bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of cyclins in high‐density cultured cells and in vivo tumor cells
Authors: Min Jiang , Wang Xiangyang , Tong Yixin , Li Xiaolan , Tao Deding , Hu Junbo , Xie Daxing , Gong Jianping
Published: August 2012

It is widely assumed that during the mammalian cell cycle, four major cyclins, including G1 cyclins (D, E) and mitotic cyclins (A, B1), are expressed in an orderly scheduled pattern in exponentially cultured cells. In high‐density cultured cells and in vivo growing cells, whether these cyclins are expressed in the same pattern remains unknown. In this study, we investigated the expression of cyclins by flow cytometry and western‐blotting in cultured MOLT‐4 and HepG2 cells at high‐density. We found that, in high‐density cultures, the expression levels of cyclin D, E, and A within each cell cycle phase was less than their levels in low‐density cultures. Cyclin B1 was slightly reduced in G2/M phase and unexpectedly expressed in G1 phase. The cyclin B1 expressed in G1 phase was localized mainly in the cytoplasm, and its level was positively correlated with apoptosis. Moreover, we obtained similar cyclins expression pattern in inoculated HepG2 tumor cells from immune‐deprived mice and leukemic cells from leukemia patients. These findings describe an altered pattern of cyclin expression in high‐density cultured cells as well as in vivo tumor cells. We suggest that high‐density cultures might mimic the in vivo growth conditions and such experimental situation may be useful for cell cycle research.
Interactive effects between diet and genotypes of host and pathogen define the severity of infection
Authors: Zhang Ji , Friman Ville‐Petri , Laakso Jouni , Mappes Johanna
Published: August 2012

Host resistance and parasite virulence are influenced by multiple interacting factors in complex natural communities. Yet, these interactive effects are seldom studied concurrently, resulting in poor understanding of host‐pathogen‐environment dynamics. Here, we investigated how the level of opportunist pathogen virulence, strength of host immunity and the host condition manipulated via diet affect the survival of wood tiger moth Parasemia plantaginis (Arctidae). Larvae from “low cuticular melanin” and “high cuticular melanin” (considered as low and high pathogen resistance, respectively) selection lines were infected with moderately and highly virulent bacteria strains of Serratia marcescens, while simultaneously manipulating host diet (with or without antibacterial compounds). We measured host survival and food preference before and after infection to test whether the larvae “self‐medicate” by choosing an anti‐infection diet (Plantago major, i.e., plantain leaf) over lettuce (Lactuca sativa). “High melanin” larvae were more resistant than “low melanin” larvae to the less virulent strain that had slower growth and colonization rate compared with the more virulent strain. Cuticular melanin did not enhance survival when the larvae were infected with the highly virulent strain. Anti‐infection diet enhanced survival of the “high melanin” but not the “low melanin” hosts. Survival was dependent on family origin even within the melanin selection lines. Despite the intrinsic preference for lettuce, no evidence of self‐medication was found. These results demonstrate that the relative benefit of host cuticular melanin depends on both diet and pathogen virulence: plantain diet only boosted the immunity of already resistant “high melanin” hosts, and cuticular melanin increased host survival only when infected with moderately virulent pathogen. Moreover, there was considerable variation in host survival between families within both melanin lines suggesting genetic basis for resistance. These results indicate that although melanin is an important predictor of insect immunity, its effect on disease outcomes greatly depends on other interacting factors.
Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts
Authors: Šafář Peter , Žúžiová Jozefína , Marchalín Štefan , Prónayová Nadežda , Švorc Ľubomír , Vrábel Viktor , Šesták Sergej , Rendić Dubravko , Tognetti Vincent , Joubert Laurent , Daïch Adam
Published: August 2012

Six novel enantiopure epimeric indolizidinediols have been easily prepared in high yields by an effective and well‐established regioselective THF ring‐opening reaction as a key step. Quarternization of these species was also studied and comparison was made to the quaternizations of other substituted indolizidines. Importantly, a combined theoretical DFT‐QTAIM study has cast light on the various factors that explain the observed conformational selectivity. The inhibitory properties of the six synthesized indolizidines were then investigated against the recombinant Golgi α‐mannosidase‐IIb (dGMIIb) and lysosomal α‐mannosidase (dLM408), human homologues of Drosophila melanogaster. Among the tested compounds, two of them, 4a and 4b, exhibited a pH‐dependent inhibition of dGMIIb at the milimolar level (IC50 = 3.5 or 1.7 mM at pH 5.8 or 6.5, respectively) without affecting the activity of dLM408.
Chiral NHC Ligands for the Copper‐Catalyzed Asymmetric Conjugate Addition of Grignard Reagents
Authors: Germain Nicolas , Magrez Magaly , Kehrli Stefan , Mauduit Marc , Alexakis Alexandre
Published: August 2012

