bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of constitutively activated phosphoinositide 3‐kinase/AKT pathway enhances antitumor activity of chemotherapeutic agents in breast cancer susceptibility gene 1‐defective breast cancer cells
Authors: Yi Yong Weon , Kang Hyo Jin , Kim Hee Jeong , Hwang Jae Seok , Wang Antai , Bae Insoo
Published: April 2012

Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1‐defective human breast cancer cells. Levels of phospho‐AKT are sustained even after serum starvation in breast cancer cells carrying deleterious BRCA1 mutations. Knockdown of BRCA1 in MCF7 cells increases the amount of phospho‐AKT and sensitizes cells to small molecule protein kinase inhibitors (PKIs) targeting the PI3K/AKT pathway. Restoration of wild type BRCA1 inhibits the activated PI3K/AKT pathway and de‐sensitizes cells to PKIs targeting this pathway in BRCA1 mutant breast cancer cells, regardless of PTEN mutations. In addition, clinical PI3K/mTOR inhibitors, PI‐103, and BEZ235, showed anti‐proliferative effects on BRCA1 mutant breast cancer cell lines and synergism in combination with chemotherapeutic drugs, cisplatin, doxorubicin, topotecan, and gemcitabine. BEZ235 synergizes with the anti‐proliferative effects of gemcitabine by enhancing caspase‐3/7 activity. Our results suggest that the PI3K/AKT pathway can be an important signaling pathway for the survival of BRCA1‐defective breast cancer cells and pharmacological inhibition of this pathway is a plausible treatment for a subset of breast cancers. © 2012 Wiley Periodicals, Inc.
Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A ‘Piggyback’ Approach for Antimalarial Drug Discovery
Authors: Sreshty M. Asha Latha , Surolia Avadhesha , Sastry G. Narahari , Murty U. Suryanarayana
Published: April 2012

Quest for new drug targets in Plasmodium sp. has underscored malonyl CoA:ACP transacylase (PfFabD) of fatty acid biosynthetic pathway in apicoplast. In this study, a “piggyback” approach was employed for the receptor deorphanization using inhibitors of bacterial FabD enzymes. Due to the lack of crystal structure, theoretical model was constructed using the structural details of homologous enzymes. Sequence and structure analysis has localized the presence of two conserved pentapeptide motifs: GQGXG and GXSXG and five key invariant residues viz., Gln109, Ser193, Arg218, His305 and Gln354 characteristic of FabD enzyme. Active site mapping of PfFabD using substrate molecules has disclosed the spatial arrangement of key residues in the cavity. As structurally similar molecules exhibit similar biological activities, signature pharmacophore fingerprints of FabD antagonists were generated using 0D‐3D descriptors for molecular similarity‐based cluster analysis and to correlate with their binding profiles. It was observed that antagonists showing good geometrical fitness score were grouped in cluster‐1, whereas those exhibiting high binding affinities in cluster‐2. This study proves important to shed light on the active site environment to reveal the hotspot for binding with higher affinity and to narrow down the virtual screening process by searching for close neighbors of the active compounds.
Multiple Kernel Learning for Drug Discovery
Authors: Pilkington Nicholas C. V. , Trotter Matthew W. B. , Holden Sean B.
Published: April 2012

The support vector machine (SVM) methodology has become a popular and well‐used component of present chemometric analysis. We assess a relatively recent development of the algorithm, multiple kernel learning (MKL), on published structure‐property relationship (SPR) data. The MKL algorithm learns a weighting across multiple kernel‐based representations of the data during supervised classifier creation and, thereby, may be used to describe the influence of distinct groups of structural descriptors upon a single structure–property classifier without explicitly omitting any of them. We observe a statistically significant performance improvement over a conventional, single kernel SVM on all three SPR data sets analysed. Furthermore, MKL output is observed to provide useful information regarding the relative influence of five distinct descriptor subsets present in each data set.
Generative Topographic Mapping (GTM): Universal Tool for Data Visualization, Structure‐Activity Modeling and Dataset Comparison
Authors: Kireeva N. , Baskin I. I. , Gaspar H. A. , Horvath D. , Marcou G. , Varnek A.
Published: April 2012

Here, the utility of Generative Topographic Maps (GTM) for data visualization, structure‐activity modeling and database comparison is evaluated, on hand of subsets of the Database of Useful Decoys (DUD). Unlike other popular dimensionality reduction approaches like Principal Component Analysis, Sammon Mapping or Self‐Organizing Maps, the great advantage of GTMs is providing data probability distribution functions (PDF), both in the high‐dimensional space defined by molecular descriptors and in 2D latent space. PDFs for the molecules of different activity classes were successfully used to build classification models in the framework of the Bayesian approach. Because PDFs are represented by a mixture of Gaussian functions, the Bhattacharyya kernel has been proposed as a measure of the overlap of datasets, which leads to an elegant method of global comparison of chemical libraries.
A method based on meshless approach for the numerical solution of the two‐space dimensional hyperbolic telegraph equation
Authors: Dehghan Mehdi , Salehi Rezvan
Published: April 2012

