bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly tunable hybrid metamaterials employing split-ring resonators strongly coupled to graphene surface plasmons
Authors: Liu Peter Q. , Luxmoore Isaac J. , Mikhailov Sergey A. , Savostianova Nadja A. , Valmorra Federico , Faist Jérôme , Nash Geoffrey R.
Published: November 2015

Metamaterials and plasmonics are powerful tools for unconventional manipulation and harnessing of light. Metamaterials can be engineered to possess intriguing properties lacking in natural materials, such as negative refractive index. Plasmonics offers capabilities of confining light in subwavelength dimensions and enhancing light–matter interactions. Recently, the technological potential of graphene-based plasmonics has been recognized as the latter features large tunability, higher field-confinement and lower loss compared with metal-based plasmonics. Here, we introduce hybrid structures comprising graphene plasmonic resonators coupled to conventional split-ring resonators, thus demonstrating a type of highly tunable metamaterial, where the interaction between the two resonances reaches the strong-coupling regime. Such hybrid metamaterials are employed as high-speed THz modulators, exhibiting ∼60% transmission modulation and operating speed in excess of 40 MHz. This device concept also provides a platform for exploring cavity-enhanced light–matter interactions and optical processes in graphene plasmonic structures for applications including sensing, photo-detection and nonlinear frequency generation.
Genetic control of morphometric diversity in the maize shoot apical meristem
Authors: Leiboff Samuel , Li Xianran , Hu Heng-Cheng , Todt Natalie , Yang Jinliang , Li Xiao , Yu Xiaoqing , Muehlbauer Gary J. , Timmermans Marja C. P. , Yu Jianming , Schnable Patrick S. , Scanlon Michael J.
Published: November 2015

The maize shoot apical meristem (SAM) comprises a small pool of stem cells that generate all above-ground organs. Although mutational studies have identified genetic networks regulating SAM function, little is known about SAM morphological variation in natural populations. Here we report the use of high-throughput image processing to capture rich SAM size variation within a diverse maize inbred panel. We demonstrate correlations between seedling SAM size and agronomically important adult traits such as flowering time, stem size and leaf node number. Combining SAM phenotypes with 1.2 million single nucleotide polymorphisms (SNPs) via genome-wide association study reveals unexpected SAM morphology candidate genes. Analyses of candidate genes implicated in hormone transport, cell division and cell size confirm correlations between SAM morphology and trait-associated SNP alleles. Our data illustrate that the microscopic seedling SAM is predictive of adult phenotypes and that SAM morphometric variation is associated with genes not previously predicted to regulate SAM size.
Deterioration of the coercivity due to the diffusion induced interface layer in hard/soft multilayers
Authors: Si Wenjing , Zhao G. P. , Ran N. , Peng Y. , Morvan F. J. , Wan X. L.
Published: November 2015

Hard/soft permanent magnets have aroused many interests in the past two decades because of their potential in achieving giant energy products as well as their rich variety of magnetic behaviors. Nevertheless, the experimental energy products are much smaller than the theoretical ones due to the much smaller coercivity measured in the experiments. In this paper, the deterioration of the coercivity due to the interface atomic diffusion is demonstrated based on a three dimensional (3D) micromagnetic software (OOMMF) and a formula derived for the pinning field in a hard/soft multilayer, which can be applied to both permanent magnets and exchange-coupled-composite (ECC) media. It is found that the formation of the interface layer can decrease the coercivity by roughly 50%, which is responsible for the observed smaller coercivity in both composite and single-phased permanent magnets. A method to enhance the coercivity in these systems is proposed based on the discussions, consistent with recent experiments where excellent magnetic properties are achieved.
Direct Measurement of Optical Force Induced by Near-Field Plasmonic Cavity Using Dynamic Mode AFM
Authors: Guan Dongshi , Hang Zhi Hong , Marcet Zsolt , Liu Hui , Kravchenko I. I. , Chan C. T. , Chan H. B. , Tong Penger
Published: November 2015

Plasmonic nanostructures have attracted much attention in recent years because of their potential applications in optical manipulation through near-field enhancement. Continuing experimental efforts have been made to develop accurate techniques to directly measure the near-field optical force induced by the plasmonic nanostructures in the visible frequency range. In this work, we report a new application of dynamic mode atomic force microscopy (DM-AFM) in the measurement of the enhanced optical force acting on a nano-structured plasmonic resonant cavity. The plasmonic cavity is made of an upper gold-coated glass sphere and a lower quartz substrate patterned with an array of subwavelength gold disks. In the near-field when the sphere is positioned close to the disk array, plasmonic resonance is excited in the cavity and the induced force by a 1550 nm infrared laser is found to be increased by an order of magnitude compared with the photon pressure generated by the same laser light. The experiment demonstrates that DM-AFM is a powerful tool for the study of light induced forces and their enhancement in plasmonic nanostructures.
Importance of Oceanian small mountainous rivers (SMRs) in global land-to-ocean output of lignin and modern biospheric carbon
Authors: Bao Hongyan , Lee Tsung-Yu , Huang Jr-Chuan , Feng Xiaojuan , Dai Minhan , Kao Shuh-Ji
Published: November 2015

