bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling clinical development of an HIV attachment inhibitor through innovative pharmaceutical development: novel extended‐release delivery of prodrug
Authors: Brown J , Tobyn M , Brown S , Connolly T , Dennis A , Hanna G , Hughes H , Kadow J , Meanwell N , Wang T , Yeung K , Zhu L , Timmins P
Published: April 2013

Background

HIV‐1 attachment inhibitors are a new class of viral entry inhibitors which target viral gp120 preventing attachment of virus to its host cell receptor CD4. This class presents major challenges for development based upon low solubility and short half‐lives. For progression into clinical studies, requirements include reliable and reproducible absorption from a tolerable and convenient oral dosing regimen.

Methods

A series of highly soluble prodrugs were designed to overcome the poor absorption caused by the low solubility of the active compounds. A regional absorption study was conducted to assess the uptake of active throughout the gastro‐intestinal tract following oral prodrug delivery. An extended‐release (ER) strategy was subsequently devised to optimise tolerability, decrease peak to trough ratios and reduce frequency of dosing. In silico absorption modelling was used to verify feasibility and drive in vitro testing leading to dosage form development and selection. The performance of the ER dosage form was verified in vivo prior to use in clinical studies.

Results

Phosphonooxymethyl prodrugs with aqueous solubilities in excess of 250 mg/mL were synthesised and shown to be readily converted to parent compound via alkaline phosphatase in vitro. Results of regional absorption studies for the selected compound, BMS‐663068, confirmed the rapid absorption but short half‐life of active following oral administration of prodrug. Delivery to specific regions throughout the GI tract showed absorption of active to be subject to regional variation with an extent of colonic absorption of approximately 40% of intestinal absorption. Incorporation of this data into an in silico model guided development of an ER tablet which releases prodrug over 24 hours and achieves the required exposure, pharmacokinetics and reproducibility in vivo.

Conclusions

The novel approach of combining prodrug synthesis and ER formulation has enabled clinical evaluation of a promising new class of therapeutic entity into Phase 2b studies.
Considering the role of social dynamics and positional behavior in gestural communication research
Authors: Smith Lindsey W. , Delgado Roberto A.
Published: April 2013

While the hominin fossil record cannot inform us on either the presence or extent of social and cognitive abilities that may have paved the way for the emergence of language, studying non‐vocal communication among our closest living relatives, the African apes, may provide valuable information about how language originated. Although much has been learned from gestural signaling in non‐human primates, we have not yet established how and why gestural repertoires vary across species, what factors influence this variation, and how knowledge of these differences can contribute to an understanding of gestural signaling's contribution to language evolution. In this paper, we review arguments surrounding the theory that language evolved from gestural signaling and suggest some important factors to consider when conducting comparative studies of gestural communication among African apes. Specifically, we propose that social dynamics and positional behavior are critical components that shape the frequency and nature of gestural signaling across species and we argue that an understanding of these factors could shed light on how gestural communication may have been the basis of human language. We outline predictions for the influence of these factors on the frequencies and types of gestures used across the African apes and highlight the importance of including these factors in future gestural communication research with primates. Am. J. Primatol. 75:891–903, 2013. © 2013 Wiley Periodicals, Inc.
Structurally Defined Allyl Compounds of Main Group Metals: Coordination and Reactivity
Authors: Lichtenberg Crispin , Okuda Jun
Published: April 2013

Organometallic allyl compounds are important as allylation reagents in organic synthesis, as polymerization catalysts, and as volatile metal precursors in material science. Whereas the allyl chemistry of synthetically relevant transition metals such as palladium and of the lanthanoids is well‐established, that of main group metals has been lagging behind. Recent progress on allyl complexes of Groups 1, 2, and 12–16 now provides a more complete picture. This is based on a fundamental understanding of metal–allyl bonding interactions in solution and in the solid state. Furthermore, reactivity trends have been rationalized and new types of allyl‐specific reactivity patterns have been uncovered. Key features include 1) the exploitation of the different types of metal–allyl bonding (highly ionic to predominantly covalent), 2) the use of synergistic effects in heterobimetallic compounds, and 3) the adjustment of Lewis acidity by variation of the charge of allyl compounds.
Nonuniformity behavior during regeneration of the diesel particulate filter
Authors: Chen K. , Sun T.
Published: April 2013

The incomplete regeneration of diesel particulate filter may cause a local build‐up of the soot on the partially regenerated areas during next filtration cycle. This may be one of reasons causing the melting of the ceramic filter during regeneration. In this paper, we investigated several situations at which the particulate matter was partially regenerated. The simulations illustrated that at stationary feed conditions, the influence of nonuniformity of soot loading on the peak temperature rise was less important. When regeneration was conducted at transient feed conditions, the peak temperature attained under the condition of uneven soot distribution along the channel, especially more soot accumulated near the end of the diesel particulate filter, was much higher than that attained under the condition of even soot distribution inside the channel. © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
Bulk density of polymer solid granules in vane cylinder
Authors: Qu Jin Ping , Zhai Shu Feng , Liu Huan Yu , Chen Hui Zhuo , Jia Shi Kui , Huang Zan , Zhao Yong Qing , Liu Li Ming
Published: April 2013