In the current article, we investigate the RBF solution of second‐order two‐space dimensional linear hyperbolic telegraph equation. For this purpose, we use a combination of boundary knot method (BKM) and analog equation method (AEM). The BKM is a meshfree, boundary‐only and integration‐free technique. The BKM is an alternative to the method of fundamental solution to avoid the fictitious boundary and to deal with low accuracy, singular integration and mesh generation. Also, on the basis of the AEM, the governing operator is substituted by an equivalent nonhomogeneous linear one with known fundamental solution under the same boundary conditions. Finally, several numerical results and discussions are demonstrated to show the accuracy and efficiency of the proposed method. Copyright © 2012 John Wiley & Sons, Ltd.
Reliability and validity of the overactive bladder symptom score in spanish (OABSS‐S)
Authors: Weinberg Aaron C. , Brandeis Gary H. , Bruyere John , Tsui Johnson F. , Weiss Jeffrey P. , Rutman Matthew P. , Blaivas Jerry G.
Published: April 2012

Purpose

To validate the Spanish translation of the Overactive Bladder Symptom Score (OABSS) questionnaire.

Materials and Methods

The OABSS was translated into Spanish (OABSS‐S) and back translated. The OABSS‐S was self‐administered to subjects, following internal IRB and ISPOR Good Practices guidelines. Spanish speaking patients >18 years of age were recruited from primary care clinics. Content validity was achieved by having the first 25 subjects complete the questionnaire in privacy; afterwards they were interviewed and the clarity of each question was discussed with the patient. All subjects recruited, including the first 25, were divided into two groups by the presence of OAB as determined by a previously validated intake question. Subjects completed the OABSS‐S in privacy on two occasions within 10 days. Patients were excluded if their symptoms changed between the first and second administration of the questionnaire. Internal consistency was determined with Cronbach's alpha. Test–retest was determined by Spearman's rho. Discriminant validity was assessed between each group using one‐way ANOVA and the Tukey post hoc test.

Results

One hundred and seventeen of 128 enrolled subjects completed this study (mean age 55; SD 18). Of 117, 74 (63%) were women 29 with OAB and 45 without OAB. There were 43 men (37%), 18 with OAB and 25 without OAB. A high level of consistency was observed among the seven items answered at visit 1 and 2, with a Cronbach's raw alpha statistic of 0.92. No differences in OABSS‐S with age or gender were noted. However, subgroup analysis showed patients in the OAB group were significantly older and post‐test analysis showed they had higher scores both for each individual question as well as overall symptom severity scores. Spearman's rank order correlation coefficients showed that there was significant difference between the seven items of the OABSS‐S; a strong association (Spearman's rho) was also observed between the total seven‐item score at visits 1 and 2 for the total score of all subjects r = 0.84, with OAB: r = 0.81, and without OAB: r = 0.83. Comparison of average total scores obtained for all patients at visits 1 and 2 was not significant (10.47 ± 6.53 vs. 11.02 ± 0.66). Discriminant validity testing revealed that there were significant differences in the responses between all diagnostic groups at visits 1 and 2: with OAB versus without OAB; total versus with OAB; total versus without OAB.

Conclusion

The Spanish version of the OABSS is valid and reliable and will allow health care providers to easily and quickly assess a Spanish‐speaking patient's symptoms. Neurourol. Urodynam. 31:664–668, 2012. © 2012 Wiley Periodicals, Inc.
Modification of poly(vinyl alcohol) films by the addition of magnesium chloride hexahydrate
Authors: Jiang Xiancai , Zhang Xiaofei , Ye Dezhan , Zhang Xi , Dai Hua
Published: April 2012

Poly(vinyl alcohol) (PVA) films modified with Magnesium chloride hexahydrate (MgCl2·6H2O) were prepared by casting method. The prepared films were characterized by X‐ray diffraction measurements (XRD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and mechanical testing. It was found that the presence of MgCl2·6H2O had considerable effects on the crystallinity, thermal, and mechanical properties of PVA films. The crystallization of PVA film was interrupted and the degree of crystallinity of PVA film decreased with the addition of MgCl2·6H2O. The glass transition temperature of PVA film decreased with the addition of MgCl2·6H2O. After modifying with MgCl2·6H2O, PVA film became soft, with lower tensile strength and higher elongation at break. The presence of MgCl2·6H2O could significantly increase the moisture content of PVA films and this may be the cause of the plasticizing. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Central small‐angle diffuse scattering from fibers is made of two components
Authors: Wang Wenjie , Murthy N. Sanjeeva , Grubb David T.
Published: April 2012

Small‐angle X‐ray and neutron scattering from materials with fibrous texture generally includes a central diffuse scattering that is either diamond‐shaped or shaped like a two‐bladed propeller. The central scattering from fibers of polyacrylonitrile, nylon, and poly(ethylene terephthalate) and in particular the changes seen during deformation and heating have been examined. The result is that all types of central scattering from fibers are best described as having two distinct components, where these components are an extended equatorial streak and an inner nearly isotropic scattering. They arise respectively from objects that do and do not become aligned or elongated during fiber production. Examples of objects that do not become aligned are small spherical voids and solid particles. Objects that do become aligned include internal phase boundaries, and the surfaces of the fibers themselves. The equatorial streak arises from an assembly of such elongated objects preferentially oriented along the fiber axis. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Light to work transduction and shape memory in glassy, photoresponsive macromolecular systems: Trends and opportunities
Authors: White Timothy J.
Published: April 2012