The land-to-ocean export of particulate organic carbon (POC) connects carbon flow from the atmosphere through land to the ocean, of which the contemporary fraction that reaches the deep sea for burial may effectively affect atmospheric CO2. In this regard, small mountainous rivers (SMRs) in Oceania, a global erosion hotspot driven by torrential typhoon rain and active earthquakes are potentially important. Here we measured typhoon lignin discharges for Taiwan SMRs. We found that the particulate lignin export in 96 hours by a single SMR amounting to ~20% of the annual export by Mississippi River. The yearly particulate lignin discharge from Taiwan Island (35,980 km2) is governed by the frequency and magnitude of typhoon; thus, the historical lignin export ranged widely from 1.5 to 99.7 Gg yr−1, which resulted in a 10–100 times higher areal yield relative to non-Oceanian rivers. The lignin-derived modern POC output from Oceania region is 37 ± 21 Tg C yr−1, account for approximately 20% of the annual modern POC export from global rivers. Coupled with the hyperpycnal pathway, the forested watersheds of SMRs in Oceania may serve as a giant factory to rapidly produce and efficiently convey modern POC into deep sea for sequestration.
An anthrax toxin variant with an improved activity in tumor targeting
Authors: Wein Alexander N. , Peters Diane E. , Valivullah Zaheer , Hoover Benjamin J. , Tatineni Aparna , Ma Qian , Fattah Rasem , Bugge Thomas H. , Leppla Stephen H. , Liu Shihui
Published: November 2015

Anthrax lethal toxin (LT) is an A-B type toxin secreted by Bacillus anthracis, consisting of the cellular binding moiety, protective antigen (PA) and the catalytic moiety, lethal factor (LF). To target cells, PA binds to cell-surface receptors and is then proteolytically processed forming a LF-binding competent PA oligomer where each LF binding site is comprised of three subsites on two adjacent PA monomers. We previously generated PA-U2-R200A, a urokinase-activated PA variant with LF-binding subsite II residue Arg200 mutated to Ala and PA-L1-I210A, a matrix metalloproteinase-activated PA variant with subsite III residue Ile210 mutated to Ala. PA-U2-R200A and PA-L1-I210A displayed reduced cytotoxicity when used singly. However, when combined, they formed LF-binding competent heterogeneous oligomers by intermolecular complementation and achieved high specificity in tumor targeting. Nevertheless, each of these proteins, in particular PA-L1-I210A, retained residual LF-binding ability. In this work, we screened a library containing all possible amino acid substitutions for LF-binding site to find variants with activity strictly dependent upon intermolecular complementation. PA-I207R was identified as an excellent replacement for the original clockwise-side variant, PA-I210A. Consequently, the new combination of PA-L1-I207R and PA-U2-R200A showed potent anti-tumor activity and low toxicity, exceeding the performance of the original combination and warranting further investigation.
Compact component for integrated quantum optic processing
Authors: Sahu Partha Pratim
Published: November 2015

Quantum interference is indispensable to derive integrated quantum optic technologies (1–2). For further progress in large scale integration of quantum optic circuit, we have introduced first time two mode interference (TMI) coupler as an ultra compact component. The quantum interference varying with coupling length corresponding to the coupling ratio is studied and the larger HOM dip with peak visibility ~0.963 ± 0.009 is found at half coupling length of TMI coupler. Our results also demonstrate complex quantum interference with high fabrication tolerance and quantum visibility in TMI coupler.
Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy
Authors: Chen Jieliang , Wu Min , Wang Fan , Zhang Wen , Wang Wei , Zhang Xiaonan , Zhang Jiming , Liu Yinghui , Liu Yi , Feng Yanling , Zheng Ye , Hu Yunwen , Yuan Zhenghong
Published: November 2015

During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense.
Atomically Sharp Interface in an h-BN-epitaxial graphene van der Waals Heterostructure
Authors: Sediri Haikel , Pierucci Debora , Hajlaoui Mahdi , Henck Hugo , Patriarche Gilles , Dappe Yannick J. , Yuan Sheng , Toury Bérangère , Belkhou Rachid , Silly Mathieu G. , Sirotti Fausto , Boutchich Mohamed , Ouerghi Abdelkarim
Published: November 2015

