bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer
Authors: Zhang Lu , Komurov Kakajan , Wright Woodring E. , Shay Jerry W.
Published: June 2012

Cancer genome sequencing efforts are leading to the identification of genetic mutations in many types of malignancy. However, the majority of these genetic alterations have been considered random passengers that do not directly contribute to tumorigenesis. We have previously conducted a soft agar‐based short hairpin RNA (shRNA) screen within colorectal cancer (CRC) candidate driver genes (CAN‐genes) using a karyotypically diploid hTERT‐ and CDK4‐immortalized human colonic epithelial cell (HCEC) model and discovered that depletion of 65 of the 151 CAN‐genes enhanced anchorage‐independent growth in HCECs with ectopic expression of K‐RasV12 and/or TP53 knockdown. We now constructed an interaction map of the confirmed CAN‐genes with CRC non‐CAN‐genes and screened for functional tumor suppressors. Remarkably, depletion of 15 out of 25 presumed passenger genes that interact with confirmed CAN‐genes (60%) promoted soft agar growth in HCECs with TP53 knockdown compared to only 7 out of 55 (12.5%) of presumed passenger genes that do not interact. We have thus demonstrated a pool of driver mutations among the putative CRC passenger/incidental mutations, establishing the importance of employing biological filters, in addition to bioinformatics, to identify driver mutations.
Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2‐like polarization of tumor associated macrophages
Authors: Pickert Geethanjali , Lim Hee‐Young , Weigert Andreas , Häussler Annett , Myrczek Thekla , Waldner Maximilian , Labocha Sandra , Ferreirós Nerea , Geisslinger Gerd , Lötsch Jörn , Becker Christoph , Brüne Bernhard , Tegeder Irmgard
Published: June 2012

GTP cyclohydrolase (GCH1) is the key‐enzyme to produce the essential enzyme cofactor, tetrahydrobiopterin. The byproduct, neopterin is increased in advanced human cancer and used as cancer‐biomarker, suggesting that pathologically increased GCH1 activity may promote tumor growth. We found that inhibition or silencing of GCH1 reduced tumor cell proliferation and survival and the tube formation of human umbilical vein endothelial cells, which upon hypoxia increased GCH1 and endothelial NOS expression, the latter prevented by inhibition of GCH1. In nude mice xenografted with HT29‐Luc colon cancer cells GCH1 inhibition reduced tumor growth and angiogenesis, determined by in vivo luciferase and near‐infrared imaging of newly formed blood vessels. The treatment with the GCH1 inhibitor shifted the phenotype of tumor associated macrophages from the proangiogenic M2 towards M1, accompanied with a shift of plasma chemokine profiles towards tumor‐attacking chemokines including CXCL10 and RANTES. GCH1 expression was increased in mouse AOM/DSS‐induced colon tumors and in high grade human colon and skin cancer and oppositely, the growth of GCH1‐deficient HT29‐Luc tumor cells in mice was strongly reduced. The data suggest that GCH1 inhibition reduces tumor growth by (i) direct killing of tumor cells, (ii) by inhibiting angiogenesis, and (iii) by enhancing the antitumoral immune response.
Polyaniline Doped with Various Inorganic Acids and Polymeric Acids as Platinum Catalyst Support for Methanol Electro‐oxidation
Authors: Kuo Chung‐Wen , Kuo Ping‐Lin , Ho Ko‐Shan , Hsieh Tar‐Hwa , Chen Sin‐Jhih , Wu Tzi‐Yi , Huang Yu‐Chang
Published: July 2012

Polyaniline (PANI) is doped with H2SO4, HCl, poly(acrylic acid) (PAA), poly(acrylic acid‐co‐maleic acid) (PAMA), PAA+HCl, and poly(styrenesulfonic acid) (PSS) to obtain PANI‐H2SO4, PANI‐HCl, PANI‐PAA, PANI‐PAMA, PANI‐(PAA+HCl), and PANI‐PSS films, respectively. Ultraviolet‐visible (UV‐Vis) and Fourier transform infrared (FT‐IR) spectroscopy result confirm that PANI is doped with PSS. X‐ray photoelectron spectroscopy (XPS) results indicate that the nitrogen atoms of PANI‐PSS are the most positively charged in these films. Scanning electron microscopy (SEM) images reveal that these films are composed of highly porous nanowires. Platinum (Pt) can be incorporated into PANI‐H2SO4, PANI‐HCl, PANI‐PAA, PANI‐PAMA, PANI‐(PAA+HCl), and PANI‐PSS films via electrochemical deposition to obtain PANI‐H2SO4‐Pt, PANI‐HCl‐Pt, PANI‐PAA‐Pt, PANI‐PAMA‐Pt, PANI‐(PAA+HCl)‐Pt, and PANI‐PSS‐Pt composite electrodes, respectively. Auger electron spectroscopy (AES) results indicate that Pt particles disperse more uniformly into the spatial regions of PANI‐PSS and PANI‐(PAA+HCl) than those of other films. The PANI‐PSS‐Pt electrode provides the most active surface area of Pt in these electrodes. Cyclic voltammetry results and chronoamperometric response measurements show that the activity and stability toward methanol oxidation of the PANI‐PSS‐Pt electrode are the best in these electrodes.
The Astrochemical Observatory: Molecules in the Laboratory and in the Cosmos
Authors: Palazzetti Federico , Maciel Glauciete S. , Lombardi Andrea , Grossi Gaia , Aquilanti Vincenzo
Published: July 2012