Light can wirelessly direct functional responses in photoresponsive polymeric materials and composites. The intensity, phase, and polarization of light can be spatially modulated into complex patterns with holography (intensity or polarization) or masking (intensity or phase). Deriving from these foundational properties of light, photoresponsive macromolecular systems exhibit exceeding potential to yield rapid and highly engineered macroscopic as well as spatially selectable mechanically adaptive responses useful as soft actuators or topographical surfaces in aerospace, automotive, and biomedical applications. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Estimating Ambient Vapor Pressures of Low Volatility Explosives by Rising‐Temperature Thermogravimetry
Authors: Brady Joseph E. , Smith James L. , Hart Casuarina E. , Oxley Jimmie
Published: April 2012

Vapor pressure is a fundamental physical characteristic of chemicals. Some solids have very low vapor pressures. Nevertheless numerous chemical detection instruments aim to detect vapors. Herein we address issues with explosive detection and use thermogravimetric analysis (TGA) to estimate vapor pressures. Benzoic acid, whose vapor pressure is well characterized, was used to calculate instrumental parameters related to sublimation rate. Once calibrated, the rate of mass loss from TGA measurements was used to obtain vapor pressures of the 12 explosives at elevated temperature: explosive salts – guanidine nitrate (GN); urea nitrate (UN); ammonium nitrate (AN); as well as mono‐molecular explosives – hexanitrostilbene (HNS); cyclotetramethylene‐tetranitramine (HMX), 4,10‐dinitro‐2,6,8,12‐tetraoxa‐4,10‐diaza‐tetracyclododecane (TEX), cyclotrimethylenetrinitramine (RDX), pentaerythritol tetranitrate (PETN), 3‐nitro‐1,2,4‐triazol‐5‐one (NTO), 1,3,3‐trinitroazeditine (TNAZ), triacetone triperoxide (TATP), and diacetone diperoxide (DADP). Ambient temperature vapor pressures were estimated by extrapolation of Clausius‐Clapeyron plots (i.e. ln p vs. 1/T). With this information potential detection limits can be assessed.
Salts of Tetrazolone – Synthesis and Properties of Insensitive Energetic Materials
Authors: Fischer Dennis , Klapötke Thomas M. , Stierstorfer Jörg
Published: April 2012

Tetrazolone (5‐oxotetrazole, 1) is formed by diazotization of 5‐aminotetrazole in the presence of CuSO4. Nitrogen‐rich salts such as guanidinium (2), 1‐aminoguanidinium (3), 1,3‐diamino‐guanidinium (4), 1,3,5‐triamino‐guanidinium (5), ammonium (6), hydrazinium (7) and the hydroxylammonium (8) salts of tetrazolone were prepared by facile deprotonation or metathesis reactions. All compounds were characterized by single‐crystal X‐ray diffraction, vibrational spectroscopy (IR and Raman), multinuclear NMR spectroscopy, elemental analysis and DSC measurements. The heats of formation of 2–8 were calculated using the atomization method based on CBS‐4M enthalpies. With these values and the experimental (X‐ray) densities several detonation parameters such as the detonation pressure, velocity, energy and temperature were computed using the EXPLO5 code (V.5.04). In addition, the sensitivities towards impact, friction and electrical discharge were tested using the BAM drop hammer and friction tester as well as a small scale electrical discharge device.
Chemoaffinity capture of pre‐targeted prostate cancer cells with magnetic beads
Authors: Wu Lisa Y. , Liu Tiancheng , Hopkins Mark R. , Davis William C. , Berkman Clifford E.
Published: April 2012

BACKROUND

Prostate circulating tumor cells (PCTCs) in circulation are shed from either a primary tumor or metastases, which are directly responsible for most prostate cancer deaths. Quantifying exfoliated PCTCs may serve as an indicator for the clinical management of prostate cancer, isolating and removing of PCTCs could potentially reduce prostate cancer metastasis, and culturing and characterizing captured PCTCs could facilitate the development of personalized treatment options. Prostate‐specific membrane antigen (PSMA) is an established biomarker for prostate cancer being strongly expressed on prostate tumor cells associated with high‐grade primary, androgen independent, and metastatic tumors.

METHODS

Suspensions of PSMA+ (LNCaP) cells were pre‐targeted with the irreversible PSMA inhibitor biotin‐PEG12‐CTT‐54 to serve as a bait to capture PSMA+ cells using streptavidin‐coated magnetic beads. Decreasing numbers of LNCaP cells were spiked into blood to determine the cell captured efficiency, recovery and viability.

RESULTS

High selectivity, recovery, and viability were achieved for the capture of PSMA+ cells in both model experiments with mixtures of LNCaP cells and WBCs as well as blood samples spiked with LNCaP cells. As low as 10 cells were captured from 1 ml of blood with nearly 90% viability. More importantly, captured cells could be subsequently propagated in vitro.

