‐Catalyzed Cross‐Coupling of Aryl Halides with Dialkyl Phosphite, Diphenylphosphine Oxide, and Diphenylphosphine
Authors: Zhao Yu‐Long , Wu Guo‐Jie , Li You , Gao Lian‐Xun , Han Fu‐She
Published: July 2012

We present a general approach to CP bond formation through the cross‐coupling of aryl halides with a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane by using [NiCl2(dppp)] as catalyst (dppp=1,3‐bis(diphenylphosphino)propane). This catalyst system displays a broad applicability that is capable of catalyzing the cross‐coupling of aryl bromides, particularly a range of unreactive aryl chlorides, with various types of phosphorus substrates, such as a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane. Consequently, the synthesis of valuable phosphonates, phosphine oxides, and phosphanes can be achieved with one catalyst system. Moreover, the reaction proceeds not only at a much lower temperature (100–120 °C) relative to the classic Arbuzov reaction (ca. 160–220 °C), but also without the need of external reductants and supporting ligands. In addition, owing to the relatively mild reaction conditions, a range of labile groups, such as ether, ester, ketone, and cyano groups, are tolerated. Finally, a brief mechanistic study revealed that by using [NiCl2(dppp)] as a catalyst, the NiII center could be readily reduced in situ to Ni0 by the phosphorus substrates due to the influence of the dppp ligand, thereby facilitating the oxidative addition of aryl halides to a Ni0 center. This step is the key to bringing the reaction into the catalytic cycle.
FMO‐MD Simulations on the Hydration of Formaldehyde in Water Solution with Constraint Dynamics
Authors: Sato Makoto , Yamataka Hiroshi , Komeiji Yuto , Mochizuki Yuji
Published: July 2012

Full‐quantum mechanical fragment molecular orbital‐based molecular dynamics (FMO‐MD) simulations were applied to the hydration reaction of formaldehyde in water solution under neutral conditions. Two mechanisms, a concerted and a stepwise one, were considered with respect to the nucleophilic addition and the proton transfer. Preliminary molecular orbital calculations by means of polarized continuum model reaction field predicted that the hydration prefers a concerted mechanism. Because the calculated activation barriers were too high for free FMO‐MD simulations to give reactive trajectories spontaneously, a More O’Ferrall–Jencks‐type diagram was constructed from the statistical analysis of the FMO‐MD simulations with constraint dynamics. The diagram showed that the hydration proceeds through a zwitterionic‐like (ZW‐like) structure. The free energy changes along the reaction coordinate calculated by means of the blue moon ensemble for the hydration and the amination of formaldehyde indicated that the hydration proceeds through a concerted process through the ZW‐like structure, whereas the amination goes through a stepwise mechanism with a ZW intermediate. In inspection of the FMO‐MD trajectories, water‐mediated cyclic proton transfers were observed in both reactions on the way from the ZW‐like structure to the product. These proton transfers also have an asynchronous character, in which deprotonation from the nucleophilic oxygen atom (or nitrogen atom for amination) precedes the protonation of the carbonyl oxygen atom. The results showed the strong advantage of the FMO‐MD simulations to obtain detailed information at a molecular level for solution reactions.
Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long‐term enhancement of adult defensive behaviors
Authors: Wright Lisa D. , Muir Katherine E. , Perrot Tara S.
Published: July 2012

In order to characterize the short‐ and long‐term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38–46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth‐exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress‐induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety‐like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long‐term outcomes. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 551–567, 2013
Inbreeding rate modifies the dynamics of genetic load in small populations
Authors: Pekkala Nina , Emily Knott K. , Kotiaho Janne S. , Puurtinen Mikael
Published: July 2012

The negative fitness consequences of close inbreeding are widely recognized, but predicting the long‐term effects of inbreeding and genetic drift due to limited population size is not straightforward. As the frequency and homozygosity of recessive deleterious alleles increase, selection can remove (purge) them from a population, reducing the genetic load. At the same time, small population size relaxes selection against mildly harmful mutations, which may lead to accumulation of genetic load. The efficiency of purging and the accumulation of mutations both depend on the rate of inbreeding (i.e., population size) and on the nature of mutations. We studied how increasing levels of inbreeding affect offspring production and extinction in experimental Drosophila littoralis populations replicated in two sizes, N = 10 and N = 40. Offspring production and extinction were measured over 25 generations concurrently with a large control population. In the N = 10 populations, offspring production decreased strongly at low levels of inbreeding, then recovered only to show a consistent subsequent decline, suggesting early expression and purging of recessive highly deleterious alleles and subsequent accumulation of mildly harmful mutations. In the N = 40 populations, offspring production declined only after inbreeding reached higher levels, suggesting that inbreeding and genetic drift pose a smaller threat to population fitness when inbreeding is slow. Our results suggest that highly deleterious alleles can be purged in small populations already at low levels of inbreeding, but that purging does not protect the small populations from eventual genetic deterioration and extinction.
Phylogenetic assessment of filoviruses: how many lineages ofMarburg virus?
Authors: Peterson A. Townsend , Holder Mark T.
Published: July 2012

Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available for theFiloviridae: using coalescent simulations, we ascertain that two Marburg isolates (termed the “RAVN” strain) represent a quite‐distinct lineage that should be considered in studies of biogeography and host associations, and may merit recognition at the level of species. In contrast, filovirus isolates recently obtained from bat tissues are not distinct from previously known strains, and should be considered as drawn from the same population. Implications for understanding the transmission geography and host associations of these viruses are discussed.
Comparison Versus Contrast: Task Specifics Affect Category Acquisition
Authors: Ankowski Amber A. , Vlach Haley A. , Sandhofer Catherine M.
Published: July 2012

A large literature has documented that comparison and contrast lead to better performance in a variety of tasks. However, studies of comparison and contrast present contradictory conclusions as to when and how these processes benefit learners. Across four studies, we examined how the specifics of the comparison and contrast task affect performance by systematically manipulating the feature variation and category structure in a category extension task performed by 3‐year‐old and 4‐year‐old children. Studies 1 (n = 48, M = 42.6 months) and 2 (n = 48, M = 42. 4 months) investigated comparison and contrast with high‐density categories. Studies 3A (n = 60, M = 43.47 months), 3B (n = 48, M = 53. 2 months) and 4 (n = 48, M = 53.7 months) investigated comparison and contrast with low‐density categories. Results indicated both category structure and feature variation affect the efficacy of comparison and contrast. Copyright © 2012 John Wiley & Sons, Ltd.
Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer
Authors: Auvinen Päivi , Tammi Raija , Kosma Veli‐Matti , Sironen Reijo , Soini Ylermi , Mannermaa Arto , Tumelius Ritva , Uljas Eliisa , Tammi Markku
Published: July 2012

Previous in vitro studies have suggested interactions between hyaluronan (HA), CD44 and HER2. We have studied the expression of HA and CD44 in a material of 278 breast cancer cases, half of which were HER2‐positive. Intense stromal HA staining was associated with HER2 positivity, large tumor size, lymph node positivity, hormone receptor negativity, poor differentiation, a high body mass index, increased relapse rate and shortened overall survival. Among the 139 HER2‐positive cases, the relapse rate was associated with the intensity of stromal HA staining as most of the relapses occurred in the cases with intense stromal HA staining. The presence of HA in the carcinoma cells was related to the frequency of relapses as none of the patients without HA in carcinoma cells experienced a relapse, whereas 33.3% of those with a high percentage of HA‐positive carcinoma cells suffered a relapse. CD44 positivity in carcinoma cells was related to poor differentiation, postmenopausal status and triple negative breast carcinoma. CD44 positivity in stromal cells was associated with HER2 positivity, large tumor size, hormone receptor negativity, poor differentiation, increased relapse rate and shortened overall survival. The association between HER2 positivity and intense stromal HA staining indicates that HA could be one of the factors involved in the unfavorable outcome of HER2‐positive patients. This study also suggests that HA in breast carcinoma cells and CD44 in stromal cells may have clinical significance.
ZEB/miR‐200 feedback loop: At the crossroads of signal transduction in cancer
Authors: Hill Louise , Browne Gareth , Tulchinsky Eugene
Published: July 2012

Embryonic differentiation programs of epithelial–mesenchymal and mesenchymal–epithelial transition (EMT and MET) represent a mechanistic basis for epithelial cell plasticity implicated in cancer. Transcription factors of the ZEB protein family (ZEB1 and ZEB2) and several microRNA species (predominantly miR‐200 family members) form a double negative feedback loop, which controls EMT and MET programs in both development and tumorigenesis. In this article, we review crosstalk between the ZEB/miR‐200 axis and several signal transduction pathways activated at different stages of tumor development. The close association of ZEB proteins with these pathways is indirect evidence for the involvement of a ZEB/miR‐200 loop in tumor initiation, progression and spread. Additionally, the configuration of signaling pathways involving ZEB/miR‐200 loop suggests that ZEB1 and ZEB2 may have different, possibly even opposing, roles in some forms of human cancer.
Functional characterization of the novel BRAF complex mutation, BRAFV600delinsYM, identified in papillary thyroid carcinoma
Authors: Matsuse Michiko , Mitsutake Norisato , Tanimura Susumu , Ogi Tomoo , Nishihara Eijun , Hirokawa Mitsuyoshi , Fuziwara Cesar S. , Saenko Vladimir A. , Suzuki Keiji , Miyauchi Akira , Yamashita Shunichi
Published: July 2012