Astrochemistry is a discipline consolidated recently, although its roots extend back to the dawn of early civilization with the observation and mapping of the sky. The way to the understanding of the common natural laws on earth and in space paved by Galilei's observations by the telescope, has been extended in the last decades, by new technologies such as radioastronomy and space missions. Plenty of new chemistry was surprisingly discovered. Extreme rich information on the chemical “composition” of the universe is being obtained, either from the other planets and satellites in the Solar System, from meteorites and comets, or from the interstellar space. In this article we will present selected topics regarding the chemical structures and reactions being discovered. Particular attention will be devoted to aspects considered as relevant for the prebiotic processes on earth, such as those involving chirality and its role played in the origin and evolution of life.
Accumulation of Miscanthus‐derived carbon in soils in relation to soil depth and duration of land use under commercial farming conditions
Authors: Felten Daniel , Emmerling Christoph
Published: July 2012

Bioenergy is becoming an important option in Global Change mitigation policy world‐wide. In agriculture, cultivation of energy crops for biodiesel, biogas, or bioethanol production received considerable attention in the past decades. Beyond this, the cultivation of Miscanthus, used as solid fuel for combustion, may lead to an increase in soil organic matter content compared to other agricultural land use, since C‐sequestration potential in soils of Miscanthus crops is high due to, e.g., high amounts of harvest residues. This may indirectly contribute to a reduction of atmospheric CO2 concentration. The objective of the present work was to investigate the development of soil organic carbon and Miscanthus‐derived C contents, as well as to estimate carbon stocks in soils cultivated with Miscanthus using 13C‐natural‐abundance technique. The investigations were carried out in relation to soil depth up to 150 cm in a sequence of 2, 5, and 16 y of cultivation relative to a reference soil cultivated with cereals. Amounts of total organic C (TOC) and Miscanthus‐derived C (Miscanthus‐C) increased with increasing duration of cultivation. For example, TOC increased from 12.8 to 21.3 g C kg–1 after 16 y of cultivation at the depth of 0–15 cm, whereby the portion of Miscanthus‐C reached 5.8 g C kg–1. Also within deeper soil layers down to 60 cm depth a significant enhancement of Miscanthus‐C was detectable even though TOC contents were not significantly enhanced. At soil depth below 60 cm, no significant differences between treatments were found for Miscanthus‐C. Within 16 y of continuous commercial farming, Miscanthus stands accumulated a total of 17.7 Mg C ha–1 derived from Miscanthus residues (C4‐C), which is equivalent to 1.1 Mg C4‐C ha–1 y–1. The annual surplus might function as CO2 credit within a greenhouse‐gas balance. Moreover, the beneficial properties of Miscanthus cultivation combined with a low requirement on fertilization may justify the status of Miscanthus as a sustainable low‐input bioenergy crop.
Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram‐negative and gram‐positive bacteria
Authors: Huang Liyi , Xuan Yi , Koide Yuichiro , Zhiyentayev Timur , Tanaka Masamitsu , Hamblin Michael R.
Published: July 2012

Background and Objectives

Antimicrobial photodynamic therapy (APDT) employs a non‐toxic photosensitizer (PS) and visible light, which in the presence of oxygen produce reactive oxygen species (ROS), such as singlet oxygen (1O2, produced via Type II mechanism) and hydroxyl radical (HO., produced via Type I mechanism). This study examined the relative contributions of 1O2 and HO. to APDT killing of Gram‐positive and Gram‐negative bacteria.

Study Design/Materials and Methods

Fluorescence probes, 3′‐(p‐hydroxyphenyl)‐fluorescein (HPF) and singlet oxygen sensor green reagent (SOSG) were used to determine HO. and 1O2 produced by illumination of two PS: tris‐cationic‐buckminsterfullerene (BB6) and a conjugate between polyethylenimine and chlorin(e6) (PEI–ce6). Dimethylthiourea is a HO. scavenger, while sodium azide (NaN3) is a quencher of 1O2. Both APDT and killing by Fenton reaction (chemical generation of HO.) were carried out on Gram‐positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram‐negative bacteria (Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa).

Results

Conjugate PEI‐ce6 mainly produced 1O2 (quenched by NaN3), while BB6 produced HO. in addition to 1O2 when NaN3 potentiated probe activation. NaN3 also potentiated HPF activation by Fenton reagent. All bacteria were killed by Fenton reagent but Gram‐positive bacteria needed a higher concentration than Gram‐negatives. NaN3 potentiated Fenton‐mediated killing of all bacteria. The ratio of APDT killing between Gram‐positive and Gram‐negative bacteria was 2 or 4:1 for BB6 and 25:1 for conjugate PEI‐ce6. There was a NaN3 dose‐dependent inhibition of APDT killing using both PEI‐ce6 and BB6 against Gram‐negative bacteria while NaN3 almost failed to inhibit killing of Gram‐positive bacteria.