CONCLUSIONS

This methodology for the detection, isolation, and culture of PCTCs from peripheral blood can serve as an effective tool for the detection of metastatic prostate cancer, treatment monitoring, and the development of personalized therapy based on the responsiveness of PCTCs to chemotherapeutic strategies. Prostate 72:1532–1541, 2012. © 2012 Wiley Periodicals, Inc.
Excitation effects and luminescence stability in porous SiO2:C layers
Authors: Vasin Andriy , Rusavsky Andriy , Nazarov Alexei , Lysenko Vladimir , Rudko Galyna , Piryatinski Yurii , Blonsky Ivan , Salonen Jarno , Makila Ermei , Starik Sergii
Published: April 2012

White‐light emitting porous SiO2:C layers on silicon wafers have been fabricated by oxidation of carbonized porous silicon. The study was focused mainly on the identification of the mechanism of light emission and photo‐induced degradation. The effect of carbonization temperature and exposure to intense ultraviolet irradiation on the photoluminescence (PL) properties was studied by steady state and time‐resolved PL measurements. Two types of photo‐induced degradation phenomena were observed: reversible and irreversible. The irreversible degradation is suggested to be associated with photo‐induced chemical interaction of light emitting material with atmospheric oxygen. It is demonstrated that irreversible degradation can be reduced by encapsulation of the light‐emitting material. The structural configuration of light‐emitting centers and mechanism of reversible degradation are discussed.
Improved photoluminescence of red‐emitting NaCaPO4:Eu3+ phosphor by charge compensation
Authors: Chen Li , Hui Zhang Zhan , Tong Chun , Fu Cheng De , Liang Huang Zhi
Published: April 2012

In this paper, we report the preparation of a red‐emitting NaCaPO4:Eu3+ phosphor by the solid‐state method at 900 °C, also the effects of Eu3+ concentration on its luminescent properties were investigated. To achieve charge compensation, additional Na+ acting as a charge compensator was incorporated into the phosphor. Under near‐ultraviolet (UV) excitation, the luminescent properties as a function of additional Na+ concentration were systematically studied with a fixed optimal Eu3+ concentration. It was found that charge‐compensated phosphors showed greatly enhanced red emission at 619 nm, compared with the phosphor without charge compensation. Na1.3Ca0.4PO4:0.3Eu3+ was deduced to be the best composition and its luminescent intensity was stronger than that of commercial red‐emitting phosphors for white light‐emitting diode application.

magnified image

The emission spectra of as‐prepared NaCa0.7PO4:0.3Eu3+ (a), Na1.3Ca0.4PO4:0.3Eu3+ (b), and commercial Y2O2S:Eu3+ (c) phosphors excited by 395 nm.
Investigation of the stability of boron‐doped zinc oxide films grown by low‐pressure chemical vapor deposition
Authors: Zhu H. , Feng Y. , Zhang L. , Lai B. , He T. , Liu D. , Wang Y. , Yin J. , Ma Y. , Huang Y. , Jia H. , Mai Y.
Published: April 2012

The stability of transparent conductive oxide (TCO) films of silicon thin‐film solar cells is important to the device performance. As an important TCO material, the boron‐doped zinc oxide (ZnO:B) films are grown by a low‐pressure chemical vapor deposition (LPCVD) technique. The stability of ZnO:B films with different doping levels is systematically investigated through a post‐thermal treatment at temperatures of 300 and 250 °C for different durations. In addition, the variations of optical and electrical properties of ZnO:B films after a damp‐heat treatment are studied as well. It is found that the stability of the ZnO:B films with a high doping level is better compared to lowly doped ZnO:B films. Moreover, the total transmission (TT) in the near‐infrared (NIR) wavelength range increases with increasing temperature and duration of the thermal treatment. With the increasing damp‐heat exposure duration, the TT in the NIR wavelength range slightly increases while the sheet resistance increases up to three orders of magnitude. Such observations imply a higher degradation of carrier mobility than carrier density. Further, it is found that ZnO:B films, especially those with low doping levels, show an obvious degradation in electrical properties when they are stored in normal room ambient. All these discoveries will be a great help to the practical mass production of solar modules.
Band offsets of atomic layer deposited Al2O3 and HfO2 on Si measured by linear and nonlinear internal photoemission
Authors: Lei M. , Yum J. H. , Banerjee S. K. , Bersuker G. , Downer M. C.
Published: April 2012

We present measurements of band alignment of atomic layer deposited high‐k dielectrics on Si(100) using linear internal photoemission (IPE), detected by measuring photocurrent from a biased MOS capacitor, and internal multi‐photon photoemission (IMPE), detected by optical second‐harmonic generation (SHG). In IPE, Band offsets are extracted from either the threshold of quantum yield; in IMPE, they are determined by detecting discrete increments in multi‐photon order. IPE and IMPE yielded identical conduction band (CB) offsets (2.0 eV) for as‐deposited Si/Al2O3 structures with 10 and 3 nm oxides, respectively, in excellent agreement with previous measurements of annealed structures. Band offset measurements for Si/HfO2, on the other hand, show a strong (0.3 eV) upshift of the oxide valence band (VB) maximum, and an equal decrease of the oxide band gap upon post‐deposition annealing (PDA) at 600 °C, while the CB offset remains unchanged. We attribute the shift of the VB edge to thermally driven oxygen diffusion away from the Si/HfO2 interface.
Fractal dimension determined through optical and scanning electron microscopy on FeCrAl alloy after polishing, erosion, and oxidizing processes
Authors: Guzmán‐Castañeda J. I. , García‐Bórquez A. , Arizabalo‐Salas R. D.
Published: April 2012

