bluuebunny/crossref_metadata_2025 huggingface dataset:
An analytical approximation for the orientation-dependent excluded volume of tangent hard sphere chains of arbitrary chain length and flexibility
Authors: van Westen Thijs , Vlugt Thijs J. H. , Gross Joachim
Published: July 2012

Onsager-like theories are commonly used to describe the phase behavior of nematic (only orientationally ordered) liquid crystals. A key ingredient in such theories is the orientation-dependent excluded volume of two molecules. Although for hard convex molecular models this is generally known in analytical form, for more realistic molecular models that incorporate intramolecular flexibility, one has to rely on approximations or on computationally expensive Monte Carlo techniques. In this work, we provide a general correlation for the excluded volume of tangent hard-sphere chains of arbitrary chain length and flexibility. The flexibility is introduced by means of the rod-coil model. The resulting correlation is of simple analytical form and accurately covers a wide range of pure component excluded volume data obtained from Monte Carlo simulations of two-chain molecules. The extension to mixtures follows naturally by applying simple combining rules for the parameters involved. The results for mixtures are also in good agreement with data from Monte Carlo simulations. We have expressed the excluded volume as a second order power series in sin (γ), where γ is the angle between the molecular axes. Such a representation is appealing since the solution of the Onsager Helmholtz energy functional usually involves an expansion of the excluded volume in Legendre coefficients. Both for pure components and mixtures, the correlation reduces to an exact expression in the limit of completely linear chains. The expression for mixtures, as derived in this work, is thereby an exact extension of the pure component result of Williamson and Jackson [Mol. Phys. 86, 819–836 (1995)]10.1080/00268979500102391.
Unrestricted Hartree-Fock based on the fragment molecular orbital method: Energy and its analytic gradient
Authors: Nakata Hiroya , Fedorov Dmitri G. , Nagata Takeshi , Yokojima Satoshi , Ogata Koji , Kitaura Kazuo , Nakamura Shinichiro
Published: July 2012

A consideration of the surrounding environment is necessary for a meaningful analysis of the reaction activity in large molecular systems. We propose an approach to perform unrestricted Hartree-Fock (UHF) calculations within the framework of the fragment molecular orbital (FMO) method (FMO-UHF) to study large systems with unpaired electrons. Prior to an energy analysis one has to optimize geometry, which requires an accurate analytic energy gradient. We derive the FMO-UHF energy and its analytic gradient and implement them into GAMESS. The performance of FMO-UHF is evaluated for a solvated organic molecule and a solvated metal complex, as well as for the active part of a protein, in terms of energy, gradient, and geometry optimization.
Quasi-harmonic approximation of thermodynamic properties of ice Ih, II, and III
Authors: Ramírez R. , Neuerburg N. , Fernández-Serra M.-V. , Herrero C. P.
Published: July 2012

Several thermodynamic properties of ice Ih, II, and III are studied by a quasi-harmonic approximation and compared to results of quantum path integral and classical simulations. This approximation allows to obtain thermodynamic information at a fraction of the computational cost of standard simulation methods, and at the same time permits studying quantum effects related to zero-point vibrations of the atoms. Specifically, we have studied the crystal volume, bulk modulus, kinetic energy, enthalpy, and heat capacity of the three ice phases as a function of temperature and pressure. The flexible q-TIP4P/F model of water was employed for this study, although the results concerning the capability of the quasi-harmonic approximation are expected to be valid independently of the employed water model. The quasi-harmonic approximation reproduces with reasonable accuracy the results of quantum and classical simulations showing an improved agreement at low temperatures (T< 100 K). This agreement does not deteriorate as a function of pressure as long as it is not too close to the limit of mechanical stability of the ice phases.
Fully automated measurement setup for non-destructive characterization of thermoelectric materials near room temperature
Authors: Schwyter E. S. , Helbling T. , Glatz W. , Hierold C.
Published: July 2012

A measurement setup is presented that allows for a complete and non-destructive material characterization of electrochemically deposited thermoelectric material. All electrical (Seebeck coefficient α, electrical conductivity σ), thermal (thermal conductivity λ), and thermoelectric (figure of merit ZT) material parameters are determined within a single measurement run. The setup is capable of characterizing individual electrochemically deposited Bi2+xTe3−x pillars of various size and thickness down to a few 10 μm, embedded in a polymer matrix with a maximum measurement area of 1 × 1 cm2. The temperature range is limited to an application specific window near room temperature of 10 °C to 70 °C. A maximum thermal flux of 1 W/cm2 can be applied to the device under test (DUT) by the Peltier element driven heat source and sink. The setup has a highly symmetric design and DUTs can be mounted and dismounted within few seconds. A novel in situ recalibration method for a simple, quick and more accurate calibration of all sensors has been developed. Thermal losses within the setup are analysed and are mathematically considered for each measurement. All random and systematic errors are encountered for by a MATLAB routine, calculating all the target parameters and their uncertainties. The setup provides a measurement accuracy of ±2.34 μV/K for α, ±810.16 S/m for σ, ±0.13 W/mK for λ, and ±0.0075 for ZT at a mean temperature of 42.5 °C for the specifically designed test samples with a pillar diameter of 696 μm and thickness of 134 μm, embedded in a polyethylene terephthalate polymer matrix.
Incorporation of the stress concentration slots into the flexures for a high-performance microaccelerometer
Authors: Zhao Yulong , Sun Lu , Liu Yan , Wang Weizhong , Tian Bian
Published: July 2012