Conclusion

Azidyl radicals may be formed from NaN3 and HO.. It may be that Gram‐negative bacteria are more susceptible to HO. while Gram‐positive bacteria are more susceptible to 1O2. The differences in NaN3 inhibition may reflect differences in the extent of PS binding to bacteria (microenvironment) or differences in penetration of NaN3 into cell walls of bacteria. Lasers Surg. Med. 44: 490–499, 2012. © Wiley Periodicals, Inc.
Isothianaphthene‐Based Conjugated Polymers for Organic Photovoltaic Cells
Authors: Long Guankui , Wan Xiangjian , Zhou Jiaoyan , Liu Yongsheng , Li Zhi , He Guangrui , Zhang Mingtao , Hou Yanhui , Chen Yongsheng
Published: July 2012

Two novel copolymers PBDT‐DEAITN and PBDT‐DOAITN containing the same backbone of isothianaphthene (ITN) quinoidal and benzodithiophene (BDT) donor units are synthesized and their organic photovoltaic (OPV) devices are fabricated. Although these two polymers have rather low optical bandgaps, 1.52 and 1.58 eV for PBDT‐DEAITN and PBDT‐DOAITN, respectively, their OPV cells exhibit rather limited power conversion efficiencies of 1.25% and 1.20% under an AM1.5G simulated solar light. The reasons for the low OPV performance are investigated by structure modeling calculation. Based on this and the screening results for the representative quinoidal polymers in the literatures, a strategy of designing high‐ performance planar polymers based on ITN unit is proposed.
Fractional Crystallization and Phase Segregation in Binary Miscible Poly(butylene succinate)/Poly(ethylene oxide) Crystalline Blends: Effect of Crystallization Temperature
Authors: Pan Pengju , Zhao Li , Yang Jinjun , Inoue Yoshio
Published: July 2012

The effects of crystallization temperature of PBS (TIC,PBS) on the fractional crystallization, phase segregation, and crystalline morphology of PEO in their miscible crystalline/crystalline blends are investigated. The crystallization kinetics and phase segregation of PEO are considerably influenced by TIC,PBS. A higher TIC,PBS results in the crystallization of PEO at an extremely large degree of supercooling and may facilitate the segregation of PEO within the interlamellar regions of PBS. At a high TIC,PBS (e.g., 95 °C), the long period, thickness of amorphous and crystalline layers of PBS increase upon blending with PEO. The TIC,PBS dependence of phase segregation of the PEO component is discussed from a thermodynamic as well as a kinetic perspective.

magnified image
Living Polymerization of N‐Substituted β‐Alanine N‐Carboxyanhydrides: Kinetic Investigations and Preparation of an Amphiphilic Block Copoly‐β‐Peptoid
Authors: Grossmann Arlett , Luxenhofer Robert
Published: July 2012

Poly(α‐peptoid)s (N‐substituted polyglycines) are interesting peptidomimetic biomaterials that have been discussed for many applications. Poly(β‐peptoid)s (N‐substituted poly‐β‐alanines), although equally intriguing, have received much less attention. Here we present results that suggest that while N‐substituted β‐alanine N‐carboxyanhydrides can undergo a living nucleophilic ring‐opening polymerization, the solubility of poly(β‐peptoid)s can be very poor, which contributes to the limited accessibility using other synthetic approaches. The living character of the polymerization was utilized for the preparation of the first polymerized amphiphilic block copoly‐β‐peptoid. Our results may open a new route towards highly defined functional poly(β‐peptoid)s which could represent biomaterials.
Stereochemical behavior of 2 J(Se,H) and 3 J(Se,H) spin‐spin coupling constants across sp3 carbons: a theoretical scrutiny
Authors: Rusakov Yury Yu. , Krivdin Leonid B.
Published: July 2012

A theoretical study of geminal and vicinal 77Se‐1 H coupling constants in the benchmark dimethyl and diethyl selenides has been performed at the SOPPA level followed by the NJC analysis within the NBO approach to reveal their stereochemical behavior in respect with the three main structural factors, namely, (i) the dihedral angle dependences, (ii) the bond angle dependences and (iii) the lone pair effects. It has been demonstrated that both geminal and vicinal couplings provide a unique stereospecificity in respect with the orientational lone pair effect together with the geometry of a coupling pathway, which is of prime importance for the stereochemical studies of organoselenium compounds. Copyright © 2012 John Wiley & Sons, Ltd.
Reduced blood flow artifact in intraplaque hemorrhage imaging using CineMPRAGE
Authors: Mendes Jason , Parker Dennis L. , Kim Seong‐Eun , Treiman Gerald S.
Published: July 2012

Magnetization prepared rapid acquisition gradient echo (3D MPRAGE) has been shown to be a sensitive method to image carotid intraplaque hemorrhage. As the MPRAGE sequence used to identify potential intraplaque hemorrhage does not utilize cardiac gating, it is difficult to optimize the inversion times due to the dynamic nature of flowing blood. As a result, a best fit inversion time is often determined experimentally and then used for in vivo clinical examination. This results in compromised blood suppression and occasional hemorrhage mimicking flow artifacts. We demonstrate that a retrospective cardiac correlated reconstruction can be applied to the conventional MPRAGE sequence (CineMPRAGE) to more accurately identify blood signal. This CineMPRAGE reconstruction uses the data from a standard nongated MPRAGE sequence to generate a full sequence of cardiac correlated images throughout the cardiac cycle and, therefore, provides a dynamic view of the carotid artery and a better ability to discern blood signal from potential intraplaque hemorrhage. In our preliminary study of 35 patients, signal from potential hemorrhage was constant over the cardiac cycle, whereas any signal from blood flow artifact was observed as an oscillating signal over the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Multidirectional high‐moment encoding in phase contrast MRI
Authors: Zwart Nicholas R. , Pipe James G.
Published: July 2012