Optical and scanning electron microscopy (OM and SEM) are techniques that are normally used for 2D‐analysis of surface features. By fractal dimension analysis of the gray‐scale OM and SEM images, it is possible to get quantitative topographical measurements. In this work, three different surface topographies (polished, eroded, and oxidized) were analyzed on FeCrAl alloy by OM and SEM. Clear surface topographical changes can be qualitatively observed. In order to quantify such changes, two steps were followed: (i) a gray‐scale digitalization from each image was used to reproduce topographical features on the analyzed surface, and (ii) from this information, the fractal dimension (D) was determined using fractal3e software. The fractal dimension determined in this form follows coherently the topographical changes produced on the FeCrAl alloy after polishing, erosion, and oxidizing processes. The variations of fractal dimension values against the temperature of the oxidizing processes reflect well the oxide growth changes. Moreover, a minimum D‐value is registered at 750 °C, which corresponds to the δ–θ alumina phase transition temperature as determined by differential thermal analysis (DTA) on the same alloy.
Mechanical properties of L12type Al3X (X = Mg, Sc, Zr) from first‐principles study
Authors: Fu Lin , Ke Jiang‐Ling , Zhang Quan , Tang Bi‐Yu , Peng Li‐Ming , Ding Wen‐Jiang
Published: April 2012

The mechanical properties of L12type Al3X (X = Mg, Sc, Zr) have been investigated by first‐principles calculations. The calculated elastic properties showed that Al3Sc was the stiffest and intrinsically brittle, while Al3Mg was the softest and exhibited ductility tendency. The obtained stress–strain curves demonstrated that both of the ideal tensile and shear strengths of Al3Zr were the strongest, followed by Al3Sc and Al3Mg, and Al3Zr was also the most ductile among three phases, which disagreed with the prediction from the calculated elastic properties, indicating that the mechanical properties should be measured from the complete stress–strain relations at both small and large strains. The electronic density of states (DOS) especially the variations of the charge density during the strain loading were investigated to unveil the intrinsic mechanism for the mechanical properties of L12type Al3X (X = Mg, Sc, Zr) phases.
Antitrypanosomal Properties of Panax ginseng C. A. Meyer: New Possibilities for a Remarkable Traditional Drug
Authors: Herrmann Florian , Sporer Frank , Tahrani Ahmad , Wink Michael
Published: April 2012

African trypanosomiasis is still a major health problem in many sub‐Saharan countries in Africa. We investigated the effects of three preparations of Panax ginseng, Panax notoginseng, isolated ginsenosides, and the polyacetylene panaxynol on Trypanosoma brucei brucei and the human cancer cell line HeLa. Hexane extracts and the pure panaxynol were toxic and at the same time highly selective against T. b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic and showed only weak selectivity. Panaxynol was cytotoxic against T. b. brucei at the concentration of 0.01 µg/mL with a selectivity index of 858, superior even to established antitrypanosomal drugs. We suggest that the inhibition of trypanothione reductase, which is only found in trypanosomes, might explain the observed selectivity. The high selectivity together with a cytotoxic concentration in the range of the bioavailability makes panaxynol and other polyacetylenes in general very promising lead compounds for the treatment of African trypanosomiasis. Copyright © 2012 John Wiley & Sons, Ltd.
Pancreatic Lipase Inhibitory Activity of Phlorotannins Isolated from Eisenia bicyclis
Authors: Eom Sung‐Hwan , Lee Myung‐Suk , Lee Eun‐Woo , Kim Young‐Mog , Kim Tae Hoon
Published: April 2012

Pancreatic lipase is a potential therapeutic target for the treatment of diet‐induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay‐guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7‐phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC50 values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 μM, respectively. Copyright © 2012 John Wiley & Sons, Ltd.
Probable polybasic residues inserted into the cleavage site of the highly pathogenic avian influenza A/H5N1 hemagglutinin: Speculation of the next outbreak in humans
Authors: Kaiyawet Nopporn , Rungrotmongkol Thanyada , Hannongbua Supot
Published: April 2012

The dissociation capability of the hemagglutinin precursor (HA0) to HA1 and HA2 is related to the degree of pathogenicity of influenza virus. The H5 strains that contain polybasic residues inserted at the cleavage site by the RXR/KR motif are recognized by the subtilisin‐like proteases and are associated with a high pathogenicity in humans. The available predicted amino acid sequences of the H5 subtype isolated from avian and human hosts were collected and aligned. As a result, most of the insertion types in viruses isolated from humans were also found in avian H5 isolates, but not in vice versa. With avian‐to‐human transmission, the unique avian H5 insertion types with the RXR/KR recognition motif were predicted as potential new candidates for the next highly pathogenic avian influenza H5 in humans. Additionally, at most the two basic residues extended from the recognition motif were found to be optimum fit with the furin‐like enzyme. © 2012 Wiley Periodicals, Inc.
The use of a membrane filtration device to form dried plasma spots for the quantitative determination of guanfacine in whole blood
Authors: Li Yuanyuan , Henion Jack , Abbott Richard , Wang Phillip
Published: April 2012

RATIONALE

A two‐layered polymeric membrane is employed for the formation of separated dried plasma spots from whole blood as an alternative to the direct analysis of whole dried blood spots (DBS). This dried plasma spot (DPS) analysis procedure precludes potential issues of hematocrit differences in whole blood samples while providing pharmokinetic data from plasma rather than whole blood. The described procedure is also semi‐automated thus providing a simpler work flow for LC/MS/MS bioanalysis procedures.