In this paper, we disclose our recent advances in the copper‐catalyzed enantioselective conjugate addition of Grignard reagents to 3‐substituted cyclic enones. Several new N‐heterocyclic carbene (NHC) ligands have been synthesized in high yields by starting from inexpensive materials. These new NHCs were evaluated as ligands for copper, for the Michaeladdition of ethylmagnesium bromide leading to chiral 3,3‐disubstituted cyclohexanones (up to 93 % ee). The best ligand was then engaged in conjugate additions of various Grignard reagents, allowing the formation of quaternary centers with high levels of regio‐ and enantioselectivity with only 0.75 mol‐% catalyst loading. The reaction is also robust to scale‐up. The addition of ethylmagnesium bromide for the construction of a 3,3‐disubstituted cyclopentanone (up to 86 % ee), a synthetically useful chiral synthon, is noteworthy. A tentative mechanism for the catalytic cycle is also discussed.
Controlled Switching of Multicomponent Heterocyclizations of 5‐Amino‐N‐arylpyrazole‐4‐carboxamides, 1,3‐Cyclohexanediones, and Aldehydes
Authors: Chebanov Valentin A. , Saraev Vyacheslav E. , Shishkina Svetlana V. , Shishkin Oleg V. , Musatov Vladimir I. , Desenko Sergey M.
Published: August 2012

Multicomponent heterocyclization of 5‐amino‐N‐arylpyrazole‐4‐carboxamides, 1,3‐cyclohexanediones, and aromatic aldehydes was studied, and reaction conditions allowing selective switching between two directions were found. When the reaction was carried out under thermal heating or ultrasonication at room temperature, formation of linear pyrazoloquinoline‐3‐carboxamides was observed. Isomeric angular heterocycles were obtained by ultrasonic‐assisted synthesis at ambient temperature in the presence of HCl catalyst. Treatment with 2 equiv. of 1,3‐diketone in boiling N,N‐dimethylformamide/HCl gave a mixture of pyrazoloquinoline‐3‐carboxamides and unusual acridin‐10‐yl‐pyrazole‐4‐carboxamides, which showed hindered rotation of the pyrazole fragment around the C–N bond.
Characteristics‐based boundary conditions for the Euler adjoint problem
Authors: Hayashi Marcelo , Ceze Marco , Volpe Ernani
Published: August 2012

Over the last decade, the adjoint method has been consolidated as one of the most versatile and successful tools for aerodynamic design. It has become a research area on its own, spawning a large variety of applications and a prolific literature. Yet, some relevant aspects of the method remain relatively less explored in the literature. Such is the case with the adjoint boundary problem. In particular for Euler flows, both fluid dynamic and adjoint equations entail complementary Riemann problems, and these yield boundary conditions that are fully consistent with well‐posedness. In the literature, this approach has been pursued solely in terms of Riemann variables. This work formulates the adjoint boundary problem so as to correspond precisely to that imposed on the flow, as it is given in terms of primitive variables. Test results have shown to be in agreement with the traditional approach for external flow problems. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis of Bis(imidazole‐2‐thion‐4‐yl)phosphanes
Authors: Sauerbrey Susanne , Majhi Paresh Kumar , Schwieger Sebastian , Arduengo Anthony J. , Streubel Rainer
Published: August 2012

Novel bis(imidazole‐2‐thion‐4‐yl)‐ phosphanes (2a–d) were synthesized via lithiation of the precursor imidazole‐2‐thiones followed by the phosphanylation reaction. Oxidation of bis(imidazole‐2‐thion‐4‐yl)phosphane 2b–d with elemental sulfur and selenium led selectively and in good yields to the P‐thio (3b–d) and P‐seleno (4c) derivatives of bis(imidazole‐2‐thion‐4‐yl)phosphanes, respectively. The treatment of 2a,c with phosphorus trichloride gives the corresponding P‐chloro derivatives 5a,c. These compounds were unambiguously characterized by elemental analyses, spectroscopic and spectrometric methods, in addition by single‐crystal X‐ray structure analysis in the case of 2d. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–7, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21043
Determination of Picogram Amounts of Dihydroxybenzenes in Water Samples with Luminol–lysozyme Chemiluminescence System
Authors: Haixiang Zhao , Xijuan Tan , Zhenghua Song
Published: August 2012

An ultrasensitive method for the determination of dihydroxybenzens by flow injection (FI) chemiluminescence (CL) analysis was proposed for the first time. It was found that the CL intensity of luminol–lysozyme system could be significantly inhibited by dihydroxybenzens. The CL intensity decrements were linear with the logarithm of dihydroxybenzens concentrations over the ranges of 1.0 ∼ 700 pg mL‐1 for hydroquinone (HQ), 5.0 ∼ 700 pg mL‐1 for catechol (CT) and 10 ∼ 7000 pg mL‐1 for resorcinol (RS), with the corresponding limits of detection of 0.7, 3.0 and 7.0 pg mL‐1, respectively. The proposed method was successfully applied to the determination of CT in tap water, rain water, river water and HQ in waste photographic developer samples, with recoveries from 93.5 to 105.8% and relative standard deviations (RSDs) less than 4.0% (n = 5). The possible interaction mechanism of lysozyme with dihydroxybenzens was discussed, and CT to lysozyme's binding constant and the thermodynamic parameters were given by the homemade FI–CL model. The results shown that the binding of dihydroxybenzens to lysozyme was spontaneous with the hydrophobic force.
Nanocomposite Silica Aerogel Activated Carbon: Preparation, Characterization and Application to Remove Lead(II) from Aqueous Solutions
Authors: Fariba Tadayon , Mina Hosseini , Shiva Motahar
Published: August 2012