Presented in this paper is a development of a high-performance piezoresistive microaccelerometer based on the slot etching in the quad flexures for the vibration detection of high speed spindle. The proposed structure consists of a proof mass supported by four thin flexures with slots etched in the middle. Boron diffused piezoresistors located near the stress concentration regions are used for sensing the localized stress resulting from the incorporation of the slots into the flexures. Theoretical analysis and finite element analysis show satisfactory results of an improved sensitivity and favorable natural frequency higher than 10 kHz, conforming to the initial design requirements. The microfabrication techniques are described to prototype the two accelerometer chips, one with slots and the other one without slots. The tested microaccelerometers with 3 V DC power supply show an average sensitivity of 0.424 mV/g normal to the proof mass plane, increased by 60.6% than the ones without slots. An average transverse sensitivity is found to be 9.2 μV/g along X axis and 14.2 μV/g along Y axis, either of which is less than 3.5% of prime-axis sensitivity. Concerning the resonant frequency, dynamic experiment shows about 12.46 kHz and is available for the proposed design with a tiny loss of 3.5% compared with the quad-beam design. When taking the product of sensitivity and natural frequency as judgment criteria, an inspiring increase by 28.6% of the figure of merit is accomplished for the proposed accelerometer. Overall, the findings of this study confirm the feasibility of incorporating slots into the conventional configurations to improve the sensor sensitivity while maintaining a comparatively high natural frequency.
A threshold-based approach to calorimetry in helium droplets: Measurement of binding energies of water clusters
Authors: Lewis William K. , Harruff-Miller Barbara A. , Gord Michael A. , Gord Joseph R. , Guliants Elena A. , Bunker Christopher E.
Published: July 2012

Helium droplet beam methods have emerged as a versatile technique that can be used to assemble a wide variety of atomic and molecular clusters. We have developed a method to measure the binding energies of clusters assembled in helium droplets by determining the minimum droplet sizes required to assemble and detect selected clusters in the spectrum of the doped droplet beam. The differences in the droplet sizes required between the various multimers are then used to estimate the incremental binding energies. We have applied this method to measure the binding energies of cyclic water clusters from the dimer to the tetramer. We obtain measured values of D0 that are in agreement with theoretical estimates to within ∼20%. Our results suggest that this threshold-based approach should be generally applicable using either mass spectrometry or optical spectroscopy techniques for detection, provided that the clusters selected for study are at least as strongly bound as those of water, and that a peak in the overall spectrum of the beam corresponding only to the cluster chosen (at least in the vicinity of the threshold) can be located.
Transport characteristics of AlGaN/GaN/AlGaN double heterostructures with high electron mobility
Authors: Meng Fanna , Zhang Jincheng , Zhou Hao , Ma Juncai , Xue Junshuai , Dang Lisha , Zhang Linxia , Lu Ming , Ai Shan , Li Xiaogang , Hao Yue
Published: July 2012

The AlGaN/GaN/AlGaN double heterostructure (DH) with high electron mobility of 1862 cm2/Vs at room temperature and 478 cm2/Vs at 573 K high temperature was obtained by a combination of optimization schemes considering scattering mechanisms. First, a composite buffer layer structure, including GaN and AlGaN layer, was used to improve the crystal quality of the AlGaN/GaN/AlGaN DH. Second, interface roughness scattering was reduced by increasing the channel thickness, thus the two-dimensional electron gas mobility was further improved. Moreover, an ultrathin AlN interlayer was inserted between the GaN channel layer and the AlGaN buffer layer to decrease the alloy disorder scattering. The Hall effect measurements showed that the DH had better transport characteristics at high temperatures, and an electron mobility of 478 cm2/Vs was achieved at 573 K, which is twice larger than that of the conventional single heterostructure (∼200 cm2/Vs at 573 K). Therefore, AlGaN/GaN/AlGaN DH is more suitable for the applications in high temperature electronic devices.
Fuel management effectiveness in a mixed heathland: a comparison of the effect of different treatment types on fire initiation risk
Authors: Marino Eva , Hernando Carmen , Madrigal Javier , Díez Carmen , Guijarro Mercedes
Published: July 2012

Fuel management is commonly used to reduce fire risk in fire-prone shrubland, but information about the real efficacy of the different techniques is scarce. In this study, we assessed in the laboratory the effects of different treatment types on fire initiation risk in a mixed heathland. The effects of two mechanical treatments and of prescribed burning were compared with untreated vegetation. Flammability tests were performed in samples of the regenerated shrubs and fine ground fuels present 2 years after treatments. Results indicate that all treatments were effective in reducing fire initiation risk in regenerated shrubs, but not in fine ground fuels. Recovery of vegetation differed between treatments, and treatment type had a significant effect on flammability, mainly affecting fire sustainability. Wind speed had a minor effect on shrub fuel flammability, whereas fuel moisture had a significant effect. The flammability of fine ground fuels differed significantly depending on fuel moisture content, even at the low levels tested. Logistic models were fitted to predict successful fire sustainability, and the probability of initial propagation was obtained as a function of treatment type, fuel moisture content and fuel structural characteristics. This study provides new insights into wildfire prevention in shrubland, and compares the effectiveness of different fuel treatment techniques.
A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke
Authors: Overman Justine J. , Clarkson Andrew N. , Wanner Ina B. , Overman William T. , Eckstein Ilya , Maguire Jaime L. , Dinov Ivo D. , Toga Arthur W. , Carmichael S. Thomas
Published: July 2012

