bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory and Antitumor Effects of a Novel TLR7 Agonist Combined with Lapatinib
Authors: Gao Ningning , Zhong Jingjing , Wang Xiaodong , Jin Zhenchao , Li Wang , Liu Yu , Diao Yuwen , Wang Zhulin , Jiang Wenqi , Jin Guangyi 
Published: December 2016

AbstractAs new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance. We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo, without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).
Illegitimate translation causes unexpected gene expression from on-target out-of-frame alleles created by CRISPR-Cas9
Authors: Makino Shigeru , Fukumura Ryutaro , Gondo Yoichi 
Published: December 2016

AbstractCRISPR-Cas9 is efficient enough to knock out both alleles directly by introducing out-of-frame mutations. We succeeded in making biallelic on-target frameshift mutations of the endogenous Gli3 gene; however, the GLI3 protein was expressed in all six of the established cell lines carrying homozygous out-of-frame mutations. We developed a dual-tagged expression vector and proved that illegitimate translation (ITL) was the cause of the unexpected Gli3 expression. Thus, gene expression must be examined even if designed on-target out-of-frame sequences are introduced by genome editing. In addition, it is highly recommended to pre-examine the occurrence of ITL in vitro prior to the design and construction of any genome-editing vectors. In vitro assay systems such as the dual-tagged ITL assay system developed in this study should aid the identification and elucidation of ITL-based human diseases and gene expression.
In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells
Authors: He Yun , Wang Lidai , Shi Junhui , Yao Junjie , Li Lei , Zhang Ruiying , Huang Chih-Hsien , Zou Jun , Wang Lihong V. 
Published: December 2016

AbstractMetastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature.
A diketopiperazine factor from Rheinheimera aquimaris QSI02 exhibits anti-quorum sensing activity
Authors: Sun Shiwei , Dai Xiaoyun , Sun Jiao , Bu Xiangguo , Weng Caihong , Li Hui , Zhu Hu 
Published: December 2016

AbstractAn ethyl acetate (EtOAc) extract isolated from the marine bacterium, Rheinheimera aquimaris QSI02, was found to exhibit anti-quorum sensing (anti-QS) activity. A subsequent bioassay-guided isolation protocol led to the detection of an active diketopiperazine factor, cyclo(Trp-Ser). Biosensor assay data showed that the minimum inhibitory concentration (MIC) of cyclo(Trp-Ser) ranged from 3.2 mg/ml to 6.4 mg/m for several microorganisms, including Escherichia coli, Chromobacterium violaceum CV026, Pseudomonas aeruginosa PA01, Staphylococcus aureus, and Candida albicans. Additionally, sub-MICs of cyclo(Trp-Ser) decreased the QS-regulated violacein production in C. violaceum CV026 by 67%. Furthermore, cyclo(Trp-Ser) can decrease QS-regulated pyocyanin production, elastase activity and biofilm formation in P. aeruginosa PA01 by 65%, 40% and 59.9%, respectively. Molecular docking results revealed that cyclo(Trp-Ser) binds to CviR receptor more rigidly than C6HSL with lower docking energy −8.68 kcal/mol, while with higher binding energy of −8.40 kcal/mol than 3-oxo-C12HSL in LasR receptor. Molecular dynamics simulation suggested that cyclo(Trp-Ser) is more easy to bind to CviR receptor than natural signaling molecule, but opposite in LasR receptor. These results suggest that cyclo(Trp-Ser) can be used as a potential inhibitor to control QS systems of C. violaceum and P. aeruginosa and provide increased the understanding of molecular mechanism that influences QS-regulated behaviors.
Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma
Authors: Horst K. , Simon T. P. , Pfeifer R. , Teuben M. , Almahmoud K. , Zhi Q. , Santos S. Aguiar , Wembers C. Castelar , Leonhardt S. , Heussen N. , Störmann P. , Auner B. , Relja B. , Marzi I. , Haug A. T. , van Griensven M. , Kalbitz M. , Huber-Lang M. , Tolba R. , Reiss L. K. , Uhlig S. , Marx G. , Pape H. C. , Hildebrand F. 
Published: December 2016

AbstractChest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.
Knowledge-Guided Bioinformatics Model for Identifying Autism Spectrum Disorder Diagnostic MicroRNA Biomarkers
Authors: Shen Li , Lin Yuxin , Sun Zhandong , Yuan Xuye , Chen Luonan , Shen Bairong 
Published: December 2016