Polymer granules are conveyed and plasticized using an innovational vane extruder composed of several vane plasticizing and conveying units (VPCUs). This study developed a mathematic model to analyze the bulk density of polymer granules in a VPCU, as well as conducted an experiment to investigate the effects of device geometry, polymer properties, and operating conditions on the model. By comparing the theoretical model data with the experiment data, the proposed model of bulk density is found to be aligned with actual conditions, thus providing a basis for device and process optimization. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 842‐850, 2013
Characteristics of diether‐ and phthalate‐based Ziegler‐Natta catalysts for copolymerization of propylene and ethylene and terpolymerization of propylene, ethylene, and 1‐butene
Authors: Song Bo Geun , Choi Young Heon , Ihm Son‐Ki
Published: April 2013

Copolymerization of propylene and ethylene and terpolymerization of propylene, ethylene, and 1‐butene were carried out to compare the characteristics of diether‐ and phthalate‐based Ziegler‐Natta catalysts in a reaction system of pilot scale. The ethylene incorporation with the diether‐based catalyst was higher but the 1‐butene incorporation was lower compared with those of the phthalate‐based catalyst. In the case of copolymers from the diether‐based catalyst, melting behavior, determined through differential scanning calorimetry (DSC), showed a distinct shoulder peak and lots of nuclei were formed during crystallization. The diether‐based catalyst led to polymers having blockier ethylene sequences compared with those of the phthalate‐based catalyst; the highly crystallizable fraction (HIS) containing blockier ethylene sequences was produced with the diether‐based catalyst. These results seem to be the result of regio‐irregular characteristics of the diether‐based catalyst. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 851‐859, 2013
Structure–Property Investigations of Substituted Triarylamines and Their Applications as Fluorescent pH Sensors
Authors: Hu Binbin , Chen Xiaopeng , Wang Yifei , Lu Ping , Wang Yanguang
Published: April 2013

Fourteen triphenylamine derivatives functionalized with fluorophenyl, methoxyphenyl, and pyridinyl groups as respective donors and acceptors were synthesized and characterized. Their photophysical properties were systematically investigated in various solvents with different polarities. The solvent‐dependent Stokes shifts of these compounds were observed and analyzed by the Lippert–Mataga equation. The synthesized compounds, especially tris(4‐(pyridin‐4‐yl)phenyl) amine, presented pH‐dependent absorptions and emissions, indicating that these compounds might be used as pH sensors.
Bright, Fluorescent Dyes Based on Imidazo[1,2‐a]pyridines that are Capable of Two‐Photon Absorption
Authors: Firmansyah Dikhi , Ciuciu Adina I. , Hugues Vincent , Blanchard‐Desce Mireille , Flamigni Lucia , Gryko Daniel T.
Published: April 2013

A library of imidazo[1,2‐a]pyridines was synthesized by using the Gevorgyan method and their linear and non‐linear optical properties were studied. Derivatives that contained both electron‐donating and electron‐withdrawing groups at the 2 position were comprehensively investigated. Their emission quantum yield ranged between 0.2–0.7 and it was shown to depend on the substitution pattern, most notably that on the phenyl ring. Electron‐donating substituents improved the luminescence performance of these compounds, whereas electron‐withdrawing substituents led to a more erratic behavior. Substitution on the six‐membered ring had less effect on the fluorescence properties. Extension of the delocalization increased the luminescence quantum yield. A new quadrupolar system was designed that contained two imidazo[1,2‐a]pyridine units on its periphery and a 1,4‐dicyanobenzene unit at its center. This system exhibited a large Stokes‐shifted luminescence that was affected by the polarity and rigidity of the solvent, which was ascribed to emission from an excited state with strong charge‐transfer character. This quadrupolar feature also led to an acceptable two‐photon absorption response in the NIR region.
Regulation of HA14‐1 mediated oxidative stress, toxic response, and autophagy by curcumin to enhance apoptotic activity in human embryonic kidney cells
Authors: Ranjan Kishu , Sharma Anupama , Surolia Avadhesha , Pathak Chandramani
Published: April 2013

An alteration in susceptibility to apoptosis not only contributes to promotion of malignancy but can also enhance drug resistance in response to anticancer therapies. HA14‐1 is a small molecule which has the potential of inducing apoptosis in cancerous cells. HA14‐1 manifests an antagonistic effect on antiapoptotic protein Bcl‐2 and consequently induces cell death in various cancerous cell lines. However, it is also known to generate ROS and toxic response in the cells upon decomposition. Elevated level of ROS is responsible for oxidative stress and other pathological consequences, if not metabolized properly. The aim of the present study was to examine the synergistic effect of curcumin in promoting apoptosis by regulating the HA14‐1 mediated ROS generation, toxicity, oxidative stress, and autophagy in human embryonic kidney cells. Our study demonstrates that curcumin efficiently scavenges HA14‐1 mediated generation of ROS and toxic response resulting in augmentation of apoptosis in HEK 293T cells by promoting inhibition of antiapoptotic proteins and process of autophagy. Thus curcumin along with HA14‐1 regulates cell proliferation by disruption of the antiapoptotic signaling mechanism. This approach could serve as a promising strategy for therapeutic potential to overcome their adverse effects. © 2013 BioFactors, 40(1):157–169, 2014
Confinement of Chemisorbed Phosphates in a Controlled Nanospace with Three‐Dimensional Mesostructures
Authors: Yang Jie , Zhou Liang , Zhang Jun , Zou Jin , Yuan Zhiguo , Yu Chengzhong
Published: April 2013