Stroke causes loss of neurological function. Recovery after stroke is facilitated by forced use of the affected limb and is associated with sprouting of new connections, a process that is sharply confined in the adult brain. We show that ephrin-A5 is induced in reactive astrocytes in periinfarct cortex and is an inhibitor of axonal sprouting and motor recovery in stroke. Blockade of ephrin-A5 signaling using a unique tissue delivery system induces the formation of a new pattern of axonal projections in motor, premotor, and prefrontal circuits and mediates recovery after stroke in the mouse through these new projections. Combined blockade of ephrin-A5 and forced use of the affected limb promote new and surprisingly widespread axonal projections within the entire cortical hemisphere ipsilateral to the stroke. These data indicate that stroke activates a newly described membrane-bound astrocyte growth inhibitor to limit neuroplasticity, activity-dependent axonal sprouting, and recovery in the adult.
Nucleic acid scavengers inhibit thrombosis without increasing bleeding
Authors: Jain Shashank , Pitoc George A. , Holl Eda K. , Zhang Ying , Borst Luke , Leong Kam W. , Lee Jaewoo , Sullenger Bruce A.
Published: July 2012

Development of effective, yet safe, antithrombotic agents has been challenging because such agents increase the propensity of patients to bleed. Recently, naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphates have been shown to activate blood coagulation. In this report, we evaluate the anticoagulant and antithrombotic activity of nucleic acid-binding polymers in vitro and in vivo. Such polymers bind to DNA, RNA, and inorganic polyphosphate molecules with high affinity and inhibit RNA- and polyphosphate-induced clotting and the activation of the intrinsic pathway of coagulation in vitro. Moreover, [NH
2
(CH
2
)
2
NH
2
]∶(G = 3);dendri PAMAM(NH
2
)
32
(PAMAM G-3) prevents thrombosis following carotid artery injury and pulmonary thromboembolism in mice without significantly increasing blood loss from surgically challenged animals. These studies indicate that nucleic acid-binding polymers are able to scavenge effectively prothrombotic nucleic acids and other polyphosphates in vivo and represent a new and potentially safer class of antithrombotic agents.
Hypoxia suppresses conversion from proliferative arrest to cellular senescence
Authors: Leontieva Olga V. , Natarajan Venkatesh , Demidenko Zoya N. , Burdelya Lyudmila G. , Gudkov Andrei V. , Blagosklonny Mikhail V.
Published: July 2012

Unlike reversible quiescence, cellular senescence is characterized by a large flat cell morphology, β-gal staining and irreversible loss of regenerative (i.e., replicative) potential. Conversion from proliferative arrest to irreversible senescence, a process named geroconversion, is driven in part by growth-promoting pathways such as mammalian target of rapamycin (mTOR). During cell cycle arrest, mTOR converts reversible arrest into senescence. Inhibitors of mTOR can suppress geroconversion, maintaining quiescence instead. It was shown that hypoxia inhibits mTOR. Therefore, we suggest that hypoxia may suppress geroconversion. Here we tested this hypothesis. In HT-p21-9 cells, expression of inducible p21 caused cell cycle arrest without inhibiting mTOR, leading to senescence. Hypoxia did not prevent p21 induction and proliferative arrest, but instead inhibited the mTOR pathway and geroconversion. Exposure to hypoxia during p21 induction prevented senescent morphology and loss of regenerative potential, thus maintaining reversible quiescence so cells could restart proliferation after switching p21 off. Suppression of geroconversion was p53- and HIF-1–independent, as hypoxia also suppressed geroconversion in cells lacking functional p53 and HIF-1α. Also, in normal fibroblasts and retinal cells, hypoxia inhibited the mTOR pathway and suppressed senescence caused by etoposide without affecting DNA damage response, p53/p21 induction and cell cycle arrest. Also hypoxia suppressed geroconversion in cells treated with nutlin-3a, a nongenotoxic inducer of p53, in cell lines susceptible to nutlin-3a–induced senescence (MEL-10, A172, and NKE). Thus, in normal and cancer cell lines, hypoxia suppresses geroconversion caused by diverse stimuli. Physiological and clinical implications of the present findings are discussed.
Fungal endophyte communities reflect environmental structuring across a Hawaiian landscape
Authors: Zimmerman Naupaka B. , Vitousek Peter M.
Published: July 2012

We surveyed endophytic fungal communities in leaves of a single tree species (
Metrosideros polymorpha
) across wide environmental gradients (500–5,500 mm of rain/y; 10–22 °C mean annual temperature) spanning short geographic distances on Mauna Loa Volcano, Hawai’i. Using barcoded amplicon pyrosequencing at 13 sites (10 trees/site; 10 leaves/tree), we found very high levels of diversity within sites (a mean of 551 ± 134 taxonomic units per site). However, among-site diversity contributed even more than did within-site diversity to the overall richness of more than 4,200 taxonomic units observed in
M. polymorpha
, and this among-site variation in endophyte community composition correlated strongly with temperature and rainfall. These results are consistent with suggestions that foliar endophytic fungi are hyperdiverse. They further suggest that microbial diversity may be even greater than has been assumed and that broad-scale environmental controls such as temperature and rainfall can structure eukaryotic microbial diversity. Appropriately constrained study systems across strong environmental gradients present a useful means to understand the environmental factors that structure the diversity of microbial communities.
Quantum rotation of
ortho
and
para
-water encapsulated in a fullerene cage
Authors: Beduz Carlo , Carravetta Marina , Chen Judy Y.-C. , Concistrè Maria , Denning Mark , Frunzi Michael , Horsewill Anthony J. , Johannessen Ole G. , Lawler Ronald , Lei Xuegong , Levitt Malcolm H. , Li Yongjun , Mamone Salvatore , Murata Yasujiro , Nagel Urmas , Nishida Tomoko , Ollivier Jacques , Rols Stéphane , Rõõm Toomas , Sarkar Riddhiman , Turro Nicholas J. , Yang Yifeng
Published: July 2012