Anovel nanocomposite adsorbent, Silica aerogel activated carbon (SA‐AC) has been prepared for the purpose of removing lead ions from aqueous solution in batch process. The nanocomposite was characterized by Fourier transform infrared spectra (FTIR) and scanning electron microscope (SEM). In the present investigation, Pb(II) adsorption experiments on nanocomposite were conducted on aqueous solution at different initial Pb(II) concentration, pH of the solution, adsorption temperature, adsorbent dosage and contact time. Optimum pH for the adsorption was found to be 6 with corresponding adsorbent dosage level of 0.5 g and 60 °C temperature. The equilibriumwas achieved within 30 min of contact time. It is remarkable that using the developed nanocomposite absorbent, more than 90% of Pb(II) can be removed under desirable experimental conditions. The efficiency of the ions adsorption was determined using atomic absorption spectroscopy. Langmuir and Freundlich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data was given by the Freundlich isotherm equation. Desorption experiments by elution of the adsorbent with nitric acid show that the nanocomposite could be reused without significant losses of its initial properties.
An Efficient, Mild and Scalable Synthesis of Bioactive Compounds Containing the Angelicin Scaffold
Authors: Hui‐Yi Shiao , Ching‐Chuan Kuo , Jim‐Tong Horng , Shin‐Ru Shih , Sui‐Yuan Chang , Chun‐Chen Liao , John T.‐A. Hsu , Prashanth Kumar Amancha , Yu‐Sheng Chao , Hsing‐Pang Hsieh
Published: August 2012

An efficient, mild and scalable synthesis of angelicin scaffold based compounds was developed. Particularly, the new synthetic route described here circumvents the need for the previously reported key Fries rearrangement step, which uses impractically harsh conditions. The new methodology is applied to the synthesis of several, previously reported analogs of angelicin which have potent anti‐influenza and anti‐cancer activities.
Changes in daily extreme temperatures in the extra‐Carpathians regions of Romania
Authors: Croitoru Adina‐Eliza , Piticar Adrian
Published: August 2012

Changes in daily extreme temperatures have been identified in many studies conducted at local, regional or global scales. For Romanian territory, only little research on this issue was done. In this article, the extra‐Carpathians regions of Romania located southward and eastward from the Carpathians Chain were considered. This study is focused on analyzing daily extreme temperature trends at a regional scale (eastern, southern and southeastern regions of Romania) across 50 years (1961–2010). Data sets of daily minimum and maximum temperature recorded in 14 weather stations were analyzed. The main goal was to find changes in extreme daily temperatures using a set of 20 indices adopted from the core indices developed by ETCCDMI with appropriate modifications to suit to the analyzed territory. The main results suggest that regional temperature trends at the scale of extra‐Carpathians areas of Romania are similar to those calculated for global and European continental scales; the climate has become warmer during the last decades. It has been identified that both extreme daily maximum and minimum temperatures have increased in the analyzed areas. For all the indices related to hot temperature most trends are significantly positive. The strongest increase was detected for hot related extremes such as summer days and tropical nights as well as for maximum values of maximum and minimum daily temperatures. For indices related to cold there are different sign slopes, but negative slopes prevail, especially for number of days under a defined threshold. This is also an evidence of the important warming in the area. Generally, it was found that the daily maximum temperature is getting more extreme, whereas the minimum is getting less extreme. Copyright © 2012 Royal Meteorological Society
A daytime over land algorithm for computing AVHRR convective cloud climatologies for the Iberian Peninsula and the Balearic Islands
Authors: Azorin‐Molina Cesar , Baena‐Calatrava Rafael , Echave‐Calvo Imanol , Connell Bernadette H. , Vicente‐Serrano Sergio M. , López‐Moreno Juan I.
Published: August 2012

A daytime over land multispectral cloud detection algorithm is presented to derive accurate convective cloud climatologies with high spatial resolution (1.1 km) over the Iberian Peninsula (IP) and the Balearic Islands (BI). The cloud detection scheme was designed to process Advanced Very High Resolution Radiometer (AVHRR) HRPT data and is tested here on NOAA‐17 morning (0900–1200 UTC) and NOAA‐16 afternoon (1200–1500 UTC) overpasses for the warm 6‐month study period May–October. The algorithm consists of four spectral threshold tests applied to each pixel. Test 1 corresponds to the snow‐ice removal, test 2 is the thermal infrared test, test 3 is the albedo or visible test and test 4 is the ratio between near‐infrared and visible channels. The algorithm discretizes all AVHRR data into four groups called cloud‐filled, cloud‐free, snow‐ice and snow‐free radiances. The high‐resolution convective cloud masks are obtained by subtracting snow‐ice pixels from cloudy ones. In this article, a detailed description of the convective cloud detection scheme and the sources of error detected for each test are given, and the first seasonal and monthly regional convective cloud frequency composites are presented. Future applications of the newly proposed threshold algorithm in climate and meteorology are also discussed in this article, particularly the production of convective cloud composites for climate monitoring of storms over the IP and BI.
Quantification of ampicillin in bovine milk by coupled‐column ultrahigh‐performance liquid chromatography‐tandem mass spectrometry
Authors: Moura Franciane , de Almeida Fernando G. , Rebelo Lopes Bianca , Bezerra Cass Quezia
Published: August 2012