AbstractAutism spectrum disorder (ASD) is a severe neurodevelopmental disease with a high incidence and effective biomarkers are urgently needed for its diagnosis. A few previous studies have reported the detection of miRNA biomarkers for autism diagnosis, especially those based on bioinformatics approaches. In this study, we developed a knowledge-guided bioinformatics model for identifying autism miRNA biomarkers. We downloaded gene expression microarray data from the GEO Database and extracted genes with expression levels that differed in ASD and the controls. We then constructed an autism-specific miRNA–mRNA network and inferred candidate autism biomarker miRNAs based on their regulatory modes and functions. We defined a novel parameter called the autism gene percentage as autism-specific knowledge to further facilitate the identification of autism-specific biomarker miRNAs. Finally, 11 miRNAs were screened as putative autism biomarkers, where eight miRNAs (72.7%) were significantly dysregulated in ASD samples according to previous reports. Functional enrichment results indicated that the targets of the identified miRNAs were enriched in autism-associated pathways, such as Wnt signaling (in KEGG and IPA), cell cycle (in KEGG), and glioblastoma multiforme signaling (in IPA), thereby supporting the predictive power of our model.
One-pot synthesis of carbon supported calcined-Mg/Al layered double hydroxides for antibiotic removal by slow pyrolysis of biomass waste
Authors: Tan Xiaofei , Liu Shaobo , Liu Yunguo , Gu Yanling , Zeng Guangming , Cai Xiaoxi , Yan ZhiLi , Yang Chunping , Hu Xinjiang , Chen Bo 
Published: December 2016

AbstractA biochar supported calcined-Mg/Al layered double hydroxides composite (CLDHs/BC) was synthesized by a one-pot slow pyrolysis of LDHs preloaded bagasse biomass. Multiple characterizations of the product illustrated that the calcined-Mg/Al layered double hydroxides (CLDHs) were successfully coated onto the biochar in slow pyrolysis of pre-treated biomass. The as-synthesized CLDHs/BC could efficiently remove antibiotic tetracycline from aqueous solutions. The coating of CLDHs significantly increased the adsorption ability of biochar, and CLDHs/BC exhibited more than 2 times higher adsorption capacity than that of the pristine biochar (BC) in the tested pH range. The maximum adsorption capacity of CLDHs/BC for tetracycline was 1118.12 mg/g at 318 K. The experimental results suggested that the interaction with LDHs on biochar played a dominant role in tetracycline adsorption, accompanied with π–π interaction and hydrogen bond. This study provides a feasible and simple approach for the preparation of high-performance material for antibiotics contaminated wastewater treatment in a cost-effective way.
BACH1 Promotes Temozolomide Resistance in Glioblastoma through Antagonizing the Function of p53
Authors: Nie Er , Jin Xin , Wu Weining , Yu Tianfu , Zhou Xu , Zhi Tongle , Shi Zhumei , Zhang Junxia , Liu Ning , You Yongping 
Published: December 2016

AbstractThe acquisition of drug resistance is a persistent clinical problem limiting the successful treatment of glioblastoma (GBM). However, the molecular mechanisms by which initially chemoresponsive tumors develop therapeutic resistance remain poorly understood. In this study, we report that BACH1, a heme-binding protein that participates in transcriptional repression or activation, was significantly upregulated in glioblastoma tissues. Overexpression of BACH1 in GBM cells conferred resistance to temozolomide, whereas its inhibition markedly sensitized resistant cells to temozolomide in vitro and in vivo. Further investigation revealed that BACH1 activation significantly enhanced the expression of MGMT, and depletion of p53 disrupted the effects of BACH1 on MGMT and temozolomide resistance. P53 sequesters SP1 to prevent its binding to the MGMT promoter region and thus inhibits MGMT expression. Moreover, BACH1 overexpression impaired the association between p53 and SP1 via competitive binding p53, and antagonized the impact of p53 on MGMT expression. Finally, we found that BACH1 low expression correlated with better prognosis in GBM patients undergoing temozolomide therapy, especially in patients with wild-type TP53. Collectively, our findings identify a potential mechanism by which wild-type TP53 GBM cells develop resistance to temozolomide and suggest that targeting this pathway may be beneficial for overcoming resistance.
ZVT high step‐up DC/DC converter with a novel passive snubber cell
Authors: Zhu Binxin , Ren Lulu , Wu Xi , Song Kun 
Published: December 2016

A zero voltage turn‐off high step‐up DC/DC converter is presented. The conversion efficiency and power density are improved significantly by using a novel passive snubber cell, which only consists of two diodes and a snubber capacitor. The converter also provides high‐voltage conversion ratio as well as low‐voltage stress on switches and diodes, which make it suitable for some special industrial applications as electric‐vehicle, uninterruptible power supply system or photovoltaic power generation system. The topology, operation principles and performance characteristics are analysed in detail. Moreover, a maximum 800 W experimental prototype has been developed to validate the effectiveness of the theoretical analysis, and 96.2% efficiency has been achieved.
A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome
Authors: Benjamin Joel S. , Pilarowski Genay O. , Carosso Giovanni A. , Zhang Li , Huso David. L. , Goff Loyal A. , Vernon Hilary J. , Hansen Kasper D. , Bjornsson Hans T. 
Published: December 2016