Inelastic neutron scattering, far-infrared spectroscopy, and cryogenic nuclear magnetic resonance are used to investigate the quantized rotation and
ortho–para
conversion of single water molecules trapped inside closed fullerene cages. The existence of metastable
ortho
-water molecules is demonstrated, and the interconversion of
ortho
-and
para
-water spin isomers is tracked in real time. Our investigation reveals that the ground state of encapsulated
ortho
water has a lifted degeneracy, associated with symmetry-breaking of the water environment.
Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion
Authors: Artemenko Yulia , Batsios Petros , Borleis Jane , Gagnon Zachary , Lee Josephine , Rohlfs Meino , Sanséau Doriane , Willard Stacey S. , Schleicher Michael , Devreotes Peter N.
Published: July 2012

Chemotaxis depends on a network of parallel pathways that coordinate cytoskeletal events to bias cell movement along a chemoattractant gradient. Using a forward genetic screen in
Dictyostelium discoideum
, we identified the Ste20 kinase KrsB, a homolog of tumor suppressors Hippo and MST1/2, as a negative regulator of cell spreading and substrate attachment. The excessive adhesion of
krsB
−
cells reduced directional movement and prolonged the streaming phase of multicellular aggregation. These phenotypes depended on an intact kinase domain and phosphorylation of a conserved threonine (T176) within the activation loop. Chemoattractants triggered a rapid, transient autophosphorylation of T176 in a heterotrimeric G protein-dependent and PI3K- and TorC2-independent manner. The active phosphorylated form of KrsB acts to decrease adhesion to the substrate. Taken together these studies suggest that cycling between active and inactive forms of KrsB may provide the dynamic regulation of cell adhesion needed for proper cell migration and chemotaxis. KrsB interacts genetically with another
D. discoideum
Hippo/MST homolog, KrsA, but the two genes are not functionally redundant. These studies show that Hippo/MST proteins, like the tumor suppressor PTEN and oncogenes Ras and PI3K, play a key role in cell morphological events in addition to their role in regulating cell growth.
Ionized metal flux fraction measurements in HiPIMS discharges
Authors: Poolcharuansin P , Bowes M , Petty T J , Bradley J W
Published: July 2012

Using a biased quartz crystal microbalance in combination with a gridded electrode, the ionized metal flux fraction in a high power impulse magnetron sputtering (HiPIMS) discharge operated with a titanium target has been investigated. The average discharge power was controlled by varying three different parameters; initial target voltage, pulse width and pulse frequency. The average discharge power was varied from 0.3 to 1.3 kW and irrespective of the power control method used an associated decrease in the flux fraction (from 50% to 30%) was observed. The mechanisms responsible for this decrease in the time-averaged flux fraction of metal ions are discussed.
PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells
Authors: Shibata Takuma , Takemura Naoki , Motoi Yuji , Goto Yoshiyuki , Karuppuchamy Thangaraj , Izawa Kumi , Li Xiaobing , Akashi-Takamura Sachiko , Tanimura Natsuko , Kunisawa Jun , Kiyono Hiroshi , Akira Shizuo , Kitamura Toshio , Kitaura Jiro , Uematsu Satoshi , Miyake Kensuke
Published: July 2012

AbstractToll-like receptor 5 (TLR5), a sensor for bacterial flagellin, mounts innate and adaptive immune responses, and has been implicated in infectious diseases, colitis and metabolic syndromes. Although TLR5 is believed to belong to cell surface TLRs, cell surface expression has never been verified. Moreover, it has remained unclear which types of immune cells express TLR5 and contribute to flagellin-dependent responses. In this study we established an anti-mouse TLR5 monoclonal antibody and studied the cell surface expression of TLR5 on immune cells. The macrophage cell line J774 expressed endogenous TLR5 on the cell surface and produced IL-6 and G-CSF in response to flagellin. Cell surface expression of TLR5 and flagellin-induced responses were completely abolished by silencing a TLR-specific chaperone protein associated with TLR4 A (PRAT4A), demonstrating that TLR5 is another client of PRAT4A. In the in vivo immune cells, cell surface TLR5 was mainly found on neutrophils and CD11bhiLy6Chiclassical monocytes in the bone marrow, circulation, spleen and inflammatory lesions. Ly6Chiclassical monocytes, but not neutrophils, produced cytokines in response to flagellin. Splenic CD8−CD4+conventional dendritic cells and CD11chiCD11bhilamina propria DCs, also clearly expressed cell surface TLR5. Collectively, cell surface expression of TLR5 is dependent on PRAT4A and restricted to neutrophils, classical monocytes and specific DC subsets.
Takeover Bidding and Shareholder Information
Authors: Marquez Robert , Yılmaz Bilge
Published: July 2012