This work reports the use of two‐dimensional (2D) liquid chromatography system coupled with a tandem mass spectrometry for the quantification of ampicillin in bovine milk. A restrict access media column (RAM‐BSA C8, 50 × 2.1 mm, Luna, 10 μm, 100 Å) was used in the first dimension in order to exclude macromolecules, while an ACQUITY UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column was used in the second dimension. Three different channels of selected reaction monitoring (SRM) were used: 350 > 106 m/z, 350 > 160 m/z, and 350 > 192 m/z. The first transition was used for the quantification (higher intensity), and latter two for confirmation. The developed method is simple and requires a total analysis time of only 14 min/sample. The sample treatment involved only a centrifugation step for 20 min. The validated method has been successfully applied to monitor AMP residues in raw milk samples. To our knowledge, this is the first study to report the use of ultrahigh‐performance liquid chromatography (UHPLC) in 2D configuration.
HPLC separation of dihydropyridine derivatives enantiomers with emphasis on elution order using polysaccharide‐based chiral columns
Authors: Jibuti George , Mskhiladze Antonina , Takaishvili Nino , Karchkhadze Marina , Chankvetadze Lali , Farkas Tivadar , Chankvetadze Bezhan
Published: August 2012

The separation of enantiomers of five chiral dihydropyridine derivatives was studied on five different polysaccharide‐based chiral HPLC columns with various normal‐phase (NP), polar organic, and reversed‐phase eluents. Along with the successful separation of analyte enantiomers, the emphasis of this study was on enantiomer elution order (EEO) with various columns and mobile phase composition. The interesting phenomenon of reversal of EEO, recently reported in the case of amlodipine (AML) depending on the concentration of formic acid in acetonitrile, was also confirmed with NP eluents. Under RP conditions at relatively low water content, the EEO of AML could also be reverted by varying the concentration of formic acid in the mobile phase. However, at higher water content the same parameter did not affect the EEO, but only induced gradual decrease in resolution up to complete co‐elution of enantiomers. Additionally, in organic‐aqueous mobile phases retention factors decreased with increasing water content but only up to 20% (v/v), while above this concentration the expected typical RP behavior was observed. The presence of the commonly used additive diethylamine in the mobile phase seems important for observing a reversal in EEO with increasing concentration of formic acid. The reversal of the EEO was characteristic of AML only and was not observed for any of other dihydropyridines included in this study.
An activator for pyruvoyl‐dependent l‐aspartate α‐decarboxylase is conserved in a small group of the γ‐proteobacteria including Escherichia coli
Authors: Nozaki Shingo , Webb Michael E. , Niki Hironori
Published: August 2012

In bacteria, β‐alanine is formed via the action of l‐aspartate α‐decarboxylase (PanD) which is one of the small class of pyruvoyl‐dependent enzymes. The pyruvoyl cofactor in these enzymes is formed via the intramolecular rearrangement of a serine residue in the peptide backbone leading to chain cleavage and formation of the covalently‐bound cofactor from the serine residue. This reaction was previously thought to be uncatalysed. Here we show that in Escherichia coli, PanD is activated by the putative acetyltransferase YhhK, subsequently termed PanZ. Activation of PanD both in vivo and in vitro is PanZ‐dependent. PanZ binds to PanD, and we demonstrate that a PanZ(N45A) site‐directed mutant is unable to enhance cleavage of the proenzyme PanD despite retaining affinity for PanD. This suggests that the putative acetyltransferases domain of PanZ may be responsible for activation to enhance the processing of PanD. Although panD is conserved among most bacteria, the panZ gene is conserved only in E. coli‐related enterobacterial species including Shigella, Salmonella, Klebsiella and Yersinia. These bacteria are found predominantly in the gut flora where pantothenate is abundant and regulation of PanD by PanZ allows these organisms to closely regulate production of β‐alanine and hence pantothenate in response to metabolic demand.
Molecular dynamics simulation of the last step of a catalytic cycle: Product release from the active site of the enzyme chorismate mutase from Mycobacterium tuberculosis
Authors: Choutko Alexandra , van Gunsteren Wilfred F.
Published: August 2012

The protein chorismate mutase MtCM from Mycobacterium tuberculosis catalyzes one of the few pericyclic reactions known in biology: the transformation of chorismate to prephenate. Chorismate mutases have been widely studied experimentally and computationally to elucidate the transition state of the enzyme catalyzed reaction and the origin of the high catalytic rate. However, studies about substrate entry and product exit to and from the highly occluded active site of the enzyme have to our knowledge not been performed on this enzyme. Crystallographic data suggest a possible substrate entry gate, that involves a slight opening of the enzyme for the substrate to access the active site. Using multiple molecular dynamics simulations, we investigate the natural dynamic process of the product exiting from the binding pocket of MtCM. We identify a dominant exit pathway, which is in agreement with the gate proposed from the available crystallographic data. Helices H2 and H4 move apart from each other which enables the product to exit from the active site. Interestingly, in almost all exit trajectories, two residues arginine 72 and arginine 134, which participate in the burying of the active site, are accompanying the product on its exit journey from the catalytic site.
Bacterial collagen‐binding domain targets undertwisted regions of collagen
Authors: Philominathan Sagaya Theresa Leena , Koide Takaki , Matsushita Osamu , Sakon Joshua
Published: August 2012