The use of phase contrast MRI to measure vascular flow provides a unique method for acquiring quantitative estimates of flow as well as morphological imaging. The quantitative aspects of phase contrast magnetic resonance angiography (PC‐MRA) provide unique relationships between measurement parameters and resulting signal to noise ratio of the velocity measurements. This article introduces a new method to exploit these relationships providing increased efficiency, and therefore, higher vessel conspicuity. Signal to noise ratio gains in high‐moment PC‐MRA are limited by the ability to unalias phase measurements that fall outside the −π to π interval. Unaliasing phase on a per pixel basis is limited by errors in the measurements due to noise and intravoxel flow distributions. Current dual‐VENC methods have been shown to be robust to these errors and provide high velocity to noise ratio gains, however, the collection of a required high‐VENC set can be inefficient. The presented method provides more time efficient gains in velocity to noise ratio compared to a dual‐VENC approach by eliminating the high‐VENC acquisitions and using shared information between nonorthogonal measurements. Simulations, phantom, and in vivo angiography are used to characterize the noise performance of each method. The velocity to noise ratio efficiency of the proposed method is shown to be ∼1.7 times greater than the dual‐VENC method at the same gradient moment. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Understanding the interactions in acrylic copolymer/1‐butyl‐3‐methylimidazolium chloride from solution rheology
Authors: Zhu Xinjun , Chen Xun , Wang Xiao , Saba Hina , Zhang Yumei , Wang Huaping
Published: July 2012

The effects of the type and content of comonomers on the rheological properties of acrylic copolymers in 1‐butyl‐3‐methylimidazolium chloride ([BMIM]Cl) were explored. According to the de Gennes scaling law for solution, comparison of intrinsic viscosity and scaling analysis of the exponent in the specific viscosity‐ and relaxation time‐concentration power law indicated that solution of both polyacrylonitrile (PAN) homo‐polymer and copolymer poly(acrylonitrile‐co‐methyl acrylate) (poly(AN‐co‐MA)) in [BMIM]Cl behave in the same manner as neutral polymer in a θ‐solvent. However, [BMIM]Cl acts as a more good solvent for poly(acrylonitrile‐co‐acrylamide) (poly(AN‐co‐AM)). The dissolution and unique rheological behavior of such solutions have been attributed to the interactions between copolymer chains and [BMIM]Cl. The interactions between nitrile group (−C≡N) and 1‐butyl‐3‐methylimidazolium cation ([BMIM]+) should interrupt and break the dipolar‐dipolar interactions of PAN resulting in the subsequent dissolution of the polymer in [BMIM]Cl. Such interactions between −C≡N and [BMIM]+ion are still dominated by the solvating ability of poly(AN‐co‐MA) in [BMIM]Cl, even though carbonyl group (C=O) in MA repeating unit could coordinate to cation of the ionic liquid. The salvation capacity of [BMIM]Cl for poly(AN‐co‐AM) can be evidently improved due to the extra hydrogen bond interactions between −NH2group of AM and anion of [BMIM]Cl. Copyright © 2012 John Wiley & Sons, Ltd.
The synthesis of covalent bonded single‐walled carbon nanotube/polyvinylimidazole composites by in situ polymerization and their physical characterization
Authors: Tekin Nalan , Beyaz Saadet Kayiran , Kara Ali , Şimşek Eyüp , Lamari Farida Darkrim , Çakmak Gülbeden , Güney Hasan Yüksel
Published: July 2012

Single‐walled carbon nanotube (SWCNT) polyvinylimidazole (PVI) composites have been prepared by in situ emulsion polymerization. Dispersion of raw SWCNTs in the PVI matrix was improved by surface modification of the SWCNTs using nitric acid treatment and air oxidation. The carbonyl‐terminated SWCNTs were covalently bonded to PVI by in situ polymerization and the SWCNT/PVI composite was thus obtained. The morphological and structural characterizations of the surface‐functionalized SWCNTs and SWCNT/PVI composites were carried out by Fourier transform infrared spectroscopy, X‐ray diffraction, conductivity measurements, scanning, and transmission electron microscopy. Thermograms of the materials were determined by the differential scanning calorimetry technique. The characterization results indicate that PVI was covalently bonded to SWCNTs and a new material was then obtained. The functionalized SWCNTs showed homogenous dispersion in the composites, whereas purified SWCNT resulted in poor dispersion and nanotube agglomeration. SWCNT/PVI composites exhibited chemical stability enhancement in many common solvents. I–V curves of the samples exhibit an ohmic character. Conductivity values for pure SWCNTs, pure PVI and SWCNT/PVI composite were measured to be 3.47, 2.11 × 10−9, and 2.3 × 10−3 S/m, respectively. Because of resonance, a large dielectric constant is obtained for SWCNT/PVI composite, which is not observed for ordinary materials. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Film formation from PS/AL2O3 nanocomposites prepared by dip‐drawing method
Authors: Uğur Şaziye , Kışlak Yusuf
Published: July 2012