The confinement of phosphates inside adsorbents is important for not only entrophication control, but also the recovery of phosphorous, a depleting natural resource. However, the behaviour of chemisorbed phosphates inside nanoporous materials has not been systematically studied. Here, the confinement of chemisorbed phosphates in a three‐dimensional cubic mesoporous material with adjustable structural parameters is systematically investigated. By taking advantage of advanced electron tomography techniques, the relationship between the growth of chemisorbed phosphates, the overall phosphate‐adsorption performance and the mesostructural parameters is revealed. Cubic cage‐type FDU‐12 materials with tuneable entrance sizes were prepared and functionalised with different amounts of lanthanum oxide. When the entrance size is smaller than approximately 5 nm, phosphates are found only in isolated cages, thereby leading to low lanthanum (La) usage efficiency and phosphate removal capacity. When the entrance size is increased, chemisorption occurs in both cages and entrances, thus forming crystalline LaPO4 nanorods and increasing both the La usage efficiency and the phosphate removal capacity. In addition, the LaPO4 nanorods show a preferential orientation along the [110] direction. This study provides new insights in the rational design of phosphate adsorbents with controlled structures and high performance.
Comparative effectiveness of three platinum‐doublet chemotherapy regimens in elderly patients with advanced non–small cell lung cancer
Authors: Zhu Junya , Sharma Dhruv B. , Chen Aileen B. , Johnson Bruce E. , Weeks Jane C. , Schrag Deborah
Published: April 2013

BACKGROUND

Randomized trials report equivalent efficacy among various combinations of platinum‐based regimens in advanced non–small cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain.

METHODS

The authors used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked data to identify first‐line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to 2007. Overall survival was compared between patients who received the 3 most common regimens: carboplatin‐paclitaxel, carboplatin‐gemcitabine, and carboplatin‐docetaxel. Stratified analyses distinguished between the outcomes of patients with squamous versus nonsquamous cell histology. Multivariable Cox proportional hazards models and propensity score analyses facilitated adjustment for imbalance in measurable patient characteristics.

RESULTS

Of the 15,318 patients who received first‐line chemotherapy, 43.1% received carboplatin‐paclitaxel, 14.3% received carboplatin‐gemcitabine, 8.5% received carboplatin‐docetaxel, and 34.1% received other regimens. The median survival was 8.0 months (interquartile range [IQR], 3.5‐17.4 months) for carboplatin‐paclitaxel, 7.3 months (IQR, 3.4‐15.2 months) for carboplatin‐gemcitabine, and 7.5 months (IQR, 3.2‐16.0 months) for carboplatin‐docetaxel. Both multivariable and propensity score‐adjusted Cox models demonstrated a slight inferiority associated with carboplatin‐gemcitabine or carboplatin‐docetaxel versus carboplatin‐paclitaxel, with a hazard ratio of 1.10 (95% confidence interval, 1.04‐1.15) and 1.09 (95% confidence interval, 1.02‐1.16), respectively, in propensity score‐stratified models. Among the subgroup of 2063 patients with squamous carcinoma, propensity score‐stratified analyses had a higher risk of death (hazard ratio, 1.20; 95% confidence interval, 1.07‐1.35) associated with carboplatin‐gemcitabine versus carboplatin‐paclitaxel.

CONCLUSIONS

Carboplatin‐paclitaxel was associated with slightly better survival compared with carboplatin‐gemcitabine or carboplatin‐docetaxel within the Medicare population with advanced NSCLC, and this was most pronounced for patients who had squamous cell histology. Cancer 2013;119:2048–2060. © 2013 American Cancer Society.
A morpholino‐based screen to identify novel genes involved in craniofacial morphogenesis
Authors: Melvin Vida Senkus , Feng Weiguo , Hernandez‐Lagunas Laura , Artinger Kristin Bruk , Williams Trevor
Published: April 2013

Background: The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. Results: This set of ∼80 genes was used for a high‐throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53‐dependent and ‐independent mechanisms were involved in the craniofacial abnormalities. Conclusions: This Morpholino‐based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human. Developmental Dynamics 242:817–831, 2013. © 2013 Wiley Periodicals, Inc.
The transcription factor sry‐related HMG box‐4 (SOX4) is required for normal renal development in vivo
Authors: Huang Jez , Arsenault Michel , Kann Martin , Lopez‐Mendez Carlos , Saleh Monique , Wadowska Dorota , Taglienti Mary , Ho Jacqueline , Miao Yuan , Sims David , Spears Jonathan , Lopez Alfonso , Wright Glenda , Hartwig Sunny
Published: April 2013