METHODS

Molecular filtration of red blood cells (RBC) from applied microsamples of whole blood fortified with guanfacine and its stable isotope internal standard was accomplished with a two‐layer polymeric membrane substrate. The lower membrane surface containing the separated plasma spot was physically separated from the upper membrane followed by semi‐automated direct elution of the sample to an online solid‐phase extraction (SPE) cartridge followed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS).

RESULTS

A two‐layer membrane sample preparation substrate produced plasma from whole blood without centrifugation which could be directly eluted for semi‐automated LC/MS/MS bioanalysis. Standard curves were constructed by plotting peak area ratios between the analyte and the stable isotope labeled internal standard (SIL‐IS) versus the nominal concentration in whole blood. A weighted 1/x2 linear regression was applied to the data from DPS samples. Standard curves were linear over the range 0.25–250 ng/mL human whole blood. The representative regression equation was y = 0.0142x + 0.00248 (R2 = 0.995) for the described DPS assay.

CONCLUSIONS

The described work demonstrates proof‐of‐principle using membrane sample preparation techniques to form DPS samples from whole blood for subsequent bioanalysis by LC/MS/MS. This approach has the potential to eliminate the hematocrit issues from the current controversy surrounding validation of DBS assays. Copyright © 2012 John Wiley & Sons, Ltd.
Searching for a subset of counterfeit coins: Randomization vs determinism and adaptiveness vs non‐adaptiveness
Authors: De Marco Gianluca , Kowalski Dariusz R.
Published: April 2012

We are given n coins of which k are heavy (defective), while the remaining n ‐ k are light (good). We know both the weight of the good coins and the weight of the defective ones. Therefore, if we weigh a subset Q ⊆ S with a spring scale, then the outcome will tell us exactly the number of defectives contained in Q. The problem, known as Counterfeit Coins problem, is to identify the set of defective coins by minimizing the number of weighings, also called queries. It is well known that Θ(klog k +1(n/k)) queries are enough, even for non‐adaptive algorithms, in case k ≤ cn for some constant 0 < c < 1.

A natural interesting generalization arises when we are required to identify any subset of m ≤ k defectives. We show that while for randomized algorithms
\documentclass{article}\usepackage{mathrsfs, amsmath, amssymb}\pagestyle{empty}\begin{document}\begin{align*}\tilde{\Theta}(m)\end{align*} \end{document}
queries are sufficient, the deterministic non‐adaptive counterpart still requires Θ(klog k +1(n/k)) queries, in case k ≤ n/28; therefore, finding any subset of defectives is not easier than finding all of them by a non‐adaptive deterministic algorithm. © 2012 Wiley Periodicals, Inc. Random Struct. Alg., 2012
Spillovers across organizational architectures: The role of prior resource allocation and communication in post‐acquisition coordination outcomes
Authors: Agarwal Rajshree , Anand Jaideep , Bercovitz Janet , Croson Rachel
Published: April 2012

We integrate insights from organization design, economic game theory, and social psychology to examine the role of prior resource allocation and communication in alleviating behavioral uncertainty arising in interunit coordination settings. We use the context of post‐acquisition coordination, focusing on the extent to which routines created under one organizational architecture (i.e., interorganizational alliances) may transfer to another organizational architecture (i.e., internal divisional structures via acquisition of alliance partners). Using a randomized experimental design, we find that prior resource allocation decisions in the absence of prior communication lowers post‐acquisition performance due to the development and transference of pre‐acquisition stage routines that may be inappropriate post‐acquisition. Post‐acquisition performance is aided, however, by the formation of noncompetitive routines in the pre‐acquisition stage in the presence of communication. Copyright © 2012 John Wiley & Sons, Ltd.
Structural knowledge: how executive experience with structural composition affects intrafirm mobility and unit reconfiguration
Authors: Karim Samina , Williams Charles
Published: April 2012

This article explores how knowledge embodied in executives is tied to the organizational context in which it develops. Drawing on the knowledge‐based view of the firm and human capital theory, we predict that executives will move between units with similar ‘structural composition’—a characteristic representing unit origin (as acquired or internally developed) and how the unit was reconfigured. We further argue that executives will be conduits of organizational change. We predict that units receiving more transferred executives, executives with recombination experience, and executives from core internal units will have a greater likelihood of being recombined, while units receiving executives from previously acquired units will tend to remain unchanged. The study examines a 20‐year panel of 48 multidivisional firms from the U.S. medical sector. Copyright © 2012 John Wiley & Sons, Ltd.
A Miniaturized Sensor Consisting of Concentric Metallic Nanorings on the End Facet of an Optical Fiber
Authors: Feng Shengfei , Darmawi Sabrina , Henning Torsten , Klar Peter J. , Zhang Xinping
Published: April 2012