Clostridium histolyticum collagenase causes extensive degradation of collagen in connective tissue that results in gas gangrene. The C‐terminal collagen‐binding domain (CBD) of these enzymes is the minimal segment required to bind to a collagen fibril. CBD binds unidirectionally to the undertwisted C‐terminus of triple helical collagen. Here, we examine whether CBD could also target undertwisted regions even in the middle of the triple helix. Collageneous peptides with an additional undertwisted region were synthesized by introducing a Gly → Ala substitution [(POG)xPOA(POG)y]3, where x + y = 9 and x > 3). 1H–15N heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) titration studies with 15N‐labeled CBD demonstrated that the minicollagen binds to a 10 Å wide 25 Å long cleft. Six collagenous peptides each labeled with a nitroxide radical were then titrated with 15N‐labeled CBD. CBD binds to either the Gly → Ala substitution site or to the C‐terminus of each minicollagen. Small‐angle X‐ray scattering measurements revealed that CBD prefers to bind the Gly → Ala site to the C‐terminus. The HSQC NMR spectra of 15N‐labeled minicollagen and minicollagen with undertwisted regions were unaffected by the titration of unlabeled CBD. The results imply that CBD binds to the undertwisted region of the minicollagen but does not actively unwind the triple helix.
Asenapine (Sycrest): sublingual antipsychotic for acute mania
Authors: Chaplin Steve , Smith Daniel
Published: August 2012

Asenapine (Sycrest) is an antipsychotic taken sub ‐ lingually for the treatment of moderate to severe manic episodes in bipolar disorder. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse events and Dr Daniel Smith discusses its place in therapy. Copyright © 2012 Wiley Interface Ltd
Concise guide to management of reflux disease in primary care
Authors: Basu Kumar Kanti
Published: August 2012

Reflux is a common disorder often aggravated by lifestyle and other medications. Our Drug review discusses the symptoms, pathophysiology, investigations and drug therapy of GORD, followed by a review of the prescription data and sources of further information. Copyright © 2012 Wiley Interface Ltd
The Immunosuppressive Activity of Pseudolaric Acid B on T lymphocytes in vitro
Authors: Wei Na , Li Tan , Chen Hong , Mei Xin , Cao Bo , Zhang Yu‐yang
Published: August 2012

Pseudolaric acid B (PB) is a major bioactive component extracted from Pseudolarix kaempferi. Traditional medicine practitioners in China have been using the roots of this plant to treat inflammatory and microbial dermatoses for centuries. In this study, the experiments were conducted to investigate immunosuppressive activity of PB on T lymphocytes in vitro. The results show that PB has hypotoxicity on hepatocytes and renal cells assessed by Methyl thiazolyl tetrazoliym (MTT) Assay and selectively inhibits the proliferation of T lymphocytes and antigen‐specific T lymphocytes stimulated by concanavalin A and dinitrophenyl‐modified spleen cells, respectively. Then, PB also shows suppressive effect on T lymphocytes in mixed lymphocyte reaction. Moreover, PB can depress the production of interleukin‐2 (IL‐2) secreted by concanavalin A‐activated T lymphocytes or dinitrophenyl‐modified spleen cells‐activated antigen‐specific T lymphocytes. It is first found that PB exhibits the inhibitory action on antigen‐specific T lymphocytes and on the production of IL‐2 from antigen‐specific T lymphocytes and selectively inhibits the proliferation of T lymphocytes and the production of IL‐2 as well. PB is in need of further study because of its potent immunosuppressive function. Copyright © 2012 John Wiley & Sons, Ltd.
Resolution of sharp fronts in the presence of model error in variational data assimilation
Authors: Freitag M. A. , Nichols N. K. , Budd C. J.
Published: August 2012

We show that the four‐dimensional variational data assimilation method (4DVar) can be interpreted as a form of Tikhonov regularization, a very familiar method for solving ill‐posed inverse problems. It is known from image restoration problems thatL1‐norm penalty regularization recovers sharp edges in the image more accurately than Tikhonov, orL2‐norm, penalty regularization. We apply this idea from stationary inverse problems to 4DVar, a dynamical inverse problem, and give examples for anL1‐norm penalty approach and a mixed total variation (TV)L1–L2‐norm penalty approach. For problems with model error where sharp fronts are present and the background and observation error covariances are known, the mixed TVL1–L2‐norm penalty performs better than either theL1‐norm method or the strong‐constraint 4DVar (L2‐norm) method. A strength of the mixed TVL1–L2‐norm regularization is that in the case where a simplified form of the background error covariance matrix is used it produces a much more accurate analysis than 4DVar. The method thus has the potential in numerical weather prediction to overcome operational problems with poorly tuned background error covariance matrices. Copyright © 2012 Royal Meteorological Society
A non‐iterative implementation of Tango's score confidence interval for a paired difference of proportions
Authors: Yang Zhao , Sun Xuezheng , Hardin James W.
Published: August 2012