Background: The DNA‐binding transcription factor Wilms' Tumor Suppressor‐1 (WT1) plays an essential role in nephron progenitor differentiation during renal development. We previously used Wt1 chromatin‐immunoprecipitation coupled to microarray (ChIP‐chip) to identify novel Wt1 target genes that may regulate nephrogenesis in vivo. We discovered that all three members of the SoxC subfamily, namely, Sox4, Sox11, and Sox12, are bound by Wt1 in mouse embryonic kidneys in vivo. SoxC genes play master roles in determining neuronal and mesenchymal progenitor cell fate in a multitude of developmental processes, but their function in the developing kidney is largely unknown. Results: Here we show that all three SoxC genes are expressed in the nephrogenic lineages during renal development. Conditional ablation of Sox4 in nephron progenitors and their cellular descendants (Sox4nephron‐ mice) results in a significant reduction in nephron endowment. By postnatal day (P)7, Sox4nephron‐ renal corpuscles exhibit reduced numbers of Wt1+ podocytes together with loss of expression of the slit diaphragm protein nephrin. Sox4nephron‐ mice develop early‐onset proteinacious glomerular injury within 2 weeks of birth progressing to end‐stage renal failure within 5–9 months. Conclusions: Collectively, our results demonstrate an essential requirement of Sox4 for normal renal development in vivo. Developmental Dynamics 242:790–799, 2013. © 2013 Wiley Periodicals, Inc.
Community composition of root‐associated fungi in a Quercus‐dominated temperate forest: “codominance” of mycorrhizal and root‐endophytic fungi
Authors: Toju Hirokazu , Yamamoto Satoshi , Sato Hirotoshi , Tanabe Akifumi S. , Gilbert Gregory S. , Kadowaki Kohmei
Published: April 2013

In terrestrial ecosystems, plant roots are colonized by various clades of mycorrhizal and endophytic fungi. Focused on the root systems of an oak‐dominated temperate forest in Japan, we used 454 pyrosequencing to explore how phylogenetically diverse fungi constitute an ecological community of multiple ecotypes. In total, 345 operational taxonomic units (OTUs) of fungi were found from 159 terminal‐root samples from 12 plant species occurring in the forest. Due to the dominance of an oak species (Quercus serrata), diverse ectomycorrhizal clades such as Russula, Lactarius, Cortinarius, Tomentella, Amanita, Boletus, and Cenococcum were observed. Unexpectedly, the root‐associated fungal community was dominated by root‐endophytic ascomycetes in Helotiales, Chaetothyriales, and Rhytismatales. Overall, 55.3% of root samples were colonized by both the commonly observed ascomycetes and ectomycorrhizal fungi; 75.0% of the root samples of the dominant Q. serrata were so cocolonized. Overall, this study revealed that root‐associated fungal communities of oak‐dominated temperate forests were dominated not only by ectomycorrhizal fungi but also by diverse root endophytes and that potential ecological interactions between the two ecotypes may be important to understand the complex assembly processes of belowground fungal communities.
Formation mechanism of steep convergent intracontinental margins: Insights from numerical modeling
Authors: Chen Lin , Gerya Taras V. , Zhang Zhong‐Jie , Aitken Alan , Li Zhong‐Hai , Liang Xiao‐Feng
Published: April 2013

The margins surrounding the Tibetan Plateau show some diversity in topographic gradient. The most striking example is the eastern Tibetan margin bordered by the Longmen Shan range, which is characterized by a remarkably steep topography transition between eastern Tibet and the Sichuan Basin. There is significant uncertainty over whether this margin was formed by crustal shortening or lower‐crustal flow. To investigate the formation mechanism of steep convergent intracontinental margins, we conducted petrological‐thermomechanical numerical simulations based on the lithospheric structure and thermal state of the eastern Tibetan margin. Our numerical experiments demonstrate that a very steep topographic gradient, such as the eastern Tibetan margin, is an inherent characteristic of convergence between a hot and weak lithosphere with thick crust and a cold and strong lithosphere with thin crust. Although lower‐crustal flow has potentially contributed to the crustal thickness difference between the two convergent blocks, it is not a prerequisite for the growth of steep convergent intracontinental margin. Rather, the topography at the margin can be explained by a near isostatic response to crustal thickening resulting from shortening.
S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo
Authors: Ismail Heba M.S. , Hurd Paul J. , Khalil Mahmoud I.M. , Kouzarides Tony , Bannister Andrew , Gout Ivan
Published: April 2013

The activity of S6 kinases (S6K) is highly induced in cancer cells highlighting an essential role in carcinogenesis. The S6K family has two members: S6K1 and S6K2 which bear common as well as distinct features. In an attempt to identify S6K2 unique sequence features compared to S6K1, we applied extensive bioinformatic analysis and motif search approaches. Interestingly, we identified 14 unique protein signatures which are present in proteins directly connected to chromatin and/or involved in transcription regulation. Using chromatin binding assay, we biochemically showed that S6K2 is bound to chromatin as well as nuclear matrix cellular fractions in HEK293 cells. The presence of S6K2 in chromatin fractions raised the possibility that it may be in close proximity to a number of chromatin substrates. For that, we then searched for S6K phosphorylation consensus sites RXRXXT/S in mammalian proteins using the SWISS‐PROT database. Interestingly, we identified some potential phosphorylation sites in histone H3 (Thr45). Using in vitro kinase assays and siRNA‐based knockdown strategy; we confirmed that S6K2 but not S6K1 or AKT is essential for histone H3‐Thr45 phosphorylation in HEK293 cells. Furthermore, we show that the nuclear localisation sequence in the S6K2 C‐terminus is essential for this modification. We have found that, H3‐Thr45 phosphorylation correlates to S6K activation in response to mitogens and TPA‐induced cell differentiation of leukaemic cell lines U937, HL60 and THP1. Overall, we demonstrate that S6K2 is a novel kinase that can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation. J. Cell. Biochem. 115: 1048–1062, 2014. © 2013 Wiley Periodicals, Inc.
The zebrafish as a model for nociception studies
Authors: Malafoglia Valentina , Bryant Bruce , Raffaeli William , Giordano Antonio , Bellipanni Gianfranco
Published: April 2013