We study the role of shareholder information during the acquisition of widely held firms. When target shareholders share the same information about the post-takeover value, increasing the precision of information has no effect on the expected acquisition price. However, more precise information aggravates the free-rider problem, allowing shareholders to better discern when it is worthwhile to hold out rather than tender their shares. By contrast, when information is dispersed among shareholders, providing shareholders with superior information induces the raider to offer higher prices, thus increasing shareholder value. However, in this case, neither prices nor tendering decisions aggregate any information. (JEL G34, D82)
Assembly of the viroplasm by viral non-structural protein Pns10 is essential for persistent infection of rice ragged stunt virus in its insect vector
Authors: Jia Dongsheng , Guo Nianmei , Chen Hongyan , Akita Fusamichi , Xie Lianhui , Omura Toshihiro , Wei Taiyun
Published: July 2012

Rice ragged stunt virus (RRSV), an oryzavirus, is transmitted by brown planthopper in a persistent propagative manner. In this study, sequential infection of RRSV in the internal organs of its insect vector after ingestion of virus was investigated by immunofluorescence microscopy. RRSV was first detected in the epithelial cells of the midgut, from where it proceeded to the visceral muscles surrounding the midgut, then throughout the visceral muscles of the midgut and hindgut, and finally into the salivary glands. Viroplasms, the sites of virus replication and assembly of progeny virions, were formed in the midgut epithelium, visceral muscles and salivary glands of infected insects and contained the non-structural protein Pns10 of RRSV, which appeared to be the major constituent of the viroplasms. Viroplasm-like structures formed in non-host insect cells following expression of Pns10 in a baculovirus system, suggesting that the viroplasms observed in RRSV-infected cells were composed basically of Pns10. RNA interference induced by ingestion of dsRNA from the Pns10 gene of RRSV strongly inhibited such viroplasm formation, preventing efficient virus infection and spread in its insect vectors. These results show that Pns10 of RRSV is essential for viroplasm formation and virus replication in the vector insect.
Specific cell tropism and neutralization of human parechovirus types 1 and 3: implications for pathogenesis and therapy development
Authors: Westerhuis Brenda M. , Koen Gerrit , Wildenbeest Joanne G. , Pajkrt Dasja , de Jong Menno D. , Benschop Kimberley S. M. , Wolthers Katja C.
Published: July 2012

Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is associated with mild disease, HPeV3 is the cause of neonatal sepsis and meningitis. To test whether in vitro replication kinetics of HPeV1 and HPeV3 could be related to pathogenicity, HPeV1 and HPeV3 strains isolated from patients were cultured on cell lines of gastrointestinal, respiratory and neural origin, and replication kinetics were measured by real-time PCR. No relationship was found between clinical symptoms and in vitro replication of the HPeV1 strains. In contrast, the HPeV3 strains showed faster replication in neural cells and there was a relationship between higher in vitro replication kinetics and neuropathogenicity in the patient. Furthermore, HPeV1 could be neutralized efficiently by its specific antibody and by intravenous immunoglobulins (IVIG), while most HPeV3 strains could not be neutralized. In IVIG, very low neutralizing antibody (nAb) titres against HPeV3 were found. Additionally, very low nAb titres were observed in sera of two HPeV3-infected donors, while high nAb titres against HPeV1 could be detected. Our data suggest that the mild clinical course of HPeV1 infection is primarily influenced by strong nAb responses, while HPeV3 might be difficult to neutralize in vivo and therefore the course of infection will mainly be determined by in vivo cell tropism.
Hantaviruses in rodents and humans, Xi’an, PR China
Authors: Ma Chaofeng , Yu Pengbo , Nawaz Muhammad , Zuo Shuqing , Jin Tiezhi , Li Yanli , Li Jinsong , Li Hengxin , Xu Jiru
Published: July 2012

Xi’an, the capital of Shaanxi province, located in north-west China, is one of the major endemic areas for haemorrhagic fever with renal syndrome (HFRS). In this study, the epidemiological data of HFRS in Xi’an from 1959 to 2010, especially in the past ten years (2001–2010), were surveyed. The features of hantavirus (HV) host carriers, the molecular characteristics of the HV S gene from hosts and patients, and the genome of the viral isolate were also investigated. Data showed that there might be a ten-year cycle of HFRS in Xi’an. Although the main population group infected over the past ten years was still the 16–59-year-old male farmers, the composition of the population and geographical distribution of HFRS cases have changed slowly, accompanied by the development of environmental and socio-economic situations. Apodemus agrarius remains the dominant host of HV. The HV strains from host rodents and patients in Xi’an belonged to the Hantaan virus (HTNV); no Seoul virus strains were found. Phylogenetic analysis of the small segments of strains taken from hosts and patients, and the whole genome of a viral isolate showed that the virus circulating in Xi’an had high similarity to Guizhou strains. The study also indicated that the vaccine candidate strain A16 isolated during the past century in Xi’an might be a recombinant strain of HTNV and the Amur virus, thus it may not be an optimal vaccine strain.
Rescue of a genotype 4 human hepatitis E virus from cloned cDNA and characterization of intergenotypic chimeric viruses in cultured human liver cells and in pigs
Authors: Córdoba Laura , Feagins Alicia R. , Opriessnig Tanja , Cossaboom Caitlin M. , Dryman Barbara A. , Huang Yao-Wei , Meng Xiang-Jin
Published: July 2012