For matched‐pair binary data, a variety of approaches have been proposed for the construction of a confidence interval (CI) for the difference of marginal probabilities between two procedures. The score‐based approximate CI has been shown to outperform other asymptotic CIs. Tango's method provides a score CI by inverting a score test statistic using an iterative procedure. In this paper, we propose an efficient non‐iterative method with closed‐form expression to calculate Tango's CIs. Examples illustrate the practical application of the new approach. Copyright © 2012 John Wiley & Sons, Ltd.
The Role of Mentoring in Supporting Novice English Language Teachers in Hong Kong
Authors: Mann Steve , Tang Elaine Hau Hing
Published: August 2012

This article reports on qualitative case study research into the experience and support of four novice English language teachers in Hong Kong (HK). It describes their perceived experience and socialisation, particularly with regard to the induction and mentoring support they receive during the first year of teaching. While the benefits of different forms of induction support (mentoring in particular) have been established, few studies have focused on specific factors that affect the perceived effectiveness of mentoring, from the point of view of both the mentors and the mentees. The current study therefore breaks new ground in investigating the perspectives of different stakeholders in the mentoring process. What is more, the majority of research reports the nature of the first year of teaching in one snapshot, often not paying attention to the professional development and changes throughout the year. This study follows a group of novice language teachers for the whole of their first year in teaching.
“It Cannot Be Done Alone”: The Socialization of Novice English Teachers in South Korea
Authors: Shin Sang‐Keun
Published: August 2012

Prior studies on novice teachers' adjustment to the school environment have shown that many new teachers adopt the teaching practices of existing teachers. By exploring the reasons why new teachers with a proficient command of English end up conducting English classes in Korean, this study analyzed factors influencing the socialization of new teachers. Analyses of questionnaires, interviews, and critical incident reports show that the choice of instructional language was influenced by institutional constraints, school culture, and norms surrounding the teaching and learning of English, rather than the teacher's individual capabilities. The results suggest that a more important factor than the individual teacher's ability is creating school systems and school cultures that enable teachers to apply the teaching methods they were trained to use.
Post‐translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding
Authors: Prabakaran Sudhakaran , Lippens Guy , Steen Hanno , Gunawardena Jeremy
Published: August 2012

We discuss protein post‐translational modification (PTM) from an information processing perspective. PTM at multiple sites on a protein creates a combinatorial explosion in the number of potential ‘mod‐forms’, or global patterns of modification. Distinct mod‐forms can elicit distinct downstream responses, so that the overall response depends partly on the effectiveness of a particular mod‐form to elicit a response and partly on the stoichiometry of that mod‐form in the molecular population. We introduce the ‘mod‐form distribution’—the relative stoichiometries of each mod‐form—as the most informative measure of a protein's state. Distinct mod‐form distributions may summarize information about distinct cellular and physiological conditions and allow downstream processes to interpret this information accordingly. Such information ‘encoding’ by PTMs may facilitate evolution by weakening the need to directly link upstream conditions to downstream responses. Mod‐form distributions provide a quantitative framework in which to interpret ideas of ‘PTM codes’ that are emerging in several areas of biology, as we show by reviewing examples of ion channels, GPCRs, microtubules, and transcriptional co‐regulators. We focus particularly on examples other than the well‐known ‘histone code’, to emphasize the pervasive use of information encoding in molecular biology. Finally, we touch briefly on new methods for measuring mod‐form distributions. WIREs Syst Biol Med 2012, 4:565–583. doi: 10.1002/wsbm.1185

This article is categorized under:

Models of Systems Properties and Processes > Mechanistic Models

Laboratory Methods and Technologies > Proteomics Methods

Biological Mechanisms > Regulatory Biology
Population pharmacokinetic modeling of Sepantronium bromide (YM155), a small molecule survivin suppressant, in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma
Authors: Aoyama Yumiko , Kaibara Atsunori , Takada Akitsugu , Nishimura Tetsuya , Katashima Masataka , Sawamoto Taiji
Published: August 2012

Purpose Population pharmacokinetics (PK) of sepantronium bromide (YM155) was characterized in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma and enrolled in one of three phase 2 studies conducted in Europe or the U.S. Method Sepantronium was administered as a continuous intravenous infusion (CIVI) at 4.8 mg/m2/day over 7 days every 21 days. Population PK analysis was performed using a linear one-compartment model involving total body clearance (CL) and volume of distribution with an inter-individual random effect on CL and a proportional residual errors to describe 578 plasma sepantronium concentrations obtained from a total of 96 patients by NONMEM Version VI. The first-order conditional estimation method with interaction was applied. Results The one-compartment model with one random effect on CL and two different proportional error models provided an adequate description of the data. Creatinine clearance (CLCR), cancer type, and alanine aminotransferase (ALT) were recognized as significant covariates of CL. CLCR was the most influential covariate on sepantronium exposure and predicted to contribute to a 25 % decrease in CL for patients with moderately impaired renal function (CLCR = 40 mL/min) compared to patients with normal CLCR. Cancer type and ALT had a smaller but nonetheless significant contribution. Other patient characteristics such as age, gender, and race were not considered as significant covariates of CL. Conclusions The results provide the important information for optimizing the therapeutic efficacy and minimizing the toxicity for sepantronium in cancer therapy.
Unintended Diagnosis of Von Hippel Lindau Syndrome Using Array Comparative Genomic Hybridization (CGH): Counseling Challenges Arising from Unexpected Information
Authors: Hogan Jennifer , Turner A. , Tucker K. , Warwick L.
Published: August 2012