Nociception is the sensory mechanism used to detect cues that can harm an organism. The understanding of the neural networks and molecular controls of the reception of pain remains an ongoing challenge for biologists. While we have made significant progress in identifying a number of molecules and pathways that are involved in transduction of noxious stimuli, from the skin through the sensory receptor cell and from this to the spinal cord on into the central nervous system, we still lack a clear understanding of the perceptual processes, the responses to pain and the regulation of pain perception. Mice and rat animal models have been extensively used for nociception studies. However, the study of pain and noiception in these organisms can be rather laborious, costly and time consuming. Conversely, the use of Drosophila and Caenorhabditis elegans may be affected by the large evolutionary distance between these animals and humans. We outline here the reasons why zebrafish presents a new and attractive model for studying pain reception and responses and the most interesting findings in the study of nociception that have been obtained using the zebrafish model. J. Cell. Physiol. 228: 1956–1966, 2013. © 2013 Wiley Periodicals, Inc.
Isotachophoresis with counterflow in an open capillary: Computer simulation and experimental validation
Authors: Liu Bingwen , Ivory Cornelius F.
Published: April 2013

The purpose of applying a countercurrent flow to isotachophoretic migration is to increase the effective separation channel length during ITP. However, severe dispersion induced by applying a counterflow can be detrimental to ITP. This paper uses numerical simulations in a 2D axisymmetric domain to investigate the dispersion caused by a parabolic counterflow in open‐capillary ITP. Counterflow in these simulations was generated by applying a back pressure to stop the isotachophoretic stack, i.e., forming stationary ITP zones. It is found that dispersion is strongly related to analyte molecular diffusivity: R‐phycoerythrin, due to its small diffusivity, showed ∼20‐fold increase in zone width in stationary counterflow ITP, compared to ITP in the absence of counterflow, while fluorescein only had ∼10% increase in zone width under similar operating conditions. Applying the Taylor–Aris dispersion formula in counterflow ITP simulations provided only a rough estimate of the dispersion, e.g., overestimation of analyte zone widths. Experiments on counterflow ITP were conducted in a silica capillary that was covalently and dynamically coated to exclude electroosmosis effect. The counterflow was generated by adjusting the relative height of the fluids in the two reservoirs at the capillary ends. Good qualitative agreement between simulations and experiments was found.
Determination of glutathione and cysteine in yeasts by hydrophilic interaction liquid chromatography followed by on‐line postcolumn derivatization
Authors: Karakosta Theano D. , Tzanavaras Paraskevas D. , Themelis Demetrius G.
Published: April 2013

In the present study, we report a new method for the determination of two primary thiols, cysteine (CYS) and glutathione (GSH), by hydrophilic interaction LC. The polar analytes are separated isocratically using a mobile phase consisting of 65% acetonitrile/35% ammonium acetate (15 mmol/L, pH 2.0) and are detected at 285 nm following on‐line postcolumn derivatization by the thiol‐selective reagent methyl propiolate. The main figures of merit included linearity in the range of 5–200 μmol/L and an LOD 0.6 μmol/L for both compounds. The absence of matrix effect allowed the determination of CYS and GSH in various yeast samples. GSH was present in most of the samples at levels ranging between 0.9 and 3.1 mg/g, whereas CYS was determined in only one sample at a significantly lower concentration. In terms of accuracy, the percent recoveries ranged between 91.2 and 105.6% for GSH, and 91.6 and 106.9% for CYS.
Evaluating a prediction model for infant hearing loss
Authors: Lieu Judith E. C. , Ratnaraj Felicia , Ead Banan
Published: April 2013

Objectives/Hypothesis

The objective of this study was to determine whether a prognostic model using risk factors for hearing loss could predict the chance that infants who failed a newborn hearing screen would subsequently be found to have hearing loss diagnosed by auditory brainstem response testing.

Study Design

Individual retrospective case‐control study.

Methods

We studied 229 infants with hearing loss compared with 458 infants with normal hearing. All infants had undergone natural sleep or sedated auditory brainstem response, predominantly for not passing a newborn hearing screen. Risk factors, birth history, and other information were extracted via medical record review. Multiple logistic regression analyses identified independent predictors of hearing loss.

Results

Four risk factors were independently predictive of hearing loss diagnosed by sleep or sedated auditory brainstem response: prematurity, 5‐minute APGAR score ≤ 6, intracranial complication, and craniofacial abnormality. A prognostic model developed from these risk factors was associated with a 15% rate of hearing loss in stage I, 52% rate of hearing loss in stage II, and 96% rate of hearing loss in stage III.

Conclusions

The presence of any one of four independently predictive risk factors in infants who did not pass newborn hearing screen was associated with a 50% rate of hearing loss; having three or more was associated with a 90% rate of hearing loss. Knowing that an infant is at high risk of hearing loss can motivate parents to follow up with diagnostic auditory brainstem response testing so that early identification can lead to early intervention.

Level of Evidence

2b. Laryngoscope, 123:2873–2879, 2013
Neue gastfreundliche Wirtmoleküle
Authors: Meier Herbert , Cao Derong
Published: April 2013

Calixarene und Co. bekommen Gesellschaft von den Pillararenen, makrozyklischen Oligomeren aus 1,4‐Phenylen‐methylen‐Bausteinen. In ihren starren Hohlräumen finden ganz unterschiedliche Verbindungen Platz.
Unternehmensübergreifende Steuerung von Prozessen
Authors: Gerber Tobias , Webel Christian
Published: April 2013

Zu Unternehmenssoftware gehören Systeme, die technische Prozesse innerhalb eines Unternehmens steuern, aber auch Anwendungen, welche die gesamte Wertschöpfungskette abbilden. Dafür sind Informations‐ und eingebettete Systeme zu integrieren — innerhalb eines Unternehmens und zwischen verschiedenen Unternehmen.
Chemiekompetenzen von Schülern messen
Authors: Walpuski Maik , Sumfleth Elke
Published: April 2013

Wenn aktuell die Leistung von Schülerinnen und Schülern im Fach Chemie untersucht wird, so sprechen Bildungsforscher, Bildungspolitiker und die Medien in der Regel nicht von Wissenstests, sondern von Kompetenztests. Dabei stellt sich die Frage, ob eine Kompetenz mehr oder weniger als Wissen ist, etwas gänzlich Neues oder nur ein neues Wort für etwas, was man schon immer kannte.
The power method for tensor eigenproblems and limiting directions of Newton iterates
Authors: Dupont Todd F. , Ridgway Scott L.
Published: April 2013

We study the angular orientations of convergent iterates generated by Newton's method in multiple space dimensions. We show that the Newton iteration can be interpreted as a fixed‐point algorithm for solving a tensor eigenproblem. We give an extensive computational analysis of this tensor eigenproblem in two dimensions. In a large fraction of cases, the tensor eigenproblem has a discrete number of solutions to which the Newton directions converge quickly, but there is also a large fraction of cases in which the behavior is more complicated. We contrast the angular orientations of iterates generated by Newton's method with the corresponding directions of the continuous Newton algorithm. Copyright © 2013 John Wiley & Sons, Ltd.
Polydienes possessing terminal ionic groups. Part 2. Preparation of polydienes with terminal borate groups
Authors: Morrell Richard K. , Service David M. , Stewart Malcolm J. , Viguier Michel , Richards David H.
Published: April 2013

Methods are described by which various organolithium species are reacted with triphenylborane to generate materials possessing borate functionality. Comparison is made between experiments involving simple alkyllithium compounds, and those involving living anionic polybutadienes. Evidence is presented to show that using living polybutadienes at temperatures below 0°C, the reaction proceeds with very high efficiency, and that overall conversion to borate‐functionalised polymer is virtually quantitative.
Synthesis and characterisation of mercury‐terminated polymers: Applications to diblock copolymer formation via anionic‐radical transformations
Authors: Lindsell W. Edward , Service David M. , Soutar Ian , Richards Late David H.
Published: April 2013

Reactions in tetrahydrofuran (THF) of anionically produced polystyryllithium (PsLi) with excess mercury(II) compounds, HgX2 (X = Cl, Br, OAc), or PhHgCl form mercury‐terminated polymers, PsHgX (X = Cl, Br, OAc or Ph, respectively), which have been characterised by g.p.c. and by elemental analyses using neutron activation. Similar reactions of PsLi with half‐molar quantities of HgX2 yield no mercury‐containing products, such as Hg(Ps)2, and produce only coupled homopolystyrene, Ps‐Ps, accompanied by PsX and PsH. Also, PsLi and HgI2, in various reactant ratios, produce only Ps2 and PsI. Reactions of PsHgX (X = Cl or Br) with PsLi, n BuLi and HgX2 are reported.

Thermolysis of PsHgX (X = Cl or Br) in the presence of methyl methacrylate (MMA) at temperatures ≥90°C afford block copolymers Ps‐PMMA via homolytic cleavage of Ps‐Hg bonds and radical propagation. Homolytic cleavage of Ps‐Hg by oxidation with CuBr2 or by reaction with HgBr2 in the presence of MMA also forms diblock copolymer. G.p.c. and other studies on the diblock copolymers are reported.
Microstructure and mechanism of formation of the ring‐opened polymers of anti‐7‐ethylbicycio[2.2.1]hept‐2‐ene initiated with metathesis catalysts
Authors: Greene Ruth M. E. , Ivin Kenneth J. , Milligan Brian D. , Rooney John J.
Published: April 2013

A 52:48 mixture of syn‐ and anti‐7‐ethylbicyclo[2.2.1]hept‐2‐ene was submitted to polymerization by five metathesis catalysts: RuCl3. 3H20, IrCl3.3H2O, (mes)W(CO)3/EtAlCl2/norbornene epoxide, WCl6/Me4Sn, and ReCl5. Only the anti isomer undergoes ring‐opening polymerization, from which it is concluded that propagation occurs by attack on the exo face. The fraction of cis double bonds and tacticities were determined from 13C n.m.r. spectra of the polymers and their hydrogenated products. For the unsaturated polymers these were respectively: 0 00 atactic, 0 21 atactic, 0 43 tactic (c/r, t/m), 059 atactic, 1 00 syndiotactic. The atactic polymers all show a bias towards m dyads for both cis and trans double bonds. This indicates an influence of the configuration of the polymer chain attached to the propagating metal‐carbene complex on the stereochemistry of addition of monomer.
Preparation of copolymers through cationic grafting. 6. Investigation of the mechanisms of transfer reactions in the polymerisation of α‐methylstyrene
Authors: Taxi Mohammed , Tardi Michel , Polton Alain , Sigwalt Pierre
Published: April 2013

The mechanisms of transfer reactions in the polymerisation of α‐methylstyrene initiated with AlEt2Cl from — 70°C to — 30°C have been investigated using cationic grafting on a poly(isobutylene‐co‐chloromethylstyrene). Besides the bimolecular transfer to the monomer, evidence has been found for the occurrence of a kinetically unimolecular transfer reaction, which may be attributed to transfer to the counter ion but might also result from transfer to the solvent. Transfer is not important at — 70°C and — 50°C. From the variation with conversion of the molar concentration of homopolymer chains (formed by transfer), transfer constants could be estimated (for transfer to monomer ktrM/kp = 10‐5 at −70°C and 10‐4 at −50°C; for unimolecular transfer ktrkp = 5 × 10‐5 mol litre−1 at −70°C and 4 × 10‐4mol litre−1 at −50°C). At both temperatures, initiation is not instantaneous but takes place throughout the polymerisation. At — 30°C, initiation seems to be rapid and quantitative, all the chloromethyl groups are modified and transfer becomes preponderant.
Differential scanning calorimetric investigation of curing of resins formed from furfural and various phenols
Authors: Arora Pravin B. , Patel Vithal S. , Patel Shanti R.
Published: April 2013

Curing reactions of adequately characterized phenol‐furfural, o‐chlorophenol‐furfural, P‐chlorophenol‐furfural and p‐tert‐butyl phenol‐furfural resins with hexamine were studied by differential scanning calorimetry. The data are analyzed by appropriate empirical relations with a view to examining their applicability to the present sets of data and to estimating kinetic parameters of the curing reactions.
Non‐ionic polystyrene latices in aqueous media
Authors: Ottewill Ronald H. , Satgurunathan Rajasingham , Waite Frederick A. , Westby Margaret J.
Published: April 2013

Colloidally stable non‐ionic polystyrene latices were prepared in aqueous media, with a narrow distribution of particle sizes, using a nonyl phenol polyethylene glycol condensate as the surface‐active agent, methoxy polyethylene glycol methacrylate as the comonomer‐stabiliser and ascorbic acid‐hydrogen peroxide as the initiator system. For comparison, a typical charge‐stabilised polystyrene latex was also prepared using an anionic surface‐active agent and potassium persulphate as the initiator. These latices were characterised using transmission electron microscopy, conductometric titration and microelectrophoresis. The stability of the latices to the addition of electrolyte was examined and also the stability to freeze‐thaw conditions. The glass transition temperatures of the latices were also determined.
Interfacial reactions in carbon—epoxy composites
Authors: Garton Andrew , Stevenson William T. K. , Wang Shiping
Published: April 2013

A series of models for the carbon‐epoxy interphase are developed comprising high surface area carbon blacks, crushed carbon fibres and chopped carbon fibres dispersed in epoxy matrices. The carbon surfaces are modified by oxidative or reducing treatments and the effects of the modified carbon surfaces on the epoxy cross‐linking processes are examined by differential scanning calorimetry and infrared spectroscopy. Oxidised carbon surfaces retard the cure of anhydride‐epoxy systems by adsorption of the tertiary amine catalyst. Oxidised carbon surfaces initially accelerate epoxy‐amine reactions but inhibit the later stages of the reaction such that the final level of cure is reduced. These modifications to the chemistry of the interfacial region influence the properties of carbon‐epoxy composites.
Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target
Authors: Pendini Nicole R. , Yap Min Y. , Polyak Steven W. , Cowieson Nathan P. , Abell Andrew , Booker Grant W. , Wallace John C. , Wilce Jacqueline A. , Wilce Matthew C. J.
Published: April 2013

The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug‐resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo‐ and apo‐forms of SaBPL using X‐ray crystallography. We also present small‐angle X‐ray scattering data of SaBPL in complex with its biotin‐carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl‐5′‐AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery.
Ab initio study of the effects of pressure and strain on electron–phonon coupling in IV and III–V semiconductors
Authors: Sjakste Jelena , Vast Nathalie , Jani Hariom , Obukhov Sergey , Tyuterev Valeriy
Published: April 2013

In this work, we examine the pressure and biaxial tensile strain dependence of the intervalley electron–phonon matrix elements in the lowest conduction band of GaAs, GaP, Si and Ge within the density functional perturbation theory. We study both individual transitions and average deformation potential values which can be used as parameters in transport simulations. In the case of a hydrostatic pressure, we draw the general conclusion that the hydrostatic pressure dependence of the intervalley electron–phonon matrix elements can be safely neglected in the interpretation of most commonly studied phenomena. In contrast, the case of a biaxial strain in silicon shows that strain‐dependence should be taken into account in calculations of the intervalley electron–phonon matrix elements.
Investigations of carrier scattering into L‐valley in λ = 3.5 µm InGaAs/AlAs(Sb) quantum cascade lasers using high hydrostatic pressure
Authors: Aldukhayel A. , Jin S. R. , Marko I. P. , Zhang S. Y. , Revin D. G. , Cockburn J. W. , Sweeney S. J.
Published: April 2013

In order to identify the performance limitations of InGaAs/AlAs(Sb) quantum cascade lasers, experimental investigations of the temperature and pressure dependencies of the threshold current (Ith) were undertaken. Using the theoretical optical phonon current (Iph) and carrier leakage (Ileak) to fit the measured threshold current at various pressures, we show that the electron scattering from the top lasing level to the upper L‐minima gives rise to the increase in Ith with pressure and temperature. It was found that this carrier leakage path accounts for approximately 3% of Ith at RT and is negligible at 100 K.
Free energy loss analysis of heterojunction solar cells
Authors: Brinkmann Nils , Micard Gabriel , Schiele Yvonne , Hahn Giso , Terheiden Barbara
Published: April 2013

For the first time we present a free energy loss analysis (FELA) of heterojunction silicon solar cells (HSSC) to study the influence of the intrinsic buffer layer thickness (tbuffer) on the solar cell efficiency (η). The main advantage of the FELA is that the impact of various loss mechanisms can be directly expressed in absolute percentage of η. Furthermore, it is possible to extract the magnitude of every loss for each region of the solar cell. All quantities required to perform the FELA are obtained by the simulation software AFORS‐HET. The FELA yields an optimum efficiency of 21.24% for tbuffer ≈ 5 nm. The efficiency drop for tbuffer £ 5 nm is ascribed to a lower maximum usable generated power ΦG(22.84% @ 2 nm, 23.98% @ 5 nm). Lower efficiencies for tbuffer ³ 5 nm are attributed to the increased transport loss of holes in the intrinsic buffer layer (0.05% @ 2 nm, 0.65% 8 nm). The η values yielded by the FELA are in agreement with the ones calculated by AFORS‐HET, demonstrating the applicability of the FELA to the HSSC concept. Therewith, we demonstrate that the FELA can be employed to obtain a deeper understanding of the HSSC concept. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pérez Art Museum Miami: Hurrikan‐resistente Verglasungen
Authors: Teich Martien , Oppe Matthias , Jungjohann Hauke , Helbig Thorsten , Schmid Heiko
Published: April 2013

In Miami, Florida entsteht zur Zeit das Pérez Art Museum Miami nach Plänen von Herzog & de Meuron. Miami liegt in einer durch Hurrikans gefährdeten Zone mit hohen Windlasten. Entsprechend groß sind die Anforderungen an die von seele und Knippers Helbig entwickelte gläserne Außenhülle des Gebäudes. Eine Besonderheit sind die vertikalen Fassadenpfosten aus ultrahochfestem Faserbeton (UHPC). Die Verglasung wird mittels in den Beton eingegossener Edelstahlschienen an den Pfosten angebunden. Aufgrund der Hurrikangefährdung sind die Scheiben mit jeweils zwei laminierten Doppelverglasungen ausgeführt. Bislang wurden Scheiben dieser Größe (max. 5200 × 2300 mm) in einer Zone mit derart hohen Windlasten noch nicht ausgeführt. In einem mehrstufigen Hurrikantest stellen alle Elemente der Fassade ihre Widerstandsfähigkeit unter Beweis.

Pérez Art Museum Miami: hurricane resistant glazing. The Pérez Art Museum Miami currently under construction in Miami, Florida is designed by Herzog & de Meuron. The vertical glass facades have been designed in close collaboration between seele and Knippers Helbig, fabricated and installed by seele. Miami is well known to be located in a region with high wind loads and risk of hurricanes, requiring compliance to demanding hurricane resistant specifications for the glass façades. Up until now, the large glass units that are planned ‐ up to approx. 5.20 m high and 2.30 m wide ‐ have not been used in this hurricane prone region. All the elements of the façade must prove their robustness in hurricane tests. The panes of glass are fixed to stainless steel rails cast into the ultra‐high performance concrete (UHPC) mullions. The joint is either concealed by narrow pressure plates or a toggle‐system is used to fix the glass panels to the mullions. Owing to the threat of hurricanes, each pane consists of two double‐glazing units with a reinforcing interlayer in between. Here, a demanding owner and even more demanding architects, with the help of seele and Knippers Helbig, are pushing material limits.
Begehbare und befahrbare Verglasungen
Authors: Siebert Barbara , Pistora Arthur
Published: April 2013

Planmäßig begehbare Verglasungen sind in der aktuellen Architektur sehr verbreitet. In einigen Fällen sollen diese Verglasungen auch für das Befahren mit Fahrzeugen ausgelegt werden. In Deutschland können begehbare Verglasungen entsprechend der TRLV und zweier allgemeiner bauaufsichtlicher Zulassungen ausgeführt werden. Mit der Veröffentlichung des Entwurfes der DIN 18008‐5:2011‐10 gibt es nun auch eine neue Bemessungsgrundlage beruhend auf Teilsicherheitsbeiwerten. In dieser noch nicht baurechtlich eingeführten Norm werden Glasaufbauten mit bereits nachgewiesener Stoßsicherheit und Resttragsicherheit angegeben. In dieser Veröffentlichung wird gezeigt, wie begehbare und befahrbare Verglasungen nach den noch geltenden TRLV und nach der zukünftigen Normenreihe DIN 18008 bemessen werden können.

Glazing accessible for persons and vehicles. In the today architecture glazing accessible for persons are very popular. In some cases the glazing must be accessible for cars and even trucks. In Germany, glazings accessible for persons can be build according to the TRLV or according to two general building approvals. Other accessible glazings need a special building permit from the building authorities. This paper shows the static calculation for accessible glazing according to the current building regulation TRLV and for the new regulation DIN 18008‐5.