Hepatitis E virus (HEV) is an important but extremely understudied human pathogen. Genotypes 1 and 2 are restricted to humans, whereas genotypes 3 and 4 are zoonotic, infecting both humans and pigs. This report describes, for the first time, the successful rescue of infectious HEV in vitro and in vivo from cloned cDNA of a genotype 4 human HEV (strain TW6196E). The complete genomic sequence of the TW6196E virus was determined and a full-length cDNA clone (pHEV-4TW) was assembled. Capped RNA transcripts from the pHEV-4TW clone were replication competent in Huh7 cells and infectious in HepG2/C3A cells. Pigs inoculated intrahepatically with capped RNA transcripts from pHEV-4TW developed an active infection, as evidenced by faecal virus shedding and seroconversion, indicating the successful rescue of infectious genotype 4 HEV and cross-species infection of pigs by a genotype 4 human HEV. To demonstrate the utility of the genotype 4 HEV infectious clone and to evaluate the potential viral determinant(s) for species tropism, four intergenotypic chimeric clones were constructed by swapping various genomic regions between genotypes 1 and 4, and genotypes 1 and 3. All four chimeric clones were replication competent in Huh7 cells, but only the two chimeras with sequences swapped between genotypes 1 and 4 human HEVs produced viruses capable of infecting HepG2/C3A cells. None of the four chimeras was able to establish a robust infection in pigs. The availability of a genotype 4 HEV infectious clone affords an opportunity to delineate the molecular mechanisms of HEV cross-species infection in the future.
Local Treatment of Hand-Foot Syndrome with Uridine/Thymidine:In VitroAppraisal on a Human Keratinocyte Cell Line HaCaT
Authors: Hartinger J. , Veselý P. , Matoušková E. , Argalacsová S. , Petruželka L. , Netíková I.
Published: July 2012

5-fluorouracil (5-FU) is one of the most commonly used antineoplastic drugs in the anticancer therapy. The hand-foot (HF) syndrome (palmar-plantar erythrodysesthesia) is an adverse effect frequently related to long-term i.v. administration of 5-FU or its orally applicable prodrug capecitabine. Its severity can even lead to interruption of the otherwise effective anticancer therapy. Tentative practice in some clinics has shown that topical application of 10% uridine ointment is beneficial for calming down the HF syndrome. This study is focused on verifying the alleged protective activity of uridine in thein vitromodel of cultured human keratinocyte cell line HaCaT. We also tested the protective effects of thymidine alone or uridine-thymidine combination. The cellular viability time progression was measured in order to evaluate the effect of protective agents by three different types of cytopathogenicity tests—NTCA test (non-destructive test of cellular activity), modified MTT test and RTCA (real-time cell analyser, Roche). All three methods proved the ability of uridine and uridine-thymidine combination to protect keratinocytes against 5-FU damagein vitro. While thymidine alone did not show any remarkable effect, the thymidine-uridine combination demonstrated enhanced protective activity compared to uridine alone. Our findings provided the supporting rationale for using uridine or uridine-thymidine ointments in the HF syndrome local therapy.
A Comparison of Third-Generation Semi-Invasive Arterial Waveform Analysis with Thermodilution in Patients Undergoing Coronary Surgery
Authors: Broch Ole , Renner Jochen , Gruenewald Matthias , Meybohm Patrick , Schöttler Jan , Steinfath Markus , Malbrain Manu , Bein Berthold
Published: July 2012

Uncalibrated semi-invasive continous monitoring of cardiac index (CI) has recently gained increasing interest. The aim of the present study was to compare the accuracy of CI determination based on arterial waveform analysis with transpulmonary thermodilution. Fifty patients scheduled for elective coronary surgery were studied after induction of anaesthesia and before and after cardiopulmonary bypass (CPB), respectively. Each patient was monitored with a central venous line, the PiCCO system, and the FloTrac/Vigileo-system. Measurements included CI derived by transpulmonary thermodilution and uncalibrated semi-invasive pulse contour analysis. Percentage changes of CI were calculated. There was a moderate, but significant correlation between pulse contour CI and thermodilution CI both before (r2=0.72,P<0.0001) and after (r2=0.62,P<0.0001) CPB, with a percentage error of 31% and 25%, respectively. Changes in pulse contour CI showed a significant correlation with changes in thermodilution CI both before (r2=0.52,P<0.0001) and after (r2=0.67,P<0.0001) CPB. Our findings demonstrated that uncalibrated semi-invasive monitoring system was able to reliably measure CI compared with transpulmonary thermodilution in patients undergoing elective coronary surgery. Furthermore, the semi-invasive monitoring device was able to track haemodynamic changes and trends.
Fast Isogenic Mapping-by-Sequencing of Ethyl Methanesulfonate-Induced Mutant Bulks
Authors: Hartwig Benjamin , James Geo Velikkakam , Konrad Kathryn , Schneeberger Korbinian , Turck Franziska
Published: July 2012

Mapping-by-sequencing (or SHOREmapping) has revitalized the powerful concept of forward genetic screens in plants. However, as in conventional genetic mapping approaches, mapping-by-sequencing requires phenotyping of mapping populations established from crosses between two diverged accessions. In addition to the segregation of the focal phenotype, this introduces natural phenotypic variation, which can interfere with the recognition of quantitative phenotypes. Here, we demonstrate how mapping-by-sequencing and candidate gene identification can be performed within the same genetic background using only mutagen-induced changes as segregating markers. Using a previously unknown suppressor of mutants of like heterochromatin protein1 (lhp1), which in its functional form is involved in chromatin-mediated gene repression, we identified three closely linked ethyl methanesulfonate-induced changes as putative candidates. In order to assess allele frequency differences between such closely linked mutations, we introduced deep candidate resequencing using the new Ion Torrent Personal Genome Machine sequencing platform to our mutant identification pipeline and thereby reduced the number of causal candidate mutations to only one. Genetic analysis of two independent additional alleles confirmed that this mutation was causal for the suppression of lhp1.
Design, Synthesis and Fungicidal Activity of Novel Sclerotiorin Derivatives
Authors: Lin Long , Mulholland Nick , Huang Shao‐Wei , Beattie David , Irwin Dianne , Gu Yu‐Cheng , Clough John , Wu Qiong‐You , Yang Guang‐Fu
Published: July 2012