A polarization‐independent optical sensor is created by fabricating a concentric gold ring grating with a period of 900 nm on the end facet of an optical fiber. The sensing function of this miniaturized device is realized by sending white light as a probe to the gold rings and collecting the response signal in the back‐reflection through the optical fiber. A pronounced peak due to the Rayleigh anomaly of the gold ring grating is observed in the reflection spectrum, the center wavelength of which is sensitive to the change in the environmental refractive index of the fiber end facet. Theoretical analysis not only shows excellent agreement with the experimental results, but also gives insights into the mechanisms of this kind of sensor. Using the center position of the Rayleigh peak as the response signal, a high sensitivity dλ/dn of 900 nm per unity refractive index is realized for this sensor and a resolution of Δn/n ≈ 1% is demonstrated in preliminary experiments. The sensitivity is solely determined by the period of the grating.
Well‐Defined Nanoclusters as Fluorescent Nanosensors: A Case Study on Au25(SG)18
Authors: Wu Zhikun , Wang Man , Yang Jiao , Zheng Xiaohong , Cai Weiping , Meng Guowen , Qian Huifeng , Wang Huimin , Jin Rongchao
Published: April 2012

The fluorescence of nanoparticles has attracted much attention in recent research, but in many cases the underlying mechanisms are difficult to evaluate due to the polydispersity of nanoparticles and their unknown structures, in particular the surface structures. Recent breakthroughs in the syntheses and structure determinations of well‐defined gold nanoclusters provide opportunities to conduct in‐depth investigations. Devising well‐defined nanocluster sensors based on fluorescence change is of particular interest not only for scientific studies but also for practical applications. Herein, the potential of the glutathionate (SG)‐capped Au25 nanocluster as a silver ion sensor is evaluated. The Ag+ detection limit of approximately 200 nM, based on the fluorescence enhancement and good linear fluorescence response in the silver ion concentration range from 20 nM to 11 μM, in combination with the good selectivity among 20 types of metal cations, makes Au25(SG)18 a good candidate for fluorescent sensors for silver ions. Further experiments reveal three important factors responsible for the unique fluorescence enhancement caused by silver ions: 1) the oxidation state change of Au25(SG)18; 2) the interaction of neutral silver species (Ag0, reduced by Au25(SG)18−) with Au25(SG)18; and 3) the interaction of Ag+ with Au25(SG)18. Experiments demonstrate the very different chemistry of hydrophobic Au25(SC2H4Ph)18 and hydrophilic Au25(SG)18 in the reaction with silver ions. This work indicates another potential application of gold nanoclusters, offers new strategies for nanocluster‐based chemical sensing, and reveals a new way to influence nanocluster chemistry for potential applications.
Physicochemical, morphological, structural, and thermal characteristics of starches separated from Bulbus fritillaria of different cultivars
Authors: Li Xia , Gao Wenyuan , Jiang Qianqian , Hao Juan , Guo Xinhua , Huang Luqi
Published: April 2012

The starches studied from the nine Fritillaria species had differently shaped and sized granules but all of them showed the presence of smooth, round, or elliptic‐shaped, indicating that the isolation process did not destroyed the starch granules. The nine Fritillaria starches presented different AM content, moisture content, ash content, particle size, swelling power, solubility, water absorption capacity and light transmittance. The starches isolated from Chuan‐Beimu species exhibited a higher amount of crude protein content and lower amount of AM than other the groups, which had lower swelling power, higher solubility and light transmittance. All the nine Fritillaria starches had an XRD pattern of the B‐type. In addition, F. hupehensis, F. walujewii and F. ussuriensis starches with fairly large‐sized or irregular granules had higher Tp and ΔHgel values than that isolated from the four Chuan‐Beimu species. The results obtained yielded information about the possible behavior of these starches when being used in certain applications. Cluster analysis results showed that this classification method based on macromolecule chemical compounds (starch) is original and credible in the quality control of various Beimu. In addition, it provided more information to the authentication systematics taxonomy methods including morphological, histological and molecular biological techniques of Fritillaria species.
Dendritic spine density in multisensory versus primary sensory cortex
Authors: Clemo H. Ruth , Meredith M. Alex
Published: April 2012