SignificanceIntellectual disability is a common clinical entity with few therapeutic options. Kabuki syndrome is a genetically determined cause of intellectual disability resulting from mutations in either of two components of the histone machinery, both of which play a role in chromatin opening. Previously, in a mouse model, we showed that agents that favor chromatin opening, such as the histone deacetylase inhibitors (HDACis), can rescue aspects of the phenotype. Here we demonstrate rescue of hippocampal memory defects and deficiency of adult neurogenesis in a mouse model of Kabuki syndrome by imposing a ketogenic diet, a strategy that raises the level of the ketone beta-hydroxybutyrate, an endogenous HDACi. This work suggests that dietary manipulation may be a feasible treatment for Kabuki syndrome.
Modifications to aLATE MERISTEM IDENTITY1gene are responsible for the major leaf shapes of Upland cotton (Gossypium hirsutumL.)
Authors: Andres Ryan J. , Coneva Viktoriya , Frank Margaret H. , Tuttle John R. , Samayoa Luis Fernando , Han Sang-Won , Kaur Baljinder , Zhu Linglong , Fang Hui , Bowman Daryl T. , Rojas-Pierce Marcela , Haigler Candace H. , Jones Don C. , Holland James B. , Chitwood Daniel H. , Kuraparthy Vasu 
Published: December 2016

SignificanceLeaves are the primary source of photoassimilate in crop plants. A precise understanding of the genetic architecture underlying leaf morphology is critical to engineering climate-resilient crop varieties. An ideal cotton cultivar would produce a lower canopy of broad,normalleaves before transitioning to an upper canopy of highly lobed,okraleaves. Here we show that the major leaf shapes of cotton are controlled by theokralocus, which encodes an HD-Zip transcription factorGossypium hirsutumLATE MERISTEM IDENTITY1-D1b(GhLMI1-D1b). Using gene silencing, we temporarily induced normal leaf formation inokra, thus validating the candidate gene and creating the leaf shape ideotype in cotton. This study, identifying a single locus responsible for cotton leaf shape, expands the genetic toolbox for breeders to produce superior cotton varieties.
Quantifying Elements in Arctic Grayling and Bull Trout in the South Nahanni River Watershed, Northwest Territories, Using Nonlethal Tissue Samples
Authors: Anderson Julie , Scrimgeour Garry , Palace Vince , Suitor Michael , Wilcockson John 
Published: December 2016

Abstract
Monitoring of contaminants in fish generally involves lethal sampling, but public scrutiny and increased pressure on fisheries have driven the need to develop nonlethal sampling methods. We examined the ability of adipose, anal, and caudal fin tissues to serve as nonlethal surrogates for lethal muscle tissue samples in the analysis of metals (elements). First, we evaluated the use of biopsies by examining relationships between concentrations of 39 elements in low-volume dorsal muscle biopsies and high-volume muscle samples from Arctic Grayling Thymallus arcticus and Bull Trout Salvelinus confluentus collected in the South Nahanni River watershed, Northwest Territories, Canada. Low-volume dorsal biopsy samples in this study served to most closely model the concentrations of elements found in high-volume dorsal samples; caudal and anal fins were more representative of high-volume dorsal samples than were adipose fins. Regressions between high- and low-volume dorsal muscle samples were significant for 12 elements/species, with Cs, Rb, and Tl having the strongest relationships in both species. Regression analyses comparing low-volume muscle samples and fin samples revealed variation between Arctic Grayling and Bull Trout, but Co, Hg, and Tl concentrations among samples were strongly related for both species. Addition of fish length or age as a covariate did not greatly improve the predictive power of calculated regressions. For future monitoring, selection of a nonlethal sampling strategy (e.g., use of dorsal biopsy or adipose fin samples) will require consideration of the element of interest, the primary route of exposure, interaction with other elements, and the basic biology and ecology of the fish species. Ideally, nonlethal sampling tools can be further developed for the two species to promote inclusion of community partners; these tools offer sustainable, long-term approaches for monitoring sensitive fish populations in northern Canadian habitats.
Received February 29, 2016; accepted September 9, 2016Published online December 20, 2016
Sexual mimicry
Authors: Johnson Steven D. , Schiestl Florian P. 
Published: December 2016