Sclerotiorin, a chlorine‐containing azaphilone‐type natural product, was first isolated from Penicillium sclerotiorum and has been reported to exhibit weak fungicidal activity. Optimization of the substituents at the 3‐ and 5‐positions of the sclerotiorin framework was investigated with the aim of discovering novel fungicides with improved activity. The design of sclerotiorin analogues involved replacing the diene side chain with a phenyl group or an aromatic‐ or heteroaromatic‐containing aliphatic side chain. The designed compounds were synthesized by cycloisomerization and subsequent oxidation of suitable 2‐alkynylbenzaldehydes, in which a variety of substituents were introduced using a Sonogashira coupling reaction. The structures of these newly prepared compounds were confirmed by 1H and 13C NMR spectroscopy, HRMS and single‐crystal X‐ray analysis. The antifungal activity of the synthesized compounds was evaluated against seven phytopathogenic species. Compounds 3, 9g and 9h were found to have a broad spectrum of fungicidal activity, and these structurally simpler products can be recognized as lead compounds for further optimization.
Computational Studies of Novel Chymase Inhibitors Against Cardiovascular and Allergic Diseases: Mechanism and Inhibition
Authors: Arooj Mahreen , Thangapandian Sundarapandian , John Shalini , Hwang Swan , Park Jong K. , Lee Keun W.
Published: July 2012

To provide a new idea for drug design, a computational investigation is performed on chymase and its novel 1,4‐diazepane‐2,5‐diones inhibitors that explores the crucial molecular features contributing to binding specificity. Molecular docking studies of inhibitors within the active site of chymase were carried out to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism. The density functional theory method was used to optimize molecular structures with the subsequent analysis of highest occupied molecular orbital, lowest unoccupied molecular orbital, and molecular electrostatic potential maps, which revealed that negative potentials near 1,4‐diazepane‐2,5‐diones ring are essential for effective binding of inhibitors at active site of enzyme. The Bayesian model with receiver operating curve statistic of 0.82 also identified arylsulfonyl and aminocarbonyl as the molecular features favoring and not favoring inhibition of chymase, respectively. Moreover, genetic function approximation was applied to construct 3D quantitative structure–activity relationships models. Two models (genetic function approximation model 1 r2 = 0.812 and genetic function approximation model 2 r2 = 0.783) performed better in terms of correlation coefficients and cross‐validation analysis. In general, this study is used as example to illustrate how combinational use of 2D/3D quantitative structure–activity relationships modeling techniques, molecular docking, frontier molecular orbital density fields (highest occupied molecular orbital and lowest unoccupied molecular orbital), and molecular electrostatic potential analysis may be useful to gain an insight into the binding mechanism between enzyme and its inhibitors.
Smoking prevalence and beliefs on smoking cessation among members of the Japanese Cancer Association in 2006 and 2010
Authors: Kumiko Saika , Tomotaka Sobue , Masakazu Nakamura , Akira Oshima , Keiji Wakabayashi , Nobuyuki Hamajima , Yumiko Mochizuki , Rie Yamaguchi , Kazuo Tajima
Published: July 2012

Smoking is a significant contributing factor to disease‐related deaths worldwide. Members of the Japanese Cancer Association (JCA) can play a leading role in helping people to live tobacco‐free through social action. In 2010, this study assessed smoking prevalence among JCA members and their attitudes toward smoking, smoking cessation, and their responsibilities. Results of the 2010 survey were compared with those of a 2006 survey. Final response rates were 60.8% in the 2006 survey and 47.4% in the 2010 survey, and the current smoking rates were 9.0% and 5.3%, respectively. Regarding concern by current smokers over smoking cessation, the percentage of smokers who were ready to quit smoking within the next month increased from 4.9% to 6.3% between 2006 and 2010. Most JCA members agreed with antismoking actions such as smoking bans in all workplaces, public places, or while walking in the street, regulation restricting the sale and distribution of tobacco to children, tobacco education at school, use of tobacco tax for health, provision of information on tobacco, and smoking cessation support. Approximately 30% of responders disagreed on actions to raise the price of tobacco, regulations restricting the sale of tobacco, health warnings on tobacco packaging, bans on tobacco advertisement, and antismoking campaigns. Barriers to smoking cessation interventions identified were physician's time required to provide interventions, resistance of patients to smoking cessation advice, and lack of education on tobacco control. Not only antismoking actions but also support of smokers by health professionals through adequate education on smoking cessation treatment is needed in the future. (Cancer Sci 2012; 103: 1595–1599)
Observations on the relationship between anxiety and depressive symptoms during the course of depressive illnesses.
Authors: Russell GF , De Silva P.
Published: July 2012

1 Roth et al. (1972) have proposed that within the affective disorders there are two distinct syndromes‐anxiety and depression‐ differentiated by the relative predominance of these symptoms, the presence or absence of premorbid maladaptive traits, and the natural outcome of the disorder. 2 Goldberg (1982) on the other hand has suggested that there is a substantial overlap between the two syndromes, and the symptoms of anxiety and depression correlate highly with each other. 3 Patients tend to be treated with an anxiolytic or an antidepressant drug according to the predominance of anxiety or depressive symptoms. 4 There is conflicting evidence regarding the relative effectiveness of tricyclic antidepressants in psychotic (or endogenous) and neurotic (or reactive) depressive illness. Paykel (1972), however, found that the psychotic‐neurotic dichotomy was not helpful in predicting outcome, whereas anxious depressives tended to respond poorly. 5 In three patients with affective illness, tested at regular intervals over the course of several weeks, anxiety and depressive symptoms fluctuated in a way which suggested that they were yoked to each other. A worsening indicated simultaneous deterioration of these symptoms. When they improved, this may have been due to the beneficial effects of the antidepressant drug administered. These findings suggest that antidepressants act, or fail to act, in a fundamental manner on the illness itself rather than on individual symptoms.
The place of anxiety in depressive symptomatology.
Authors: Widlocher D. , Lecrubier Y. , Le Goc Y.
Published: July 2012

1 In the same sample of 42 depressed inpatients, treated by a sequence of anxiolytic followed by antidepressant, total depression, anxiety and retardation scores are compared. 2 Results confirm that retarded patients are good responders to antidepressants. Non‐retarded patients do not respond to antidepressants but respond partially to anxiolytics. 3 The respective place of retardation and anxiety in depression is discussed.
The potential therapeutic role of the enantiomers and metabolites of mianserin.
Authors: Pinder RM , Van Delft AM
Published: July 2012

1 S(+)‐mianserin is the more potent enantiomer of mianserin in pharmacological tests indicative for antidepressant activity. Pharmacological tests indicative for sedation suggest that sedative effects are similar for mianserin and its enantiomers. 2 Of the three compounds, mianserin had the optimal therapeutic ratio of antidepressant‐like activity versus sedative properties when assessed by computerised EEG in healthy volunteers participating in a double‐ blind placebo‐controlled single dose trial. 3 Of the known metabolites, desmethylmianserin and 8‐hydroxymianserin substantially retain pharmacological properties indicative for antidepressant activity but are less active than mianserin in tests indicative for sedation. Mianserin‐N‐oxide is inactive or only weakly active in most pharmacological tests. 4 Desmethylmianserin occurs in human plasma after both single and multiple dosage to an extent of about one‐third that of mianserin. 5 Mianserin has optimal efficacy as the racemate. Desmethylmianserin and 8‐hydroxymianserin are pharmacologically active metabolites and may contribute to the overall antidepressant effects of mianserin.
Mianserin and convulsive seizures.
Authors: Edwards JG , Glen‐Bott M.
Published: July 2012

1 Forty patients have been reported to the Committee on Safety of Medicines (CSM) because of convulsions occurring during treatment with mianserin, suggesting that this drug is more epileptogenic than tricyclic antidepressants. 2 Details concerning 83% of these cases were obtained in a questionnaire study carried out in collaboration with the CSM and compared with those of a control group. 3 Ratings of the relationship between drug and effect carried out by neurologists and J.G.E. showed considerable variations and confidence of a causal connection in only a minority of patients. 4 As the CSM data do not allow for a reliable assessment of the relative epileptogenic effects of antidepressants, a comparison has been made between unpublished work on seizures occurring during treatment with imipramine and amitriptyline and published research on mianserin. This suggests that mianserin is no more epileptogenic than tricyclic antidepressants. 5 Factors that might predispose to seizures include relevant family and past medical history, starting treatment, a change in dose, benzodiazepine withdrawal and concomitant treatment with other drugs that have epileptogenic properties.
Assessment of the interaction between mianserin and centrally‐acting antihypertensive drugs.
Authors: Elliott HL , Whiting B. , Reid JL
Published: July 2012

1 The interaction between mianserin and centrally‐acting antihypertensive drugs was evaluated in normal volunteers and in patients with essential hypertension receiving either clonidine or methyldopa. 2 The administration of the first dose of 20 mg mianserin to the normal volunteers was associated with a significant sedative effect and transient postural hypotension. 3 In the normal volunteers, the blood pressure responses to a single oral dose of 300 micrograms clonidine were not modified by pretreatment with mianserin. The bradycardia associated with clonidine alone, however, was significantly attenuated. 4 In the patient study, no significant changes in blood pressure control were observed, either after the first dose of 30 mg mianserin or after one and two weeks' continued treatment with mianserin. 5 There is no evidence from these studies that the addition of mianserin therapy results in a clinically significant impairment of the antihypertensive effects of clonidine or methyldopa.
Inhibition of pentagastrin‐stimulated and overnight gastric secretion by mianserin.
Authors: Wilson JA , Read J.R. , Boyd EJ , Wormsley KG
Published: July 2012

1 The effects of mianserin (60 mg) have been studied on nocturnal and pentagastrin‐stimulated gastric secretion. 2 Mianserin reduced pentagastrin‐stimulated gastric acid secretion by 38%, pepsin by 40% and secretory volume by 45% during a 1 h test. 3 Twelve‐hour overnight secretion of acid was reduced by 37%, while secretion of pepsin was reduced by 43% and secretory volume by 51%. 4 No adverse effects were noted. 5 These findings, which achieve statistical significance, suggest the need for further study to evaluate the possible role of mianserin in the therapy of duodenal ulcer disease.