Stacking various two-dimensional atomic crystals is a feasible approach to creating unique multilayered van der Waals heterostructures with tailored properties. Herein for the first time, we present a controlled preparation of large-area h-BN/graphene heterostructures via a simple chemical deposition of h-BN layers on epitaxial graphene/SiC(0001). Van der Waals forces, which are responsible for the cohesion of the multilayer system, give rise to an abrupt interface without interdiffusion between graphene and h-BN, as shown by X-ray Photoemission Spectroscopy (XPS) and direct observation using scanning and High-Resolution Transmission Electron Microscopy (STEM/HRTEM). The electronic properties of graphene, such as the Dirac cone, remain intact and no significant charge transfer i.e. doping, is observed. These results are supported by Density Functional Theory (DFT) calculations. We demonstrate that the h-BN capped graphene allows the fabrication of vdW heterostructures without altering the electronic properties of graphene.
Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy
Authors: Yuan Zhengrong , Li Jiao , Hu Ruiqi , Jiao Yang , Han Yingying , Weng Qiang
Published: November 2015

Published data have shown inconsistent results about the pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. This meta-analysis aimed to summarize published findings and provide more reliable association. A total of 53 eligible studies including 7433 patients were included. Patients bearing the favorable TrpTrp and TrpArg genotypes of Arg194Trp were more likely to better response rates to platinum-based chemotherapy compared to those with the unfavorable ArgArg genotype (TrpTrp+TrpArg vs. ArgArg: odds ratio (OR) = 2.02, 95% CI, 1.66–2.45). The GlnGln and GlnArg genotypes of Arg399Gln were significantly associated with the poorer response rates compared to those with the ArgArg genotype (GlnGln +GlnArg vs. ArgArg: OR = 0.68, 95% CI, 0.54–0.86). The GlnGln genotype might be more closely associated with shorter survival time and higher risks of death for patients (GlnGln vs. ArgArg: hazard ratio (HR) = 1.14, 95% CI, 0.75–1.75). Our cumulative meta-analyses indicated a distinct apparent trend toward a better response rate for Arg194Trp, but a poorer response rate in Arg399Gln. These findings indicate a predictive role of XRCC1 polymorphisms in clinical outcomes. The use of XRCC1 polymorphisms as predictive factor of clinical outcomes in personalized chemotherapy treatment requires further verification from large well-designed pharmacogenetics studies.
Detection of Infertility-related Neutralizing Antibodies with a Cell-free Microfluidic Method
Authors: Eyer Klaus , Root Katharina , Verboket Pascal E. , Dittrich Petra S.
Published: November 2015

The unwanted emergence of neutralizing antibodies (nAbs) against an endogenous or a therapeutic protein can result in deficiency diseases or therapy failure. Here, we developed a cell-free microfluidic method for the sensitive detection and quantification of nAbs in human serum that are associated with infertility. We used cell-derived vesicles containing the luteinizing hormone (LH)/choriogonadotropin receptor (LHHCGR) to detect nAbs against LH. The method exploits the entire cellular signal amplification mechanism and facilitates the detection of as little as 0.44 nM of LH-nAb (Kd 1.5 nM) in human serum matrix within only 15 minutes. In addition, dose-response curves can be generated in less than 2 hours to evaluate the nAB concentration and dissociation constant. The developed system is devoid of problems associated with cell-based assays and we believe that this simple effect-directed analysis can be used in clinical environments and is adaptable to other hormones or cytokines and their respective nAbs.
Transcriptional analysis of micronutrient zinc-associated response for enhanced carbohydrate utilization and earlier solventogenesis in Clostridium acetobutylicum
Authors: Wu You-Duo , Xue Chuang , Chen Li-Jie , Wan Hui-Hui , Bai Feng-Wu
Published: November 2015

The micronutrient zinc plays vital roles in ABE fermentation byClostridium acetobutylicum. In order to elucidate the zinc-associated response for enhanced glucose utilization and earlier solventogenesis, transcriptional analysis was performed on cells grown in glucose medium at the exponential growth phase of 16 h without/with supplementary zinc. Correspondingly, the geneglcG(CAC0570) encoding a glucose-specific PTS was significantly upregulated accompanied with the other two genes CAC1353 and CAC1354 for glucose transport in the presence of zinc. Additionally, genes involved in the metabolisms of six other carbohydrates (maltose, cellobiose, fructose, mannose, xylose and arabinose) were differentially expressed, indicating that the regulatory effect of micronutrient zinc is carbohydrate-specific with respects to the improved/inhibited carbohydrate utilization. More importantly, multiple genes responsible for glycolysis (glcKandpykA), acidogenesis (thlA, crt, etfA, etfBandbcd) and solventogenesis (ctfBandbdhA) ofC. acetobutylicumprominently responded to the supplementary zinc at differential expression levels. Comparative analysis of intracellular metabolites revealed that the branch node intermediates such as acetyl-CoA, acetoacetyl-CoA, butyl-CoA and reducing power NADH remained relatively lower whereas more ATP was generated due to enhanced glycolysis pathway and earlier initiation of solventogenesis, suggesting that the micronutrient zinc-associated response for the selected intracellular metabolisms is significantly pleiotropic.
The human decapping scavenger enzyme DcpS modulates microRNA turnover
Authors: Meziane Oussama , Piquet Sandra , Bossé Gabriel D. , Gagné Dominic , Paquet Eric , Robert Claude , Tones Michael A. , Simard Martin J.
Published: November 2015