An activating mutation in the BRAF gene is the most common genetic alteration in papillary thyroid carcinomas (PTCs). The mutation in PTCs is almost a c.1799T>A transversion, resulting in a p.V600E amino acid substitution (BRAFV600E). Here, we report a novel complex BRAF mutation identified in 4/492 Japanese PTC cases (0.81%). The mutation was comprised of one nucleotide substitution at position 1798, followed by an in‐frame insertion of three nucleotides, c.1798delinsTACA in Exon 15, resulting in p.V600delinsYM. In silico three‐dimensional protein structure prediction implied altered kinase activity of this mutant. In vitro kinase assay and western blotting revealed that this mutation conferred high kinase activity on the BRAF protein, leading to constitutive activation of the MAPK signaling pathway. The mutation also showed high transforming ability in focus formation assay using NIH3T3 cells. The degree of all the functional characteristics was comparable to that of BRAFV600E, and treatment with a BRAF inhibitor Sorafenib was also equally effective in this mutant. These findings suggest that the novel BRAF mutation, BRAFV600delinsYM, is a gain‐of‐function mutation and plays an important role in PTC development.
Silencing IDO in dendritic cells: A novel approach to enhance cancer immunotherapy in a murine breast cancer model
Authors: Zheng Xiufen , Koropatnick James , Chen Di , Velenosi Thomas , Ling Hong , Zhang Xusheng , Jiang Nan , Navarro Benjamin , Ichim Thomas E. , Urquhart Bradley , Min Weiping
Published: July 2012

Cancer immunotherapeutic agents (vaccines) in the form of antigen‐loaded dendritic cells (DCs) reached an important milestone with the recent approval of Provenge, the first DC vaccine for treatment of prostate cancer. Although this heralds a new era of tumor immunotherapy, it also highlights the compelling need to optimize such DC‐based therapies as they are increasingly tested and used to treat human patients. In this study we sought to augment and enhance the antitumor activity of a DC‐based vaccine using siRNA to silence expression of immunosuppressive enzyme indoleamine 2,3‐dioxygenase (IDO) in DCs. We report here that DCs loaded with tumor antigens, but with siRNA‐silenced IDO expression, were introduced into 4T1 breast tumor‐bearing mice, the treatment: (i) lengthened the time required for tumor onset, (ii) decreased tumor size compared to tumors grown for equal lengths of time in mice treated with antigen‐loaded DCs without IDO silencing and (iii) reduced CD4+ and CD8+ T cell apoptosis. Furthermore, immunization with IDO‐silenced DCs enhanced tumor antigen‐specific T cell proliferation and CTL activity, and decreased numbers of CD4+CD25+Foxp3+
Treg. This study provides evidence to support silencing of immunosuppressive genes (IDO) as an effective strategy to enhance the efficacy of DC‐based cancer immunotherapeutic.
Development of disruptive behaviors in young children: A prospective population‐based cohort study
Authors: Baillargeon Raymond H. , Morisset Alexandre , Keenan Kate , Normand Claude L. , Séguin Jean R. , Japel Christa , Cao Guanqiong
Published: July 2012

We know relatively little about the development of disruptive behaviors (DBs), and gender differences therein. The objective of this study was to describe the continuity and discontinuity in the degree to which young children in the general population are reported to exhibit specific DBs over time. Data came from the Québec Longitudinal Study of Child Development. First, the results show that relatively few children exhibit DBs on a frequent basis at 41 months of age. Second, the results show that a majority of children who exhibit a particular DB on a frequent basis at 41 months of age did not do so 1 year earlier. In addition, a majority of children who exhibited a particular DB on a frequent basis at 29 months of age no longer do so 1 year later. Third, gender differences in DBs (boys > girls) are either emerging or at least increasing in magnitude between 29 and 41 months of age. Consistent with the canalization of the behavioral development principle, children who exhibited DBs on a frequent basis at 29 months of age are less likely to stop doing so in the following year if they had exhibited the same behaviors at 17 months of age.
Contextual factors associated with pain response of preterm infants to heel‐stick procedures
Authors: Sellam G. , Engberg S. , Denhaerynck K. , Craig K.D. , Cignacco E.L.
Published: July 2012

Background

Evidence indicates that medical and demographic contextual factors (cFs) impact pain responses in preterm neonates, but the existing evidence is very heterogeneous.

Aim

To explore the effect of cFs on pain responses to heel‐stick procedures of preterm infants.

Methods

This study was a secondary analysis of data collected during a randomized controlled trial examining pain response to non‐pharmacological interventions across repeated heel sticks. Five heel sticks across the first 14 days of life were videotaped. Pain response was rated with the Bernese Pain Scale for Neonates (BPSN) by four raters blinded to the heel‐stick phases (baseline, heel stick, recovery). Demographic and medical cFs were extracted from medical charts. Mixed single and multiple regression analyses were performed controlling for the intervention group, site and heel‐stick phase.

Results

Apgar scores at 1 min were negatively associated with behavioural (p = 0.002) BPSN scores, while Apgar scores at 5 min after birth were positively associated with behavioural (p = 0.006) scores. Accumulated number of painful procedures (p = 0.002) and gender (p = 0.02) were positively associated with physiological scores while continuous positive airway pressure CPAP (p = 0.009) and mechanical ventilation (p = 0.005) were negatively associated.

Conclusion

Higher exposure to painful procedures, male infants and having CPAP or mechanical ventilation were cFs associated with physiological response. The only variables significantly associated with behavioural BPSN scores were Apgar scores but these relationships were inconsistent.