AbstractSexual mimicry involves extensive floral modifications, particularly the evolution of highly specialized volatile signals to attract male insects. The study of sexual mimicry in plants has given new insights into insect reproductive biology and provides some of the best examples of pollinator-mediated plant speciation. This chapter reviews the occurrence of sexual mimics among plants and the most commonly recruited groups of pollinators. It shows which signals are the most important and how they evolve. Next, the evidence is reviewed for pollinator shifts and how they may drive speciation in this highly specific pollination system. It also discusses how the typically low genetic differentiation between species of sexual mimics can be interpreted. Finally, the factors that drive the evolution of sexual mimicry in different plant lineages are considered.
Elastic Behavior of Solids
Authors: Ketterson J. B. 
Published: December 2016

Abstract
This chapter analyzes the response of solids to stress. The defining property of a solid is its ability to resist shape changes in the presence of external stresses. Stress, defined as force per unit area, can be divided into two classes: compression and shear. The remainder of the chapter derives expressions for the following: stress tensor, strain tensor, Hooke’s law, energy density, elastic module of cubic and hexagonal systems, distortions of a cubic crystal, elastic waves, elastic waves in a cubic crystal, isotropic media, viscosity in solids, and the measurement of elastic constants of materials. Sample problems are also provided at the end of the chapter.
Electric Behavior of Insulators
Authors: Ketterson J. B. 
Published: December 2016

Abstract
Maxwell’s theory of electromagnetism in free space involves two fields: the electric field, E, and the magnetic field, M. When material media are present two more fields are introduced: the electric displacement, D, and the magnetic induction, B, for a total of four, all of which are position dependent in general. E and D are related through a third field, the polarization field, P, according to D = E + 4πP in c.g.s. units. P arises from a distribution of microscopic electric dipoles within the material. This chapter focuses on electric behaviours associated with the two fields. It discusses the potential from a distribution of dipoles; the local electric field; the dielectric constant; orientational polarization; and dielectric relaxation. Sample problems are also provided at the end of the chapter.
Metals and the Drude–Lorentz Model
Authors: Ketterson J. B. 
Published: December 2016

Abstract
In its more modern context, the Drude–Lorentz model views a material as consisting of an array of the following: fixed positive ions and free electrons; or neutral atoms, or balanced positive and negative ions atoms (as in NaCl), with no free electrons. The first case involves a metal while the second involves an insulator. This chapter derives expressions for the following: electrical conductivity and electrical resistivity of metals at room temperature; the Hall effect; frequency-dependent conductivity; dielectric constant of a metal; dielectric constant of an insulator, a metal in a constant magnetic field and an oscillatory electric field; thermal conductivity of a metal; and thermoelectric effect. The chapter also includes some sample problems.
Elementary Theories of the Thermal Properties of Solids
Authors: Ketterson J. B. 
Published: December 2016

Abstract
This chapter discusses the thermal properties of solids. A fundamental thermodynamic property of a body is its heat capacity, C ≡ dQ/dT, where dQ is an increment of heat transferred to the body and dT is the associated temperature change. When measured at constant volume (where no work is done by the sample on its environment), the heat added goes directly into increasing the internal energy, E. The internal energy is computed using the methods of statistical physics; which is briefly summarized. The remainder of the chapter analyzes the equipartition law for free and bound particles; the lattice heat capacity at low temperatures or the Einstein model; and the Debye model. Sample problems are also provided at the end of the chapter.
Elementary Theories of Magnetism
Authors: Ketterson J. B. 
Published: December 2016

Abstract
This chapter discusses the magnetic properties of matter. All materials are either diamagnetic or paramagnetic; hence diamagnetic materials tend to exclude flux while paramagnetic materials tend to gather flux. Superconductors and (soft) ferromagnets are extreme limits of these behaviors. The presence of a non-zero susceptibility depends ultimately on quantum effects — strictly classical systems cannot be magnetic, although a semi-classical theory works well for many situations. The chapter first analyzes the semi-classical theories of diamagnetism (Langevin diamagnetism) and paramagnetism (Langevin paramagnetism). It then covers the quantum theory of magnetism; quantum theory of non-interacting spins; adiabatic demagnetization; chemical bonding, Hund’s rules and magnetic ions; and magnetic moments of 4f and 3d ions. Sample problems are also provided at the end of the chapter.
Elementary Theories of Crystal Bonding
Authors: Ketterson J. B. 
Published: December 2016

Abstract
This chapter discusses several highly simplified models that have been used historically to discuss crystal bonding. It is customary to divide materials into categories according to the qualitative nature of the chemical or physical bonding existing among the atoms. The ‘dividing line’ between these categories is not always sharp. For instance bonding in transition metals, such as tungsten, may be thought of as both metallic and covalent. The remainder of the chapter discusses simple models of the van der Waals bond, ionic bond, covalent bond, and metallic bond. The chapter also includes some sample problems.