In sensory areas, neuronal dendritic spines receive sensory‐specific inputs whose net activity drives neuronal spiking responses to effective external stimuli. Previous studies indicate that neurons in primary sensory cortical areas, which largely receive inputs from a single sensory modality, exhibit an average of 0.5–1.4 dendritic spines/μm, depending on species. In higher‐order, associational cortices, inputs converge from multiple sensory sources onto individual, multisensory neurons. This raises the question: when inputs from two different modalities converge onto individual neurons, how are the dendritic spines apportioned to subserve the generation of robust spiking responses to each modality? As inputs arrive from two different sensory sources, it might be expected that neurons in multisensory areas exhibit approximately double the spine density of neurons in areas that receive just one sensory input. The present study examined this possibility in Golgi‐stained neurons from ferret primary auditory (A1) and somatosensory (S1) cortices, as well as from regions in which inputs from two different sensory modalities converge: the lateral rostral suprasylvian sulcus (LRSS) and the rostral posterior parietal (PPr) areas. Dendritic spine density (spines/μm) was measured for pyramidal neurons in layers 2–3 and layers 5–6 for each cortical area from three animals using light microscopy. Primary sensory regions A1 and S1 showed remarkably similar average spine densities (A1 = 1.27 spines/μm ± 0.3 s.d.; S1 = 1.14 spines/μm ± 0.3), but average spine densities from the multisensory areas were lower (LRSS = 0.98 ± 0.3; PPr = 1.04 ± 0.3). Thus, for a given cortical area, dendritic spine density appears to be determined by factors other than the levels of sensory modality convergence. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
Extensive Ace2 duplication and multiple mutations on Ace1 and Ace2 are related with high level of organophosphates resistance in Aphis gossypii
Authors: Shang Qingli , Pan Yiou , Fang Kui , Xi Jinghui , Wong Andrew , Brennan James Andrew , Cao Chuanwang
Published: April 2012

Aphis gossypii (Glover) has been found to possess multiple mutations in the acetylcholinesterase (AChE) gene (Ace) that might involve target site insensitivity. In vitro functional expression of AChEs reveals that the resistant Ace1 (Ace1R) and Ace2 (Ace2R) were significantly less inhibited by eserine, omethoate, and malaoxon than the susceptible Ace1 (Ace1S) and Ace2 (Ace2S). Furthermore, in both the mutant and susceptible AChEs, Ace2 was significantly less sensitive to eserine, omethoate, and malaoxon than Ace1. These results suggested that both the mutant Ace1 and Ace2 were responsible for omethoate resistance, while the mutant Ace2 played a major role in insecticide resistance. The DNA copy number and transcription level of Ace2 were 1.52‐ and 1.88‐fold higher in the ORR strain than in the OSS strain. Furthermore, the DNA copy number and transcription level of Ace2 were significantly higher than that of Ace1 in either OSS or ORR strains, demonstrating the involvement of Ace2 gene duplication in resistance. Thus, the authors conclude that omethoate resistance in cotton aphids appears to have evolved through a combination of multiple mutations and extensive Ace2R gene duplication. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 526–533, 2014.
Using Digital Texts to Promote Fluent Reading
Authors: Thoermer Andrea , Williams Lunetta
Published: April 2012

Fluency is a critical skill of adept readers. As listening to read alouds and performing Readers Theatre scripts are two prevalent strategies that can increase students' fluency skills, this article provides suggestions in using these strategies with digital texts through free, online resources. Digital texts can be accessed using a desktop, laptop, or handheld computer such as the iPad and can serve as a unique medium to motivate students to want to read and practice fluency skills and strategies. A table is included for teachers to explore other Web sites that can enhance students' fluency through digital texts.
A conception on the terahertz communication system for plasma sheath penetration
Authors: Li Jin , Pi Yiming , Yang Xiaobo
Published: April 2012

The signal of a hypersonic spacecraft entering the Earth's atmosphere may be lost at a certain altitude transitorily. This phenomenon is called “blackout,” an important performance feature of aircraft design. Recently, with the development of the nearcraft, communication techniques under the plasma environment have increasingly become more important, with the realization that we can record, monitor, track, and capture the nearcraft. In this paper, an idea based on the capability of radiation from the terahertz communication system to penetrate the plasma sheath is proposed to provide the theoretical basis for real‐time communication with the nearcraft. Copyright © 2012 John Wiley & Sons, Ltd.
Long‐term efficacy of miglustat in paediatric patients with Niemann‐Pick disease type C
Authors: Chien Y. H. , Peng S. F. , Yang C. C. , Lee N. C. , Tsai L. K. , Huang A. C. , Su S. C. , Tseng C. C. , Hwu W. L.
Published: April 2012

Niemann‐Pick disease type C (NP‐C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP‐C in Europe in 2009. There are still relatively few published data on the long‐term efficacy and safety of miglustat in patients with NP‐C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1–3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration‐penetration index scores among four evaluable patients (p > 0.05). Scores on the mini‐mental state examination indicated an improvement in cognitive function during the first 3–6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.
The emerging contribution of sequence context to the specificity of protein interactions mediated by PDZ domains
Authors: Luck Katja , Charbonnier Sebastian , Travé Gilles
Published: April 2012

The canonical binding mode of PDZ domains to target motifs involves a small interface, unlikely to fully account for PDZ‐target interaction specificities. Here, we review recent work on sequence context, defined as the regions surrounding not only the PDZ domains but also their target motifs. We also address the theoretical problem of defining the core of PDZ domains and the practical issue of designing PDZ constructs. Sequence context is found to introduce structural diversity, to impact the stability and solubility of constructs, and to deeply influence binding affinity and specificity, thereby increasing the difficulty of predicting PDZ‐motif interactions. We expect that sequence context will have similar importance for other protein interactions mediated by globular domains binding to short linear motifs.