In this study, steady state fluorescence (SSF) and UV–vis (UVV) techniques were used to examine film formation from pyrene (P) labeled polystyrene (PS) latex/Al2O3 (PS/Al2O3) composites prepared by the dip‐drawing method. The effects of dip‐drawing rates and dipping time in Al2O3 sol on film formation behavior and the morphology of PS/Al2O3 films were investigated. Films were prepared first by casting PS dispersion on clean glass substrates which creates a close‐packed array of PS sphere (203 nm) templates. These templates were then covered with Al2O3 utilizing the dip‐drawing method for various dip‐drawing rates and dipping times in Al2O3 sol. The film formation of these composites was studied by annealing them at a temperature range of 100°C to 270°C and monitoring the scattered light (Isc), fluorescence (IP), and transmitted light (Itr) intensities after each annealing step. The structural properties of the composite films were analyzed with a scanning electron microscope (SEM). The results demonstrated that the film formation behavior and morphology of composites depended mainly on dipping time, and no dependence on the dip‐drawing rate was observed. The optical results indicated that PS/Al2O3 films undergo complete film formation independent of the dip‐drawing rate and dipping time. Additionally, the film formation stages were modeled and the corresponding activation energies were determined. After completion of film formation, PS polymers were extracted to obtain porous Al2O3 thin films. Highly ordered porous structures were observed for long dipping time in Al2O3 sol but no change was observed for different dip‐drawing rates, confirming the optical data. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Electrical conductivity of polyurethane/MWCNT nanocomposite foams
Authors: Athanasopoulos N. , Baltopoulos A. , Matzakou M. , Vavouliotis A. , Kostopoulos V.
Published: July 2012

Polymeric foams with electrical conductivity represent a novel and very interesting class of materials rather sporadically studied. In this study, the feasibility to prepare electrically conductive Rigid Polyurethane (PUR) foams at various densities using multiwall carbon nanotubes (MWCNT) at varying contents was investigated. The produced PUR/MWCNT foams exhibited electrical conductivity over a wide range of densities and nanofiller contents. The effect of these two parameters on the electrical conductivity of the final foam system was studied. To explain the behavior, Statistical Percolation laws were employed. Model parameters were elaborated for both cases showing that the percolation model can adequately describe the behavior. The foaming process is analyzed in further detail to assist in the explanation and understanding of theexperimental observations. Finally, a material design map is proposed for the preparation of electrically conductive foams. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Analysis of synergistic effect of nanozinc/nanoclay additives on the corrosion performance of zinc‐rich polyurethane nanocomposite coatings
Authors: Arianpouya N. , Shishesaz M. , Ashrafi A.
Published: July 2012

The aim of this study was to analyze the synergistic effect of clay and zinc nanopigments. Therefore different percentages of Montmorillonite clay nanolayers were added to zinc‐rich polyurethane nanocomposites. Ultrasonication process was used to prepare polyurethane/nanozinc/nanoclay nanocomposites. Then coatings were applied on steel panels with composition of 10 wt% nanozinc and 0.5, 1, 1.5, and 2 wt% nanoclay. TEM and XRD were used to analyze the structural characteristics of the nanocomposites. The results of the structure analysis revealed the size of nanomaterials and confirmed the appropriate dispersion in polymer matrix. The anticorrosive properties of the nanocomposites were investigated using salt fog test and electrochemical impedance spectroscopy (EIS). The results of EIS showed that addition of clay nanolayers improves the corrosion resistance of coatings and the best corrosion performance obtained for the nanocomposite sample with 2 wt% nanoclay. Also, according to the results of the salt spray test, the sample with 2 wt% nanoclay showed the least H2O penetration and exfoliation adjacent to the scratches. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light–heavy interchain disulfide bond architecture
Authors: Heads James T. , Adams Ralph , D'Hooghe Lena E. , Page Matt J. T. , Humphreys David P. , Popplewell Andrew G. , Lawson Alastair D. , Henry Alistair J.
Published: July 2012

The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 CH1 and IgG4 CH1 domains, while retaining the native IgG1 light‐heavy interchain disulfide (L–H) bond, did not affect thermal stability. Introducing the IgG1 type L–H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L–H interchain DSB with the IgG4 type L–H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format.
The crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA
Authors: Kwon Eunju , Kim Dong Young , Ngo Tri Duc , Gross Carol A. , Gross John D. , Kim Kyeong Kyu
Published: July 2012

The Cpx two‐component system of Gram‐negative bacteria senses extracytoplasmic stresses using the histidine kinase CpxA, a membrane‐bound sensor, and controls the transcription of the genes involved in stress response by the cytosolic response regulator CpxR, which is activated by the phosphorelay from CpxA. CpxP, a CpxA‐associated protein, also plays an important role in the regulation of the Cpx system by inhibiting the autophosphorylation of CpxA. Although the stress signals and physiological roles of the Cpx system have been extensively studied, the lack of structural information has limited the understanding of the detailed mechanism of ligand binding and regulation of CpxA. In this study, we solved the crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA (VpCpxA‐peri) to a resolution of 2.1 Å and investigated its interaction with CpxP. VpCpxA‐peri has a globular Per‐ARNT‐SIM (PAS) domain and a protruded C‐terminal tail, which may be required for ligand sensing and CpxP binding, respectively. The direct interaction of the PAS core of VpCpxA‐peri with VpCpxP was not detected by NMR, suggesting that the C‐terminal tail or other factors, such as the membrane environment, are necessary for the binding of CpxA to CpxP.
Cloning, characterisation and expression profiling of the cDNA encoding the ryanodine receptor in diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae)
Authors: Guo Lei , Tang Baozhen , Dong Wei , Liang Pei , Gao Xiwu
Published: July 2012

BACKGROUND: The rynodine receptors (RyRs) are the main targets of diamide insecticides such as chlorantraniliprole. To provide the basis for a good understanding of the molecular mechanisms of diamide insecticide resistance, an RyR gene from Plutella xylostella was cloned and characterised in the present paper.