The decapping scavenger enzyme DcpS is known for its role in hydrolyzing the cap structure following mRNA degradation. Recently, we discovered a new function in miRNA degradation activation for the ortholog of DcpS in C. elegans. Here we show that human DcpS conserves its role in miRNA turnover. In human cells, DcpS is a nucleocytoplasmic shuttling protein that activates miRNA degradation independently of its scavenger decapping activity in the cytoplasmic compartment. We also demonstrate that this new function for DcpS requires the contribution of the 5′-3′ exonuclease Xrn2. Our findings support a conserved role of DcpS as a modulator of miRNA turnover in animals.
A new cost-effective method to mitigate ammonia loss from intensive cattle feedlots: application of lignite
Authors: Chen Deli , Sun Jianlei , Bai Mei , Dassanayake Kithsiri B. , Denmead Owen T. , Hill Julian
Published: November 2015

In open beef feedlot systems, more than 50% of dietary nitrogen (N) is lost as ammonia (NH3). Here we report an effective and economically-viable method to mitigate NH3 emissions by the application of lignite. We constructed two cattle pens (20 × 20 m) to determine the effectiveness of lignite in reducing NH3 emissions. Twenty-four steers were fed identical commercial rations in each pen. The treatment pen surface was dressed with 4.5 kg m−2 lignite dry mass while no lignite was applied in the control pen. We measured volatilised NH3 concentrations using Ecotech EC9842 NH3 analysers in conjunction with a mass balance method to calculate NH3 fluxes. Application of lignite decreased NH3 loss from the pen by approximately 66%. The cumulative NH3 losses were 6.26 and 2.13 kg N head−1 in the control and lignite treatment, respectively. In addition to the environmental benefits of reduced NH3 losses, the value of retained N nutrient in the lignite treated manure is more than $37 AUD head−1 yr−1, based on the current fertiliser cost and estimated cost of lignite application. We show that lignite application is a cost-effective method to reduce NH3 loss from cattle feedlots.
Synthesis of Extended Atomically Perfect Zigzag Graphene - Boron Nitride Interfaces
Authors: Drost Robert , Kezilebieke Shawulienu , M. Ervasti Mikko , Hämäläinen Sampsa K. , Schulz Fabian , Harju Ari , Liljeroth Peter
Published: November 2015

The combination of several materials into heterostructures is a powerful method for controlling material properties. The integration of graphene (G) with hexagonal boron nitride (BN) in particular has been heralded as a way to engineer the graphene band structure and implement spin- and valleytronics in 2D materials. Despite recent efforts, fabrication methods for well-defined G-BN structures on a large scale are still lacking. We report on a new method for producing atomically well-defined G-BN structures on an unprecedented length scale by exploiting the interaction of G and BN edges with a Ni(111) surface as well as each other.
Multidrug resistance protein 1 reduces the aggregation of mutant huntingtin in neuronal cells derived from the Huntington’s disease R6/2 model
Authors: Im Wooseok , Ban Jae-Jun , Chung Jin-Young , Lee Soon-Tae , Chu Kon , Kim Manho
Published: November 2015

Mutant huntingtin (mHtt) aggregation in the nucleus is the most readily apparent phenotype and cause of neuronal death in Huntington’s disease (HD). Inhibiting mHtt aggregation reduces cell death in the brain and is thus a promising therapeutic approach. The results of the present study demonstrated that mHtt aggregation in the nucleus was altered by the activity of multidrug resistance protein 1 (MDR1), which was experimentally modulated by verapamil, siRNA and an expression vector. MDR1 detoxifies drugs and metabolites through its excretory functions in the membrane compartment, thereby protecting cells against death or senescence. When they were treated with verapamil, R6/2 mice showed a progressive decline in rotarod performance and increased mHtt aggregation in the brain. Using neuronal stem cells from R6/2 mice, we developed an in vitro HD model to test mHtt accumulation in the nuclei of neurons. When MDR1 activity in cells was decreased by verapamil or siRNA, mHtt aggregation in the nuclei increased, whereas the induction of MDR1 resulted in a decrease in mHtt aggregation. Thus, our data provide evidence that MDR1 plays an important role in the clearance of mHtt aggregation and may thus be a potential target for improving the survival of neurons in Huntington’s disease.
First-principles study of the effect of functional groups on polyaniline backbone
Authors: Chen X. P. , Jiang J. K. , Liang Q. H. , Yang N. , Ye H. Y. , Cai M. , Shen L. , Yang D. G. , Ren T. L.
Published: November 2015