Array Comparative Genomic Hybridization (array CGH) is a powerful tool for identifying genomic imbalances and providing a diagnosis in individuals with a normal karyotype. It has been particularly useful in the investigation of individuals with developmental delay +/−, dysmorphic features and/or multiple congenital abnormalities. However, this non‐targeted method of scanning the whole genome can reveal unexpected information. We present a case where array CGH identified the cause of a proband's moderate mental retardation by discovery of a de novo deletion of chromosome 3p25.3. This deletion was shown to contain at least 25 genes including the VHL gene, the deletion or mutation of which leads to Von Hippel Lindau (VHL) syndrome. Presymptomatic testing for VHL is usually offered after appropriate genetic counseling about the implications of this condition. Therefore, scanning the genome by array CGH presents a number of challenges for the genetic counselor. We suggest that further understanding of the psychosocial effects of array CGH is needed in order for appropriate pre‐ and post‐test counseling to be provided.
Bronze- and Iron-Age Celtic-speakers: what don't we know, what can't we know, and what could we know? Language, genetics and archaeology in the twenty-first century
Authors: Sims-Williams Patrick
Published: August 2012

In 1998 the author published ‘Genetics, linguistics and prehistory: thinking big and thinking straight’, a critique of late twentieth-century attempts to synthesize the disciplines of genetics, linguistics and archaeology. This paper assesses subsequent progress, using examples from various parts of the world, including Britain, Denmark, Finland, France, Frisia, Germany, Hungary, Ireland, Italy, Micronesia, Portugal, Spain and the Canary Islands. The growing importance of mitochondrial DNA and the Y chromosome, rather than classical population genetics, is emphasized. The author argues that ancient DNA and early linguistic data should be used more. Languages mentioned include Aquitanian, Basque, Celtiberian, Etruscan, Finnish, Hungarian, Iberian, Lepontic, Lusitanian, Pictish, Raetic, ‘Tartessian’, Thracian and the Ladin dialect of the Italian Alps. Aspects of the ancient linguistic geography of Scotland and the Iberian peninsula are discussed, as is the difficulty of deciding the direction of spread of Indo-European and non-Indo-European languages. The potential of ancient place and personal names is illustrated from Celtic.
Colonial Township Laws and Urban Governance in Kenya
Authors: Home Robert
Published: August 2012

Rapid population and urban growth in Africa pose severe challenges to development planning and management. This article argues that weak urban governance in Kenya results from the colonial legal order's shaping of urban form. Kenya's colonial laws, drawing from those in other British colonies (especially South Africa) and British statute law on local government, public health, housing and town planning, controlled African labour and movement, and Africans' relation to towns. These laws included ordinances on registration, “master and servant” and vagrancy, while detailed township rules enforced racial segregation and exclusion; the Feetham Commission (1926) led to a hierarchy of local authorities, with no African representation until the 1950s. The dual mandate ideology resulted in different land tenure in the white-settled areas and trust lands; the late introduction of individual land ownership in the trust lands created problems of peri-urban, unplanned development outside the old township boundaries.
Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverriniin vitro and in vivo
Authors: Keiser J. , Adelfio R. , Vargas M. , Odermatt P. , Tesana S.
Published: August 2012

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine–praziquantel combinations against O. viverriniin vitro and in vivo. The IC50 values of 0.16 μg/ml and 0.05 μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverriniin vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38–62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini.
Significance of a notch in the otoacoustic emission stimulus spectrum
Authors: Grenner J
Published: August 2012

Objective:

To explain a clinical observation: a notch in the stimulus spectrum during transient evoked otoacoustic emission measurement in ears with secretory otitis media.

Methods:

The effects of tympanic under-pressure were investigated using a pressure chamber. A model of the ear canal was also studied.

Results:

Tympanic membrane reflectance increased as a consequence of increased stiffness, causing a notch in the stimulus spectrum. In an adult, the notch could be clearly distinguished at an under-pressure of approximately −185 daPa. The sound frequency of the notch corresponded to a wavelength four times the ear canal length. The ear canal of infants was too short to cause a notch within the displayed frequency range. The notch was demonstrated using both Otodynamics and Madsen equipment.

Conclusion:

A notch in the otoacoustic emission stimulus spectrum can be caused by increased stiffness of the tympanic membrane, raising suspicion of low middle-ear pressure or secretory otitis media. This finding is not applicable to infants.
Speech in noise testing before and after grommet insertion
Authors: Possamai V , Kirk G , Scott A , Skinner D
Published: August 2012

Objectives:

To assess the feasibility of designing and implementing a speech in noise test in children before and after grommet insertion, and to analyse the results of such a test in a small group of children.

Methods:

Twelve children aged six to nine years who were scheduled to undergo grommet insertion were identified. They underwent speech in noise testing before and after grommet insertion. This testing used Arthur Boothroyd word lists read at 60 dB in four listening conditions presented in a sound field: firstly in quiet conditions, then in signal to noise ratios of +10 (50 dB background noise), 0 (60 dB) and −10 (70 dB).

Results:

Mean phoneme scores were: in quiet conditions, 28.1 pre- and 30 post-operatively (p = 0.04); in 50 dB background noise (signal to noise ratio +10), 24.2 pre- and 29 post-operatively (p < 0.01); in 60 dB background noise (signal to noise ratio 0), 22.6 pre- and 27.5 post-operatively (p = 0.06); and in 70 dB background noise (signal to noise ratio −10), 13.9 pre- and 21 post-operatively (p = 0.05).

Conclusion:

This small study suggests that speech in noise testing is feasible in this scenario. Our small group of children demonstrated a significant improvement in speech in noise scores following grommet insertion. This is likely to translate into a significant advantage in the educational environment.
Use of personal call alarms among community-dwelling older people
Authors: NYMAN SAMUEL R. , VICTOR CHRISTINA R.
Published: August 2012

Having a fall and then lying on the floor for an hour or more is known as a ‘long lie’, which is associated with serious injury and an elevated risk of admission to hospital, long-term care and death. Personal call alarms are designed to prevent long lies, although little is known about their use. Using cross-sectional data from the English Longitudinal Study on Ageing, this study investigated the proportion of self-reported users of personal call alarms among 3,091 community-dwelling adults aged 65+ who reported difficulties of mobility or activities of daily living. The characteristics of users were then explored through logistic regressions comparing those living alone with those living with others. One hundred and eighty people self-reported using a personal call alarm (6%). Multivariate regression found the following to significantly predict personal call alarm use among both those living alone and with others: greater difficulty with activities/instrumental activities of daily living, older age, and for those living with others only: lower score on the quality of life subscale for control. Personal call alarm use may be markedly lower than the 30 per cent annual incidence of falls among community-dwelling older people. Better understanding is needed of the reasons for low usage, even amongst those at highest falls risk for whom such alarms are most likely to be beneficial.
PROMPT-TYPE FREQUENCY, AUDITORY PATTERN DISCRIMINATION, AND EFL LEARNERS’ PRODUCTION OFWH-QUESTIONS
Authors: McDonough Kim , De Vleeschauwer Jindarat
Published: August 2012

Recently researchers have suggested that syntactic priming may facilitate the production ofwh-questions with obligatory auxiliary verbs, particularly when learners are prompted to produce those questions with a wide variety of lexical items (McDonough & Kim, 2009; McDonough & Mackey, 2008). However, learners’ ability to benefit from syntactic priming materials with prompt-type frequency may be mediated by their ability to recognize patterns in aural input. The purpose of this replication study is to confirm the positive impact of prompt-type frequency on learners’ production ofwh-questions reported by McDonough and Kim (2009), and to investigate whether its impact is mediated by learners’ auditory pattern-discrimination abilities. Thai learners (n= 43) of English as a foreign language (EFL) carried out three oral tests, two sets of syntactic priming activities, and an auditory pattern-discrimination test over a 4-week period. Half of the learners carried out the syntactic priming activities with low-type-frequency prompts, whereas the other learners received high-type-frequency prompts. The results revealed a significant interaction between Type Frequency × Auditory Pattern Discrimination on the immediate and delayed posttests. The findings are discussed in terms of the potential role of individual cognitive factors in mediating the relationship between syntactic priming and second language (L2) development.
Quantitative exposure assessment of waterfowl hunters to avian influenza viruses
Authors: DÓREA F. C. , COLE D. J. , STALLKNECHT D. E.
Published: August 2012

The potential for direct transmission of type A influenza viruses from wild waterfowl to humans is undefined. This study estimated exposure of hunters to avian influenza virus (AIV) resulting from direct contact with potentially infected waterfowl in Georgia (GA), Louisiana (LA) and Minnesota (MN), and demonstrated variation in the risk of exposure to AIV by hunting location and time. Hunting begins earlier in MN, starting in October, and later in GA and LA, usually starting in November. In addition, the numbers of hunters and birds harvested varies considerably in each state, with LA hosting the largest harvest in the USA Temporal effects resulted in variation of the exposure risk per hunter-day, with a higher risk associated with the earlier months of the hunting season. Exposure risk in locations varied due to AIV prevalence during each hunting season, average bird harvest per hunter-day, and ratio of juveniles/adult birds harvested (higher risk associated with higher ratios). Population risk is discussed based on the exposure risk and number of active hunters in each state per month. The risk of human exposure to AIV was also shown to be temporally distinct from the time of greatest risk of human influenza A infection during circulation of seasonal human influenza viruses, making recombination events due to co-infection unlikely.