RESULTS: A full‐length cDNA sequence of RyR was cloned from P. xylostella through RT‐PCR and rapid amplification of cDNA ends (RACE). The gene (named PxRyR1) is 15 753 bp long, with an open reading frame of 15 354 bp, encoding a predicted RyR of 5117 amino acids. An alternative splicing of the PxRyR1 was also cloned and named PxRyR2. The PxRyR1 shares 77–93% identity with other insect RyRs. Quantitative real‐time PCR analysis showed that the PxRyR was expressed at a high level in second‐instar larvae and adults, at a low level in prepupae and pupae and abundantly in the body wall muscle and head (respectively 6.00 and 3.12 times the expression in the gut). Western blot analysis with anti‐RyR antibodies showed that the RyR was mainly present in the body wall muscle and head, but barely present in the haemocyte and gut.

CONCLUSIONS: There are at least two alternative splices of PxRyR expressed in all developmental stages and tissues in P. xylostella at various levels. The results provided the basis for further understanding of the mechanisms of resistance to diamide insecticides in P. xylostella. Copyright © 2012 Society of Chemical Industry
Stability, toxicity and biological activity of retro, inversed and retro‐inversed glucagon isomers
Authors: Krasniqi Besnik , Scruten Erin , Piller Jaret , Lee Jeremy , Napper Scott
Published: July 2012

Peptide modifications that improve pharmacological properties are of considerable therapeutic importance. Here we consider the retro (R), inversed (D) and retro‐inversed (RI) isomers of glucagon with respect to structure, stability, toxicity and biological activity. Biologically, RI‐glucagon demonstrated comparable in vivo activity as L‐glucagon with respect to magnitude and duration of blood sugar elevation following i.p. administration to mice. Structurally, the isomers were investigated through circular dichroism (CD) and nanopore analysis. CD demonstrated a conserved potential for formation of secondary structure, which was independent of the direction of the peptide (L vs R; D vs RI) as well as formation of symmetry‐related structures for the chiral isomers (L vs D; R vs RI). CD, therefore, discriminated chiral but not directional isomers. Nanopore analysis, which depends on interaction of the peptides with chiral pores, discriminated all four isomers on the basis of unique signatures of bumping and translocation. Nanopore analysis offered greater opportunity than CD to discriminate the isomers although neither technique provided a definitive biomarker of biological activity. Functionally, the R and RI isomers resist proteolytic degradation and none of the isomers possess hemolytic activity or cellular toxicity. Collectively, this investigation highlights the potentials and limitations of CD and nanopore analysis for investigation of peptide isomers as well as offering insight into the structural criteria to mimic peptide biological activity. For this example, retro‐inversion, through undefined contributions of increased stability and maintained biological activity, was best suited to mimic the biological activity of the parent peptide. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
High gravity‐wave activity observed in Patagonia, Southern America: generation by a cyclone passage over the Andes mountain range
Authors: Pulido M. , Rodas C. , Dechat D. , Lucini M. M.
Published: July 2012

The Antarctic peninsula and Patagonia region (the south of South America) have recently been identified as the regions with the highest gravity‐wave activity in the world. In this work, the generation and propagation of gravity waves in the Patagonia region in an event of strong wave activity from 30 October 1995–1 November 1995 is examined by means of radiosonde measurements and simulations with the Weather Research and Forecasting (WRF) model. The waves are generated by strong surface winds found near the Andes mountains at a latitude of 49–51°S. The strong low‐level winds are related to an extratropical cyclone that propagates southeastward in the South Pacific ocean and approaches the western coast of the continent. The waves propagate southeast toward Tierra del Fuego and they continue their propagation over the Drake Passage. They are found to propagate long meridional (lateral) distances due to the shear background conditions. This fact is corroborated with WRF simulations and a novel technique that combines wavelet analysis and backward ray‐tracing. Therefore, this work provides further evidence that high gravity‐wave activity found by several studies over Drake Passage may have an orographic origin. During the orographic wave event, which lasts about 72 hours, the horizontal wavelength is unexpectedly found to change day‐to‐day. The analysis shows that changes in the near‐surface meteorological conditions produced by the cyclone passage may trigger different components of the forcing orography. The orographic waves propagate toward their critical levels, which are found at 25 km and above. The radiosonde measurements show that the wave is breaking continuously along a wide altitude range; this finding from measurements supports the picture of continuous wave erosion along the ray path instead of abrupt wave‐breaking for the examined wave event. Copyright © 2012 Royal Meteorological Society
Flow during the evening transition over steep Alpine slopes
Authors: Nadeau Daniel F. , Pardyjak Eric R. , Higgins Chad W. , Huwald Hendrik , Parlange Marc B.
Published: July 2012