We present a first-principles density functional theory study focused on how the chemical and electronic properties of polyaniline are adjusted by introducing suitable substituents on a polymer backbone. Analyses of the obtained energy barriers, reaction energies and minimum energy paths indicate that the chemical reactivity of the polyaniline derivatives is significantly enhanced by protonic acid doping of the substituted materials. Further study of the density of states at the Fermi level, band gap, HOMO and LUMO shows that both the unprotonated and protonated states of these polyanilines are altered to different degrees depending on the functional group. We also note that changes in both the chemical and electronic properties are very sensitive to the polarity and size of the functional group. It is worth noting that these changes do not substantially alter the inherent chemical and electronic properties of polyaniline. Our results demonstrate that introducing different functional groups on a polymer backbone is an effective approach to obtain tailored conductive polymers with desirable properties while retaining their intrinsic properties, such as conductivity.
Establishment and Characterization of Human Germline Stem Cell Line with Unlimited Proliferation Potentials and no Tumor Formation
Authors: Hou Jingmei , Niu Minghui , Liu Linhong , Zhu Zijue , Wang Xiaobo , Sun Min , Yuan Qingqing , Yang Shi , Zeng Wenxian , Liu Yang , Li Zheng , He Zuping
Published: November 2015

Spermatogonial stem cells (SSCs) have significant applications in both reproductive and regenerative medicine. However, primary human SSCs are very rare and a human SSC line has not yet been available. In this study, we have for the first time reported a stable human SSC line by stably expressing human SV40 large T antigen. RT-PCR, immunocytochemistry and Western blots revealed that this cell line was positive for a number of human spermatogonial and SSC hallmarks, including VASA, DAZL, MAGEA4, GFRA1, RET, UCHL1, GPR125, PLZF and THY1, suggesting that these cells are human SSCs phenotypically. Proliferation analysis showed that the cell line could be expanded with significant increases of cells for 1.5 years and high levels of PCNA, UCHL1 and SV40 were maintained for long-term culture. Transplantation assay indicated that human SSC line was able to colonize and proliferatein vivoin the recipient mice. Neither Y chromosome microdeletions of numerous genes nor tumor formation was observed in human SSC line although there was abnormal karyotype in this cell line. Collectively, we have established a human SSC line with unlimited proliferation potentials and no tumorgenesis, which could provide an abundant source of human SSCs for their mechanistic studies and translational medicine.
A Wireless Intracranial Brain Deformation Sensing System for Blast-Induced Traumatic Brain Injury
Authors: Song S. , Race N. S. , Kim A. , Zhang T. , Shi R. , Ziaie B.
Published: November 2015

Blast-induced traumatic brain injury (bTBI) has been linked to a multitude of delayed-onset neurodegenerative and neuropsychiatric disorders, but complete understanding of their pathogenesis remains elusive. To develop mechanistic relationships between bTBI and post-blast neurological sequelae, it is imperative to characterize the initiating traumatic mechanical events leading to eventual alterations of cell, tissue and organ structure and function. This paper presents a wireless sensing system capable of monitoring the intracranial brain deformation in real-time during the event of a bTBI. The system consists of an implantable soft magnet and an external head-mounted magnetic sensor that is able to measure the field in three dimensions. The change in the relative position of the soft magnet WITH respect to the external sensor as the result of the blast wave induces changes in the magnetic field. The magnetic field data in turn is used to extract the temporal and spatial motion of the brain under the blast wave in real-time. The system has temporal and spatial resolutions of 5 μs and 10 μm. Following the characterization and validation of the sensor system, we measured brain deformations in a live rodent during a bTBI.
Quantum secret sharing via local operations and classical communication
Authors: Yang Ying-Hui , Gao Fei , Wu Xia , Qin Su-Juan , Zuo Hui-Juan , Wen Qiao-Yan
Published: November 2015

We investigate the distinguishability of orthogonal multipartite entangled states in d-qudit system by restricted local operations and classical communication. According to these properties, we propose a standard (2, n)-threshold quantum secret sharing scheme (called LOCC-QSS scheme), which solves the open question in [Rahaman et al., Phys. Rev. A, 91, 022330 (2015)]. On the other hand, we find that all the existing (k, n)-threshold LOCC-QSS schemes are imperfect (or “ramp”), i.e., unauthorized groups can obtain some information about the shared secret. Furthermore, we present a (3, 4)-threshold LOCC-QSS scheme which is close to perfect.
Non-cultured dermal-derived mesenchymal cells attenuate sepsis induced by cecal ligation and puncture in mice
Authors: Wang Yu , Tan Li , Jin Jie , Sun Huiqin , Chen Zelin , Tan Xu , Su Yongping , Shi Chunmeng
Published: November 2015

Sepsis remains a threat to critically ill patients and carries a high morbidity and mortality. Cell–based therapies have risen in prominence in recent years. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we described for the first time the use of non-cultured DMCs for treating sepsis in a cecal ligation and puncture (CLP) mouse model and investigated their immunomodulatory effects. We found that non-cultured DMCs administration provides a beneficial effect to improve survival in CLP-induced sepsis. This effect is partly mediated by the ability of DMCs to home to sites of injury, to reduce the inflammatory response, to inhibit apoptosis and to stimulate macrophage migration and phagocytosis. Our further findings suggest that DMCs treatment modulates the beneficial cytoprotective effects exhibited during sepsis, at least in part, by altering miRNA expression. These discoveries provide important evidence that non-cultured DMCs therapy has a specific anti-inflammatory effect on sepsis and provide the basis for the development of a new therapeutic strategy for managing clinical sepsis.
Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum
Authors: Tian Xinhui , Yue Rongcai , Zeng Huawu , Li Honglin , Shan Lei , He Weiwei , Shen Yunheng , Zhang Weidong
Published: November 2015

Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)−1 and (−)−1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)−1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (−)−1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)−1 and (−)−1.
Long-distance quantum information transfer with strong coupling hybrid solid system
Authors: Zhang Feng-Yang , Chen Xin-Yu , Li Chong , Song He-Shan
Published: November 2015

In this paper, we demonstrate how information can be transferred among the long-distance memory units in a hybrid solid architecture, which consists the nitrogen-vacancy (NV) ensemble acting as the memory unit, the LC circuit acting as the transmitter (receiver) and the flux qubit acting as the interface. Numerical simulation demonstrates that the high-fidelity quantum information transfer between memory unit and transmitter (receiver) can be implemented and this process is robust to both the LC circuit decay and NV ensemble spontaneous emission.
Majorana zero modes in the hopping-modulated one-dimensional p-wave superconducting model
Authors: Gao Yi , Zhou Tao , Huang Huaixiang , Huang Ran
Published: November 2015

We investigate the one-dimensional p-wave superconducting model with periodically modulated hopping and show that under time-reversal symmetry, the number of the Majorana zero modes (MZMs) strongly depends on the modulation period. If the modulation period is odd, there can be at most one MZM. However if the period is even, the number of the MZMs can be zero, one and two. In addition, the MZMs will disappear as the chemical potential varies. We derive the condition for the existence of the MZMs and show that the topological properties in this model are dramatically different from the one with periodically modulated potential.
Proteomic analysis of tylosin-resistant Mycoplasma gallisepticum reveals enzymatic activities associated with resistance
Authors: Xia Xi , Wu Congming , Cui Yaowen , Kang Mengjiao , Li Xiaowei , Ding Shuangyang , Shen Jianzhong
Published: November 2015

Mycoplasma gallisepticum is a significant pathogenic bacterium that infects poultry, causing chronic respiratory disease and sinusitis in chickens and turkeys, respectively. M. gallisepticum infection poses a substantial economic threat to the poultry industry and this threat is made worse by the emergence of antibiotic-resistant strains. The mechanisms of resistance are often difficult to determine; for example, little is known about antibiotic resistance of M. gallisepticum at the proteome level. In this study, we performed comparative proteomic analyses of an antibiotic (tylosin)-resistant M. gallisepticum mutant and a susceptible parent strain using a combination of two-dimensional differential gel electrophoresis and nano-liquid chromatography-quadrupole-time of flight mass spectrometry. Thirteen proteins were identified as differentially expressed in the resistant strain compared to the susceptible strain. Most of these proteins were related to catalytic activity, including catalysis that promotes the formylation of initiator tRNA and energy production. Elongation factors Tu and G were over-expressed in the resistant strains and this could promote the binding of tRNA to ribosomes and catalyze ribosomal translocation, the coordinated movement of tRNA and conformational changes in the ribosome. Taken together, our results indicate that M. gallisepticum develops resistance to tylosin by regulating associated enzymatic activities.
Conversion of Biomass into Sugars
Authors: Bhaumik Prasenjit , Dhepe Paresh Laxmikant
Published: November 2015

The synthesis of sugars from disaccharides and polysaccharides sourced from lignocellulosic biomass (agricultural waste, forest residues) is at the onset in the bio-refinery concept. This chapter presents a comprehensive overview of multiple strategies researched from the early 1990s to design and develop various catalysts and catalytic processes to hydrolyse saccharides (cellulose, hemicelluloses) into sugars by both academia and industry. A large body of work is done with mineral acids and enzyme catalysed processes, which are also practiced on an industrial scale. The effects of pH, time, temperature, concentration, substrate type etc. are studied and discussions are focused on those in the chapter along with discussions on kinetics and mechanisms. Recent developments on heterogeneous catalysts (solid acids, supported metals) are also discussed in the chapter. The pros and cons of using isolated saccharides and lignocellulose embedded saccharides as substrates are discussed. An outline of the future path for research in this area is presented for the benefit of researchers.
Recent Advances in the Synthesis of Sugar-based Surfactants
Authors: Kovensky José , Grand Eric
Published: November 2015

New challenges have to be faced in the field of surfactants. Green processes and products are increasingly demanded: green syntheses, natural building blocks as starting materials, products of high biodegradability and devoid of toxicity, low costs. Sugar-based surfactants successfully fit all these requirements and thus they are at the centre of the research of new green surfactants with specific properties. Most of the syntheses published in the literature from 2008 to 2014 are about new structures presenting variations on the sugar moiety, the hydrophobic chain, and the introduction of spacer arms between the polar head and the lipophilic tail. Carbohydrates offer a wide diversity of monomers and dimers that can be cyclic (furanose, pyranose) or acyclic to be used as a polar head. Among all the available hydroxyl groups of a sugar unit, two are particularly suitable for substitution: primary alcohols and the hydroxyl at the anomeric position. The hydrophobic chain can be more complex than the classical alkyl chain, as chemists are looking for new properties that can be brought by the use of fluoroalkyl chains or polysiloxanes. This chapter reviews recent bibliography and reports (patents excluded) on the synthesis of sugar-based surfactants, including chemical and chemoenzymatic methods.
Oligosaccharides for Pharmaceutical Applications
Authors: Rahkila Jani , Saloranta Tiina , Leino Reko
Published: November 2015

Carbohydrates, being the most abundant class of biopolymers on earth, have, due to their structural diversity and inherent chirality, been subject to comprehensive biological investigations. Their biological importance is unquestionable, as a wide range of biological recognition and communication phenomena depend on complex oligo- and polysaccharide structures. This also makes carbohydrates attractive targets for developing new pharmaceuticals. In this chapter, a fundamental overview of the synthesis of oligosaccharides from the viewpoint of both traditional synthetic methods as well as fully automated methodologies is provided. Furthermore, selected commercially available oligosaccharide pharmaceuticals as well as promising new compounds under development are briefly discussed.
Characteristics of the Underwater Light Field
Authors: Loiselle Steven A. , Duan Hongtao , Cao Zhigang
Published: November 2015

Photochemical processes are controlled by the characteristics of the underwater light field. These conditions will change over time and space, in relation to the position, concentration and properties of the optically active components in the water column as well as the direction and intensity of the incident solar radiation. This chapter will examine the underwater light field, the spectral properties of those components that influence this field and their estimation using appropriate modelling approaches as well as in situ and remote technologies.
Direct Photolysis Processes
Authors: Richard Claire , Hoffmann Norbert
Published: November 2015

Solar light is able to photoinduce the phototransformation of a lot of pesticides. In this chapter, we describe some of the most important photochemical processes leading to the chemical transformation of pesticides, in particular photodehalogenation, photoisomerization, photo-Fries and photo-Claisen. In each case, theoretical considerations are given and illustrated by examples taken from the literature. This chapter provides useful data for the understanding of the photoreactivity of a wide range of molecules of environmental concern.
Photochemical Reaction Kinetics in Surface Waters
Authors: Vione Davide
Published: November 2015

The photochemical transformation kinetics of xenobiotics in surface waters can be modelled, based on a number of photochemically significant parameters of the xenobiotic (absorption spectrum, direct photolysis quantum yield, second-order reaction rate constants with •OH, CO3−•, 1O2 and 3CDOM*) and on some environmental variables (water depth, dissolved organic carbon (DOC), concentration values of nitrate, nitrite, carbonate and bicarbonate). The latter define the ability of the water body to attenuate sunlight in the water column and/or to photochemically produce reactive transient species, while the photochemical parameters of the xenobiotic measure its ability to react via the different photochemical reaction pathways. All of the above calculations can be carried out using the APEX software (Aqueous Photochemistry of Environmentally-occurring Xenobiotics). The software is also able to predict the seasonal trends of the phototransformation kinetics and to assess the uncertainty of the model output.
Photochemical Fate of Micropollutants in Aqueous Systems Through Field Studies and Laboratory Simulation
Authors: Calza Paola , Fabbri Debora
Published: November 2015

This chapter will give insight into the techniques that can be used to assess the transformation (including the phototransformation) of pollutants in environmental waters. It will also include the laboratory experiments that are more useful to simulate the abiotic transformation of pollutants occurring in the euphotic zone and leading to potentially harmful transformation products. Particular attention will be paid to the quantitative structure activity relationship (QSAR) modelling process, to the photocatalytic process and to the approach utilized in the identification of the unknown transformation products.
Models for Nonspecific Binding and Partitioning
Authors: Korzekwa Ken
Published: November 2015

Nonspecific binding or partitioning plays a major role in the distribution and disposition of drugs. Plasma protein binding and partitioning into tissue membranes are two important processes that influence unbound drug concentrations and therefore most pharmacological and toxicological properties. Multiple binding proteins and multiple binding sites on these proteins complicate models for plasma protein binding. Computational models for plasma protein binding can generally explain ∼70% of the variance for diverse datasets. Nonspecific binding processes are important when scaling up microsomal or cellular data to predict clearance and drug interactions, and models for microsomal membrane binding and nonspecific binding to hepatocytes are available. Distribution into cells and organelles due to pH differences can be readily modeled by pH partitioning equations. Models for the volume of distribution include descriptor-based models and mechanistic models. Within the physiologically based pharmacokinetic framework there are integrated models to predict volume of distribution that incorporate plasma protein binding, lipid partitioning, and pH partitioning. However, the current implementations of these models require some experimental data.
Metabolite Profiling
Authors: Schmidt James M.
Published: November 2015

Understanding the metabolism of a compound by identifying which metabolites are formed during in vitro or in vivo studies—that is, “metabolite profiling”—is a critical part of the drug discovery and development process, from assisting in lead optimization to better understanding the pharmacology, pharmacokinetics, and toxicology of drug candidates. Regulatory authorities encourage the identification of differences in drug metabolism between and among preclinical animal species as early as possible during the drug development process; indeed, the discovery of a disproportionate, pharmacologically active, and/or toxic drug metabolite late in drug development can cause delays in development, approval, and marketing. Metabolite profiling is at an interesting interdisciplinary intersection with organic synthesis, experimental biology, bio-analytical chemistry, informatics, toxicology, intellectual property, regulatory science, business considerations, and more. The present chapter provides an overview of the rationale for metabolite profiling, with attention given to special aspects such as in silico metabolite prediction, quantitation of unknown metabolites, metabolite synthesis, profiling of enantioselective metabolite pathways, the future of metabolite profiling, and more.
Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs
Authors: Wolf C. Roland , Kapelyukh Yury , Scheer Nico , Henderson Colin J.
Published: November 2015

The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.
Chemically Reactive Versus Stable Drug Metabolites: Role in Adverse Drug Reactions
Authors: Baillie Thomas A.
Published: November 2015

It has been appreciated for some time that drug metabolites may contribute to both the beneficial and adverse properties of therapeutic agents, although the underlying mechanisms of metabolite-induced toxicities have not always been clear. Studies over the past 40 years on the relationship between biotransformation and drug toxicity have implicated chemically reactive metabolites as mediators of many serious drug toxicities, whereas few examples exist where stable metabolites whose structures do not differ greatly from those of their respective parents appear to be involved. As a result, screens for metabolic activation are now incorporated routinely into lead optimization programs with the goal of providing rational approaches for the structural redesign of lead compounds to eliminate, or at least minimize, the propensity for reactive metabolite formation. In this chapter, specific examples are given of drug discovery programs that have benefited from this approach, and contemporary approaches to address regulatory guidance on stable Metabolites in Safety Testing (“MIST”) are discussed. Finally, some future directions in this field are highlighted stemming from rapid technical developments in bioanalysis, bioinformatics, genetics, in vitro and in vivo animal models, and in silico tools to both understand and predict the roles of drug metabolites in adverse drug reactions.
Drug–Drug Interactions: Regulatory and Theoretical Considerations, and an Industry Perspective
Authors: Tang Cuyue , Hochman Jerome , Prueksaritanont Thomayant
Published: November 2015

In this review, a number of theoretical bases and regulatory framework are presented for drug–drug interactions (DDIs), with emphasis on those related to absorption and distribution. Also presented is an industry perspective on how to approach these issues in support of drug development. Overall, holistic integration and understanding of the pharmaceutical (e.g., pH-dependent solubility) and pharmacological (e.g., gastrointestinal physiology and therapeutic margin) profiles, as well as pharmacokinetics and underlying absorption and disposition determinants (e.g., clearance, volume of distribution, permeability and protein binding) of drug candidates in various clinical setting should be considered as this can be valuable in ensuring the safe and effective use of new drugs.
Induction of Hepatic Cytochrome P450 Enzymes: Importance in Drug Development and Toxicity
Authors: Lake Brian G. , Price Roger J.
Published: November 2015

Throughout evolution mammals have developed a series of enzyme systems to detoxify xenobiotics (also termed foreign compounds) and hence promote their excretion from the body. The liver is the major site of xenobiotic metabolism in mammals of which the most important enzyme system is the cytochrome P450 (CYP) superfamily, which catalyses the oxygenation of a multitude of xenobiotics. Human, rat and mouse liver contain CYP enzymes in various subfamilies including CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, CYP3A and CYP4A enzymes. The activities of many human and rodent hepatic CYP enzymes can be induced by a range of xenobiotics, although marked species differences are known to exist. Hepatic CYP enzyme induction normally occurs by receptor mediated mechanisms leading to an increase in gene transcription. In humans, the consequences of induction of CYP enzymes may result in clinically important drug–drug interactions, including organ transplant rejection, diminished antiretroviral effect, reduced anticoagulant effect and unplanned pregnancies. The induction of hepatic CYP enzymes by nongenotoxic agents in rodents may also be associated with tumour formation in the liver and other tissues (e.g. thyroid gland). Such effects in rodents are due to the mitogenic properties of the CYP enzyme inducers and are not relevant for humans.