A field campaign, the Slope Experiment near La Fouly (SELF‐2010), was conducted to monitor the evening transition of slope flows on clear‐sky days from July to September 2010 in a narrow valley of the Swiss Alps. A steep west‐facing slope with inclinations ranging from 25° to 45° was instrumented from 1900 m to 2200 m above sea‐level. Detailed measurements were made along a linear transect of the slope with two turbulence towers, two weather stations, five surface temperature measurement stations and a tethered balloon system. The present study focuses on nine exemplary ‘convective’ days, characterized by weak synoptic flow and clear‐sky conditions, during which thermal circulations prevail. The analysis of the observational data shows that topographic shading triggers the evening transition. The topographic configuration around the experimental site results in a sharply defined ‘shading front’ propagating upslope, causing a sudden decrease in incoming short‐wave radiation on the order of several hundreds of W m−2 within a few minutes. The slope surface rapidly responds to the advancing shading front; in some cases, reductions in surface temperatures of some 10°C in less than 10 min are observed. This is rapidly followed by an early‐evening calm period with very small turbulent kinetic energy (TKE< 0.05 m 2 s−2) and extremely light wind speeds (< 0.5 m s−1). When the inertia‐driven upslope flow is fully stopped by the katabatic acceleration, a shallow local drainage flow forms and reaches a quasi‐equilibrium 1.5 h after the local sunset. An analysis of the TKE budget close to the surface shows that the buoyancy flux is much greater than the shear production in the last hours before the local sunset, possibly due to valley curvature effects. Copyright © 2012 Royal Meteorological Society
Variation of compound‐specific hydrogen isotope ratios under changing temperature program in gas chromatography/thermal conversion/isotope ratio mass spectrometry
Authors: Liu Weiguo , Wang Zheng , Cui Linlin , Sauer Peter E. , Cao Yunning
Published: July 2012

RATIONALE

In recent experiments, we found that compound‐specific δ2H values can vary as a result of changing the gas chromatography temperature program under common pyrolysis conditions. To achieve better precision, it is necessary to examine the details and find a solution to this problem when using gas chromatography/thermal conversion/isotope ratio mass spectrometry (GC‐TC‐IRMS) for hydrogen isotope analysis.

METHODS

A test was designed to find the possible temperature effect under four different GC temperature ramp rates using n‐alkanes (n‐C21, n‐C27, and n‐C31) and fatty acids (n‐C12, n‐C18, and n‐C24). The common 'hexane' method was used initially to condition the pyrolysis reactor. Experiments were then carried out using the 'methane condition' method because it was considered to improve pyrolysis efficiency.

RESULTS

Under the 'hexane condition' the measured hydrogen isotope ratios of the n‐alkanes and n‐fatty acids became more positive with increasing GC temperature ramp rate. The ion current intensity of hydrogen also generally increased. However, when the 'methane condition' method was used, the measured δ2H values of the n‐alkanes and n‐fatty acids showed little change under different GC temperature ramp rates.

CONCLUSIONS

Higher pyrolysis efficiency could reduce the tailing of the H2 peak and the related isotopic variations at increased GC temperature ramp rates. In addition, too slow a temperature ramp rate could broaden the peak width and thus increase the background effect and possible isotopic fractionations in the split interface; this could also influence the hydrogen isotope values. We therefore suggest that the appropriate temperature ramp rate is an important factor in improving the precision in analyzing compound‐specific hydrogen isotopes. Copyright © 2012 John Wiley & Sons, Ltd.
Elimination of nitrogen interference during online oxygen isotope analysis of nitrogen‐doped organics using the “NiCat” nickel reduction system
Authors: Hagopian William M. , Jahren A. Hope
Published: July 2012

RATIONALE

Accurate online analysis of the δ18O values of nitrogen‐bearing organic compounds is of interest to several emergent fields, including ecology, forensics and paleontology. During online analysis, high‐temperature conversion (HTC) of nitrogen‐bearing organics produces N2 gas which creates isobaric interference with the isotopic measurement. Specifically, N2 reacts with trace amounts of oxygen in the mass spectrometer source to form 14N16O (m/z 30), which prevents accurate evaluation of the sample 12C18O peak (m/z 30).

METHODS

We present an alternative system to the conventional HTC, which uses a nickel‐catalyzed (“NiCat”) reduction furnace to convert HTC‐produced CO into CO2, allowing for δ18O measurement using signal intensities at m/z 44 and 46.

RESULTS

This system yields identical δ18O values for nitrogen‐doped and undoped sucrose and cellulose compounds up to molar yield ratios of N2:CO = 0.22. In contrast, our conventional HTC system configured to factory recommendations with the stock gas chromatography (GC) column produced a discrepancy of ~5‰ between nitrogen‐doped and undoped samples.

CONCLUSIONS

Because of its ability to eliminate isobaric interference, the NiCat system is a viable alternative to conventional HTC for δ18O measurement, and can be constructed from relatively inexpensive and readily available materials. As an additional advantage, the CO2 analyte produced by NiCat may be cryofocused, to allow for oxygen‐isotope determinations on very small amounts of sample substrate. Copyright © 2012 John Wiley & Sons, Ltd.
RESTORING SALMON HABITAT FOR A CHANGING CLIMATE
Authors: Beechie T. , Imaki H. , Greene J. , Wade A. , Wu H. , Pess G. , Roni P. , Kimball J. , Stanford J. , Kiffney P. , Mantua N.
Published: July 2012

An important question for salmon restoration efforts in the western USA is ‘How should habitat restoration plans be altered to accommodate climate change effects on stream flow and temperature?’ We developed a decision support process for adapting salmon recovery plans that incorporates (1) local habitat factors limiting salmon recovery, (2) scenarios of climate change effects on stream flow and temperature, (3) the ability of restoration actions to ameliorate climate change effects, and (4) the ability of restoration actions to increase habitat diversity and salmon population resilience. To facilitate the use of this decision support framework, we mapped scenarios of future stream flow and temperature in the Pacific Northwest region and reviewed literature on habitat restoration actions to determine whether they ameliorate a climate change effect or increase life history diversity and salmon resilience. Under the climate change scenarios considered here, summer low flows decrease by 35–75% west of the Cascade Mountains, maximum monthly flows increase by 10–60% across most of the region, and stream temperatures increase between 2 and 6°C by 2070–2099. On the basis of our literature review, we found that restoring floodplain connectivity, restoring stream flow regimes, and re‐aggrading incised channels are most likely to ameliorate stream flow and temperature changes and increase habitat diversity and population resilience. By contrast, most restoration actions focused on in‐stream rehabilitation are unlikely to ameliorate climate change effects. Finally, we illustrate how the decision support process can be used to evaluate whether climate change should alter the types or priority of restoration actions in a salmon habitat restoration plan. Copyright © 2012 John Wiley & Sons, Ltd.
Sustainable Organizations: A Simple Matter of Evidence
Authors: Emery Merrelyn
Published: July 2012

In this note, I analyse the latest response by Kira and van Eijnatten in which they claim that fundamentally different ways of looking at reality and profound differences in worldview play a role in this current debate. Their response has three elements, a repetition of their position and two appeals, to authority and to a majority. By basing their response on logical fallacies, their latest note, plus the history of this debate, shows that the real difference is between an approach based on acceptable standards for scientific practices and evidence and one which is not. As evidence takes precedence over fallacies, I pose a question for Kira and van Eijnatten—do they believe the evidence I have presented? I look forward to their answer. Copyright © 2012 John Wiley & Sons, Ltd.
Kiron System, an Integration of Living and Artificial Systems (Buildings Case)
Authors: Curiel‐Carias Ernesto C.
Published: July 2012

Simultaneously satisfying human and environmental demands requires overarching concepts to facilitate the conciliation of such demands. These concepts are particularly necessary in certain regions where, as a result of rapid population growth, a large demand for housing impinges upon vital and sensitive ecosystems. The object of the present paper is to focus on the building concept in natural and rarely disturbed environments. Starting with the organizational logic that underlies living systems, this paper proposes a new hierarchical level of organization or hypothetical Kiron System (KS) that lies between the ecosystem and the human biosystem. The hypothetical system would serve to reconcile the requirements of both systems. From within this new hierarchical level, it is possible to extract the entire concept of the artificial sub‐system (the building) that would make such hypothetical system possible. Finally, the effects of this concept on the various functions of the building are analysed. Copyright © 2012 John Wiley & Sons, Ltd.
Directing Differentiation of Human Embryonic Stem Cells Toward Anterior Neural Ectoderm Using Small Molecules
Authors: Surmacz Beata , Fox Heather , Gutteridge Alex , Lubitz Sandra , Whiting Paul
Published: July 2012

Based on knowledge of early embryo development, where anterior neural ectoderm (ANE) development is regulated by native inhibitors of bone morphogenic protein (BMP) and Nodal/Activin signaling, most published protocols of human embryonic stem cell differentiation to ANE have demonstrated a crucial role for Smad signaling in neural induction. The drawbacks of such protocols include the use of an embryoid body culture step and use of polypeptide secreted factors that are both expensive and, when considering clinical applications, have significant challenges in terms of good manufacturing practices compliancy. The use of small molecules to direct differentiation of pluripotent stem cells toward a specified lineage represents a powerful approach to generate specific cell types for further understanding of biological function, for understanding disease processes, for use in drug discovery, and finally for use in regenerative medicine. We therefore aimed to find controlled and reproducible animal-component-free differentiation conditions that would use only small molecules. Here, we demonstrate that pluripotent stem cells can be reproducibly and efficiently differentiated to PAX6+ (a marker of neuroectoderm) and OCT4− (a marker of pluripotent stem cells) cells with the use of potent small inhibitors of the BMP and Activin/Nodal pathways, and in animal-component-free conditions, replacing the frequently used Noggin and SB431542. We also show by transcript analysis, both at the population level and for the first time at the single-cell level, that differentiated cells express genes characteristic for the development of ANE, in particular for the development of the future forebrain.
Cell‐surface sensors: lighting the cellular environment
Authors: Ali Md Monsur , Kang Dong‐Ku , Tsang Kyle , Fu Moyu , Karp Jeffrey M. , Zhao Weian
Published: July 2012

Cell‐surface sensors are powerful tools to elucidate cell functions including cell signaling, metabolism, and cell‐to‐cell communication. These sensors not only facilitate our understanding in basic biology but also advance the development of effective therapeutics and diagnostics. While genetically encoded fluorescent protein/peptide sensors have been most popular, emerging cell surface sensor systems including polymer‐, nanoparticle‐, and nucleic acid aptamer‐based sensors have largely expanded our toolkits to interrogate complex cellular signaling and micro‐ or nano‐environments. In particular, cell‐surface sensors that interrogate in vivo cellular microenvironments represent an emerging trend in the development of next generation tools which biologists may routinely apply to elucidate cell biology in vivo and to develop new therapeutics and diagnostics. This review focuses on the most recent development in areas of cell‐surface sensors. We will first discuss some recently reported genetically encoded sensors that were used for monitoring cellular metabolites, proteins, and neurotransmitters. We will then focus on the emerging cell surface sensor systems with emphasis on the use of DNA aptamer sensors for probing cell signaling and cell‐to‐cell communication. WIREs Nanomed Nanobiotechnol 2012, 4:547–561. doi: 10.1002/wnan.1179

This article is categorized under:

Diagnostic Tools > Biosensing

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology