bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking variation in intrinsic water‐use efficiency to isohydricity: a comparison at multiple spatiotemporal scales
Authors: Yi Koong , Maxwell Justin T. , Wenzel Matthew K. , Roman D. Tyler , Sauer Peter E. , Phillips Richard P. , Novick Kimberly A.
Published: August 2018

Species‐specific responses of plant intrinsic water‐use efficiency (iWUE) to multiple environmental drivers associated with climate change, including soil moisture (θ), vapor pressure deficit (D), and atmospheric CO2 concentration (ca), are poorly understood.

We assessed how the iWUE and growth of several species of deciduous trees that span a gradient of isohydric to anisohydric water‐use strategies respond to key environmental drivers (θ, D and ca). iWUE was calculated for individual tree species using leaf‐level gas exchange and tree‐ring δ13C in wood measurements, and for the whole forest using the eddy covariance method.

The iWUE of the isohydric species was generally more sensitive to environmental change than the anisohydric species was, and increased significantly with rising D during the periods of water stress. At longer timescales, the influence of ca was pronounced for isohydric tulip poplar but not for others.

Trees’ physiological responses to changing environmental drivers can be interpreted differently depending on the observational scale. Care should be also taken in interpreting observed or modeled trends in iWUE that do not explicitly account for the influence of D.
Financial Instruments for Mitigation of Flood Risks: The Case of Florence
Authors: Castelli Fabio , Galeotti Marcello , Rabitti Giovanni
Published: August 2018

This article analyzes the mechanisms and effects of innovative financial instruments that a central public administration (CPA) may adopt to minimize the flood risk in particularly exposed regions. The pattern we suggest assumes that in risky areas the CPA can issue two financial instruments, called project options and CAT‐bonds, producing a dynamic interaction among three types of agents: the CPA itself, the local public administrations, and private investors. We explore the possible scenarios of such interaction and the conditions under which the CPA's goal of maximal risk reduction is attained. This pattern is proposed for flood risk mitigation in the city of Florence, where the model dynamics are tested assuming parameters obtained from engineering studies.
The HLA‐C*01:32:02 allele identified in a volunteer donor for hematopoietic stem cell transplant
Authors: Baek In‐Cheol , Choi Eun‐Jeong , Shin Dong‐Hwan , Kim Hyoung‐Jae , Kim Tai‐Gyu
Published: August 2018

HLA‐C*01:32:02 differs from HLA‐C*01:02:01:01 in codons 131 and 135 in exon 3.
Daily heliotropic movements assist gas exchange and productive responses in DREB1A soybean plants under drought stress in the greenhouse
Authors: Rakocevic Miroslava , Müller Mariele , Matsunaga Fabio Takeshi , Neumaier Norman , Farias José Renato Bouças , Nepomuceno Alexandre Lima , Fuganti‐Pagliarini Renata
Published: August 2018

Drought stress is one of the most severe environmental constraints on plant production. Under environmental pressures, complex daily heliotropic adjustments of leaflet angles in soybean can help to reduce transpiration losses by diminishing light interception (paraheliotropism), increase diurnal carbon gain in sparse canopies and reduce carbon gain in dense canopies by solar tracking (diaheliotropism). The plant materials studied were cultivar BR 16 and its genetically engineered isoline P58, ectopically overexpressing AtDREB1A, which is involved in abiotic stress responses. We aimed to follow the movements of central and lateral leaflets in vegetative stages V7–V10 and reproductive stages R4–R5, integrating the reversible morphogenetic changes into an estimate of daily plant photosynthesis using three‐dimensional modeling, and to analyze the production parameters of BR 16 and P58. The patterns of daily movements of central leaflets of BR 16 in V7–V10 and R4–R5 were similar, expressing fewer diaheliotropic movements under drought stress than under non‐limiting water conditions. Daily heliotropic patterns of lateral leaflets in V7–V10 and R4–R5 showed more diaheliotropic movements in drought‐stressed P58 plants than in those grown under non‐limiting water conditions. Leaf area in R4–R5 was generally higher in P58 than in BR 16. Drought significantly affected gas exchange and vegetative and reproductive architectural features. DREB1A could be involved in various responses to drought stress. Compared with the parental BR 16, P58 copes with drought through better compensation between diaheliotropic and paraheliotropic movements, finer tuning of water‐use efficiency, a lower transpiration rate, higher leaf area and higher pod abortion to accomplish the maximum possible grain production under continued drought conditions.
Adipose‐derived stem cells and the stromal vascular fraction in polyglycolic acid‐collagen nerve conduits promote rat facial nerve regeneration
Authors: Shimizu Mari , Matsumine Hajime , Osaki Hironobu , Ueta Yoshifumi , Tsunoda Satoshi , Kamei Wataru , Hashimoto Kazuki , Niimi Yosuke , Watanabe Yorikatsu , Miyata Mariko , Sakurai Hiroyuki
Published: August 2018

Adipose‐derived stem cells (ADSCs) and the stromal vascular fraction (SVF) promote nerve regeneration. Biodegradable nerve conduits are used to treat peripheral nerve injuries, but their efficiencies are lower than those of autologous nerve grafts. This study developed biodegradable nerve conduits containing ADSCs and SVF and evaluated their facial nerve regenerating abilities in a rat model with a 7‐mm nerve defect. SVF and ADSCs were individually poured into nerve conduits with polyglycolic acid‐type I collagen as a scaffold (ADSCs and SVF groups). The conduits were grafted on to the nerve defects. As the control, the defect was bridged with polyglycolic acid‐collagen nerve conduits without cells. At 13 weeks, after transplantation, the regenerated nerves were evaluated physiologically and histologically. The compound muscle action potential of the SVF group was significantly higher in amplitude than that of the control group. Electron microscopy showed that the axon diameter of the SVF group was the largest, followed by the ADSC group and control group with significant differences among them. The SVF group had the largest fiber diameter, followed by the ADSC group and control group with significant differences among them. The ADSC group had the highest myelin thickness, followed by the SVF group and control group with significant differences among them. Identical excellent promoting effects on nerve regeneration were observed in both the ADSC and SVF groups. Using SVF in conduits was more practical than using ADSCs because only the enzymatic process was required to prepare SVF, indicating that SVF could be more suitable to induce nerve regeneration.
Pig tracheal patchy xenotransplantation in the dog
Authors: Lee Tae‐Ki , Kim Jong‐Min , Choi Seok Hwa
Published: August 2018

Background

A long‐segmental tracheal lesion is difficult to repair by tracheal allotransplantation due to the lack of a well‐defined blood supply for blood vessel anastomosis. The donor trachea needs to be revascularized within a well‐vascularized soft tissue flap for several months to allow successful trachea allotransplantation. To date, xenotransplantation using the wild‐type or genetically modified pig has been widely studied. The object of this study was to evaluate the feasibility of a small‐sized (2 × 2 cm) wild‐type pig tracheal patchy in a dog tracheal defect model before trying a long‐segment tracheal defect model and using a genetically modified pig as a donor in dog xenotransplantation.

Method

Three healthy beagle dogs (8‐9 kg) were used as recipients, and one pig (20 kg) was used as the donor. A pig cartilaginous tracheal patchy (2 × 2 cm half tube) was sutured to the tracheal resected site in each dog. Antithymocyte globulin (2.5 mg/kg infusion, D0 and 1), tacrolimus (4.5 mg/kg, twice a day for 2 months), and methylprednisolone sodium succinate (1 mg/kg, IV, for 2 days and tapering) were administered for immunosuppression. The levels IL‐2 and IFN‐γ in the serum were measured at D0, 7, and 28. Tracheoscopy was performed at D28, 60, and 90. The recipients were sacrificed at D90, and the expression of dog and pig genes in the graft was evaluated by PCR. Histopathological examination of the graft was conducted.

Results

All of the dogs survived without complications during the experimental period. Their IL‐2 and IFN‐γ levels were significantly increased at D7 after transplantation compared to D0 and D28 (P < 0.05). The pig tracheal patchy site was open, and no stenosis was observed until D90 on tracheoscopy, when pale mucosa erosion was observed; there was also remnant suture material at D28. However, the tracheal patchy sites gradually became similar to normal mucosa at D60 and 90. The expression of pig genes was detected in the graft by PCR. Normal epithelium and CD3 cells were observed in the histological examination at D90.

Conclusion

In this study, our data suggest that the pig tracheal patchy can be successfully engrafted into the trachea of dog, although erosion of mucosa on the graft was seen at D30, in spite of the discordant species.
Investigating the Theoretical Structure of Deliberative Democratic Leadership
Authors: Lin Chun-wen
Published: August 2018

This paper explores the theoretical framework of teaching deliberative democratic leadership by examining teacher deliberative competency from theories of deliberative democracy. The research described the theoretical framework of deliberative democratic leadership as a heuristic in the practice of teaching deliberative democratic leadership. Through exploratory factor analysis, Teacher Deliberative Competency Scale (TDCS) reduced to 7-factor structure: ethic, inclusion, well-informed, publicity, deliberation, reciprocity and consensus. Results suggest that TDCS provides instructions for teaching deliberative democratic leadership.
Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function
Authors: Salazar E. R. , Richter H. G. , Spichiger C. , Mendez N. , Halabi D. , Vergara K. , Alonso I. P. , Corvalán F. A. , Azpeleta C. , Seron‐Ferre M. , Torres‐Farfan C.
Published: August 2018

Key points

Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy.

Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function.

We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels.

The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases.

Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long‐term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down‐regulated and 437 up‐regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48–20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long‐term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.
The effects of ultrasound parameters and microbubble concentration on acoustic particle palpation
Authors: Saharkhiz Niloufar , Koruk Hasan , Choi James J.
Published: August 2018

The elasticity of tissue—an indicator of disease progression—can be imaged by ultrasound elasticity imaging technologies. An acoustic particle palpation (APP) has recently been developed—the use of ultrasonically driven acoustic particles (e.g., microbubbles)—as an alternative method of tissue deformation. APP has the potential to improve the resolution, contrast, and depth of ultrasound elasticity imaging; but the tissue displacement dynamics and its dependence on acoustic pressure, center frequency, and microbubble concentration remains unknown. Here, displacements of at least 1 μm were produced by applying ultrasound onto a microbubble solution (concentration: 10 × 106 microbubbles ml–1) placed within a tunnel surrounded by a 5% gelatin phantom. Displacements of more than 10 μm were produced using a 1, 3.5, or 5 MHz center frequency pulse with peak-rarefactional pressures of 470, 785, and 1210 kPa, respectively. The deformation of the distal wall varied spatially and temporally according to the different parameters investigated. At low pressures, the deformation increased over several milliseconds until it was held at a nearly constant value. At high pressures, a large deformation occurred within a millisecond followed by a sharp decrease and long stabilization. Ultrasound exposure in the presence of microbubbles produced tissue deformation (p < 0.05) while without microbubbles, no deformation was observed.
An analysis of the thickness vibration of an unelectroded doubly-rotated quartz circular plate
Authors: Xie Longtao , Wang Shaoyun , Zhang Chuanzeng , Wang Ji
Published: August 2018

The scalar differential equation in the thickness eigendisplacement for the doubly-rotated quartz plates is applied to analyze thickness vibrations of an unelectroded circular plate with free edges at the neighborhood of the pure thickness vibration mode. The scalar differential equation is transformed into an elliptical coordinate system. With the boundary conditions of free edges, the frequencies and the modes are solved in terms of the Mathieu function and the Modified Mathieu function. The results of frequencies of the fundamental harmonic and its third overtone of an AT-cut quartz circular plate by the present approach agree well with the existing theoretical results and the experiment results. The frequencies and modes of an SC-cut quartz circular plate are investigated by the present approach. The frequencies are close to each other when the order of the harmonics is the same. A rotation angle of the symmetric axes of the vibration modes are observed that is dependent on the anisotropic material constants and the order of the harmonics. This approach has potential applications in the design of the doubly-rotated quartz circular resonators.
Psychometric Properties of the Hindi Version of SPADI in Overhead Athletes With Shoulder Impingement Syndrome
Authors: Sharma Saurabh , Hussain M. Ejaz
Published: August 2018

Patient-related outcome measures are often used for assessing and determining management efficacy of shoulder impingement syndrome (SIS) in overhead athletes. This study was undertaken to examine the psychometric properties (structural validity, convergent validity, internal consistency, test-retest reliability, and minimal detectable change) and perform partial confirmatory factor analysis (PCFA) of the Hindi SPADI. Eighty male athletes with a mean age of 21.5 ± 2.20 years were enrolled in the study. Hindi SPADI test-retest reproducibility was calculated by intraclass correlation coefficient (ICC2,1), and Cronbach alpha helped determine internal consistency of the index. Pearson correlation coefficient compared the Hindi SPADI with the Hindi DASH scale to determine convergent validity, while the measurement error was calculated by minimal detectable change (MDC95). Exploratory factor analysis utilized for assessing the structural validity of the index gave a five-factor solution, which explained 70.03% of the variances. The test-retest reliability (ICC2,1), internal consistency, and convergent validity were found to be high, at 0.87, 0.75, and 0.94, respectively. The MDC95 was calculated to be 14.20. Additionally, the PCFA confirmed the five-factor solution with fit indices. This Hindi version of SPADI demonstrated satisfactory psychometric properties in overhead athletes with shoulder impingement syndrome.
Association Between Preseason Training and Performance in Elite Australian Football
Authors: McCaskie Callum J. , Young Warren B. , Fahrner Brendan B. , Sim Marc
Published: August 2018

Purpose: To examine the association between preseason training variables and subsequent in-season performance in an elite Australian football team. Methods: Data from 41 elite male Australian footballers (mean [SD] age = 23.4 [3.1] y, height =188.4 [7.1] cm, and mass = 86.7 [7.9] kg) were collected from 1 Australian Football League (AFL) club. Preseason training data (external load, internal load, fitness testing, and session participation) were collected across the 17-wk preseason phase (6 and 11 wk post-Christmas). Champion Data© Player Rank (CDPR), coaches’ ratings, and round 1 selection were used as in-season performance measures. CDPR and coaches’ ratings were examined over the entire season, first half of the season, and the first 4 games. Both Pearson and partial (controlling for AFL age) correlations were calculated to assess if any associations existed between preseason training variables and in-season performance measures. A median split was also employed to differentiate between higher- and lower-performing players for each performance measure. Results: Preseason training activities appeared to have almost no association with performance measured across the entire season and the first half of the season. However, many preseason training variables were significantly linked with performance measured across the first 4 games. Preseason training variables that were measured post-Christmas were the most strongly associated with in-season performance measures. Specifically, total on-field session rating of perceived exertion post-Christmas, a measurement of internal load, displayed the greatest association with performance. Conclusion: Late preseason training (especially on-field match-specific training) is associated with better performance in the early season.
Plasma and Intrapulmonary Concentrations of ETX2514 and Sulbactam following Intravenous Administration of ETX2514SUL to Healthy Adult Subjects
Authors: Rodvold Keith A. , Gotfried Mark H. , Isaacs Robin D. , O'Donnell John P. , Stone Emily
Published: August 2018

ETX2514 is a novel β-lactamase inhibitor that broadly inhibits Ambler class A, C, and D β-lactamases. ETX2514 combined with sulbactam (SUL)in vitrorestores sulbactam activity againstAcinetobacter baumannii.
RocA Has Serotype-Specific Gene Regulatory and Pathogenesis Activities in Serotype M28 Group A Streptococcus
Authors: Bernard Paul E. , Kachroo Priyanka , Zhu Luchang , Beres Stephen B. , Eraso Jesus M. , Kajani Zaid , Long S. Wesley , Musser James M. , Olsen Randall J.
Published: August 2018

Serotype M28 group A streptococcus (GAS) is a common cause of infections such as pharyngitis (“strep throat”) and necrotizing fasciitis (“flesh-eating” disease). Relatively little is known about the molecular mechanisms underpinning M28 GAS pathogenesis.
An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases in Myxococcus xanthus DK1622
Authors: Esquilín-Lebrón Karla J. , Boynton Tye O. , Shimkets Lawrence J. , Thomas Michael G.
Published: August 2018

MbtH-like proteins (MLPs) are essential accessory proteins for the function of many nonribosomal peptide synthetases (NRPSs). We identified 50 MLPs from diverse bacteria that are coded by genes that are not located near any NRPS-encoding biosynthetic gene clusters (BGCs). We define these as orphan MLPs because their NRPS partner(s) is unknown. Investigations into the orphan MLP from
Myxococcus xanthus
DK1622 determined that it interacts with NRPSs from at least seven distinct BGCs. Support for these MLP-NRPS interactions came from the use of a bacterial two-hybrid assay and copurification of the MLP with various NRPSs. The flexibility of this MLP to naturally interact with multiple NRPSs led us to hypothesize that this MLP may be used as a “universal” MLP during the construction of functional hybrid NRPSs.
Phosphorylated VP30 of Marburg Virus Is a Repressor of Transcription
Authors: Tigabu Bersabeh , Ramanathan Palaniappan , Ivanov Andrey , Lin Xionghao , Ilinykh Philipp A. , Parry Christian S. , Freiberg Alexander N. , Nekhai Sergei , Bukreyev Alexander
Published: August 2018

The largest outbreak of MARV occurred in Angola in 2004 to 2005 and had a 90% case fatality rate. There are no approved treatments available for MARV. Development of antivirals as therapeutics requires a fundamental understanding of the viral life cycle. Because of the close similarity of MARV to another member of
Filoviridae
family, EBOV, it was assumed that the two viruses have similar mechanisms of regulation of transcription and replication. Here, characterization of the role of VP30 and its phosphorylation sites in transcription of the MARV genome demonstrated differences from those of EBOV. The identified phosphorylation sites appeared to inhibit transcription and appeared to be involved in interaction with both NP and VP35 ribonucleoproteins. A small molecule targeting PP1 inhibited transcription of the MARV genome, effectively suppressing replication of the viral particles. These data demonstrate the possibility developing antivirals based on compounds targeting PP1.
Two subtypes of symptomatic joint hypermobility: a descriptive study using latent class analysis
Authors: Di Mattia Francesco , Fary Robyn , Murray Kevin J , Howie Erin , Smith Anne , Morris Susan
Published: August 2018

Objective

To investigate a cohort of children with symptomatic joint hypermobility.

Methods

Case notes for 318 children with joint hypermobility attending a rheumatology clinic were reviewed for clinical presentation, medical history, psychosocial factors and physical examination findings. Seven key variables were extracted and used as indicator variables in a latent class analysis to estimate the presence and number of subgroups of children with symptomatic joint hypermobility.

Results

Two subgroups with differing clinical presentations were identified accounting for age and gender: an ‘athletic-persistent’ class (62%) characterised by higher probabilities for recurrent and chronic musculoskeletal pain, and less severe hypermobility; and a ‘systemic-profound’ class (38%) characterised by generalised hypermobility, recurrent musculoskeletal pain, gastro-oesophageal reflux and motor delay.

Conclusion

Findings suggest the presence of two distinct presentations of children with hypermobility. This finding may be important for clinical decision-making and management of this group of children.
Global microarray profiling identifiedhsa_circ_0064428as a potential immune-associated prognosis biomarker for hepatocellular carcinoma
Authors: Weng Qiaoyou , Chen Minjiang , Li Maoquan , Zheng Yong-Fa , Shao Guoliang , Fan Weijun , Xu Xi-Ming , Ji Jiansong
Published: August 2018

Background

Increasing evidence has shown that circular RNAs (circRNAs) are involved tumourigenesis and metastasis of hepatocellular carcinoma (HCC); however, progression about its function in HCC is relatively slow. Here, we aimed to investigate whether plasma circRNAs could reflect the tumour-infiltrating lymphocytes (TILs) in HCC tumour tissues and serve as prognosis biomarker for HCC.

Methods

Tissue samples of patients with HCC were subjected to immunohistochemistry staining against CD8 to examine the TILs. Then, we investigated the expression profile of circRNAs by microarray between plasma of patients with HCC with high TILs and low TILs, and the differentially expressed circRNAs were validated with qRT-PCR. Statistical analysis was performed with SPSS software and GraphPad Prism.

Results

We have demonstrated that patients with HCC with high TILs exhibit a significant better overall survival, suggesting clinical outcome could be predicted by TILs. Global circRNA microarray between plasma of patients with HCC with high TILs and low TILs successfully identified six differentially expressed novel circRNAs. Among them, the expression ofhsa_circ_0064428was significantly reduced in patients with HCC with high TILs but increased in patients with low TILs. Moreover,hsa_circ_0064428was negatively correlated with patient’s survival, tumour size and metastasis.

Conclusion

These findings together imply thathsa_circ_0064428could be considered as a potential HCC prognosis biomarker. Future in-depth research is required to further illustrate the involvement ofhsa_circ_0064428in HCC tumourigenesis and metastasis.
A time simulated annealing-back propagation algorithm and its application in disease prediction
Authors: Hu Fang , Wang Mingzhu , Zhu Yanhui , Liu Jia , Jia Yalin
Published: August 2018

In this paper, based on the Back Propagation (BP) neural network algorithm, we introduce the idea of the Simulated Annealing (SA), and then propose a new neural network algorithm: Time Simulated Annealing-Back Propagation (TSA-BP) algorithm. The proposed algorithm can improve the convergence rate and numerical stability. By using this proposed algorithm, the learning rates and initial weights in the BP neural network could be easily adjusted. We show that the TSA-BP algorithm could reduce the errors caused by human-made factors. Several numerical experiments have been tested by using different disease data. Furthermore, we compared the TSA-BP algorithm to the other existing, well-known algorithms. Numerical results show higher accuracy and efficiency of the TSA-BP algorithm.
IP Over SONET/SDH Link-Layer Processing with Multiprocessor
Authors: Zuo Zhen , Liu Desheng , Qin Jiangyi , Huang Zhiping , Su Shaojing
Published: August 2018

With the recent increase in IP traffic owing to fiber communication, previous schemes have become inadequate for link-layer processing of IP over SONET/SDH(POS). In this study, a proposal based on [Formula: see text] processors to provide mapping or demapping of IP datagrams from or into SONET/SDH is presented, and the value of [Formula: see text] is decided based on the link layer rate of POS. Further, the mathematic model of proposed architecture are presented in detail. Then the realization procedures are implemented in a Field-Programmable Gate Array (FPGA). Both theoretical analysis and experimental test prove that the proposed scheme is efficient, portable, cost-efficient and has a lower hardware resources consumption.
Charged slowly rotating toroidal black holes in the (1 + 3)-dimensional Einstein-power-Maxwell theory
Authors: Panotopoulos Grigoris , Rincón Ángel
Published: August 2018

In this work, we find charged slowly rotating solutions in the four-dimensional Einstein-power-Maxwell nonlinear electrodynamics assuming a negative cosmological constant. By solving the system of coupled field equations explicitly, we obtain an approximate analytical solution in the small rotation limit. The solution obtained is characterized by a flat horizon structure, and it corresponds to a toroidal black hole. The Smarr’s formula, the thermodynamics and the invariants Ricci scalar and Kretschmann scalar are briefly discussed.
Analysis of the neutron spin structure function g1n by using the Laplace transform technique
Authors: Teimoury Azadbakht F. , Boroun G. R. , Rezaei B.
Published: August 2018

In this paper, the polarized neutron structure function [Formula: see text] in the [Formula: see text] nucleus is investigated and an analytical solution based on the Laplace transform method for [Formula: see text] is presented. It is shown that the neutron spin structure function can be extracted directly from the polarized nuclear structure function of [Formula: see text]. The nuclear corrections due to the Fermi motion of the nucleons as well as the binding energy considerations are taken into account within the framework of the convolution approach and the polarized structure function of [Formula: see text] nucleus is expressed in terms of the spin structure functions of nucleons and the light-cone momentum distribution of the constituent nucleons. Then, the numerical results for [Formula: see text] are compared with experimental data of the SMC and HERMES collaborations. We found that there is an overall good agreement between the theory and experiments.
Abstract A008: Establishment of novel gastric cancer PDX models and cell lines for developing new therapeutics
Authors: Kuwata Takeshi , Yanagihara Kazuyoshi
Published: August 2018

It is essential to have appropriate preclinical models for developing new drugs for gastric cancer (GC). Cell lines have been the most commonly used model for this purpose. However, the numbers of gastric cancer cell lines established and available for this purpose are limited and not enough to deal with variety of gastric cancer molecular subtypes such as recently proposed by The Cancer Genome Atlas (TCGA). In addition, patient-derived xenograft (PDX) models have been considered more appropriate models for evaluating the efficacy of new drugs in vivo. For contributing to develop new drugs as well as to seek more effective biomarkers, we have been conducting an intramural project, called DEF study, for establishing new GC PDXs as well as new GC cell lines. So far, 30 multi-passage-competent new PDXs have been successfully established from surgically removed gastric cancer tissues or ascites. Twenty-two (22) new GC cell lines have also been established from PDX tissue (16 lines) or directly from ascites (6 lines). All GC PDXs have been examined by immunohistochemistry for HER2, EGFR, and Met expressions, and we identified 5 cases overexpressing HER2 (corresponding to Score3+) and 1 case overexpressing both EGFR and MET. Comprehensive gene mutation analysis has been performed in 21 PDX tissues, and repetitive mutations (SNV/Indel) have been observed in ERBB2, ERBB3, BRAF, APC, ARID1A, and p53. Copy number alternations have also been identified; examples include KRAS and ERBB2 for amplification and PTEN and CDKN2A for deletion.

Citation Format: Takeshi Kuwata, Kazuyoshi Yanagihara. Establishment of novel gastric cancer PDX models and cell lines for developing new therapeutics [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A008.
Abstract A017: Optimization of a cachexia animal model for efficacy evaluation of candidates
Authors: Bae Jiyeong , Cho Ig Jun , Shin Jung Hyu , Yuh Hyung Soo , Moon Hyung Ho , Lee Hye Lim , Jo Yeong Nang , Park Yeon Ju , Choi Woo Sung , Hyun Byung Hwa
Published: August 2018

Cachexia-anorexia syndrome, which is called cancer cachexia, is a common and important indicator of cancer and occurs in 30% to 80% of cancer patients. Cancer cachexia is characterized by a severe progressive body wasting, accompanied by loss of adipose tissue and skeletal muscle mass. The presence of cachexia is associated with a worsened prognosis and contributes to up to 20% of cancer deaths. In most cases, cancer cachexia patients clinically show anorexia caused through a complex system of hormones and neuropeptides. To investigate efficacy in development of new medicine, an optimized animal model is essentially required. Although several cancer cachexia animal models have been established, we focused on developing a better animal model particularly for efficacy evaluation with advanced bioimaging evaluation methods. First of all, we confirmed that an appropriate mouse strain is CDF1 in comparison with DBA1 and Balb/c after xenografting of Colon26. As the second step, we checked cell numbers with pattern of tumor growth. In human clinics, cure of cancer cachexia is usually performed with surgical removal of tumor. To make the animal model similar to clinical circumstances, we tested recovery time and pattern after removal of tumor. With optimized mouse model we tested efficacy of anticancer drug Megace 200 mg/kg as a positive control. In addition, we applied advanced bioimaging equipment such as MRI and CT to visualize actual tumor and fat with body composition. We expect that optimized animal model of cancer cachexia will prepare the way for more accurate efficacy test in preclinical state to go to a clinical trial.

Citation Format: Jiyeong Bae, Ig Jun Cho, Jung Hyu Shin, Hyung Soo Yuh, Hyung Ho Moon, Hye Lim Lee, Yeong Nang Jo, Yeon Ju Park, Woo Sung Choi, Byung Hwa Hyun. Optimization of a cachexia animal model for efficacy evaluation of candidates [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A017.
Abstract A039: FGF/PTX3 crosstalk in bladder cancer: novel prognostic and therapeutic implications
Authors: Matarazzo Sara , Maccarinelli Federica , Ghedini Gaia Cristina , Melocchi Laura , Bugatti Mattia , Vermi William , Presta Marco , Ronca Roberto
Published: August 2018

Bladder cancer is one of the most common cancers in the world. Although most of urothelial carcinomas (UCs) are low-grade papillary tumors, their propensity to recur and to progress to become invasive with a poor survival rate represents a major challenge. Different members of the Fibroblast growth factor (FGF) family are expressed by human bladder cancer cells, and aberrant expression of FGF receptors (FGFRs) is a typical feature of bladder cancer compared to normal urothelium. High expression levels of FGFR1 are associated with poor survival and FGFR3 is frequently dysregulated in UC. Thus, the FGF/FGFR system may represent a promising therapeutic target in invasive and noninvasive bladder cancer.

Long-pentraxin 3 (PTX3) acts as a natural FGF trap by binding FGFs and hampering their biologic activity in various tumor models. Preliminary observations have shown that low-grade UCs express PTX3 while high-grade/invasive UCs lose PTX3 expression. Accordingly, bladder cancer cell lines share an overall presence of FGFRs and FGFs but express different levels of PTX3 in vitro and in vivo. Of note, high-grade/invasive cells express very low or undetectable levels of PTX3, whereas low-grade, papilloma-like cells express high levels of PTX3. Indeed, invasive bladder cancer cell xenografts grow faster in nude mice and express much lower levels of PTX3 than low grade-derived lesions, thus confirming an inverse correlation between UC grade and PTX3 expression. This hypothesis is reinforced by a preliminary case study performed on a small cohort of biopsies from UC patients confirming that the presence of PTX3 is a common feature of low-grade samples while PTX3 is poorly expressed or absent in aggressive/invasive cases. These data point to PTX3 as a natural FGF trap that could play a role in modulating bladder cancer progression and invasiveness and indicate that inhibition of the FGF/FGFR system by natural and synthetic FGF traps may represent a promising target for the therapy of UCs.

Citation Format: Sara Matarazzo, Federica Maccarinelli, Gaia Cristina Ghedini, Laura Melocchi, Mattia Bugatti, William Vermi, Marco Presta, Roberto Ronca. FGF/PTX3 crosstalk in bladder cancer: novel prognostic and therapeutic implications [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A039.
Abstract A064: MiR-2861 behaves as a LCSCs biomarker and regulates the HDAC5-ERK system genes
Authors: Zhu Yimin , Zhao Mengya
Published: August 2018

Cancer stem cells (CSCs) are responsible for cancer initiation, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs may be helpful for early diagnosis and prognosis. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSCs differentiation model was established through introducing serum into the culture medium of H460 spheres. MiR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells. HDAC5 expression was positively correlated with miR-2861 in LCSCs and knockdown of miR-2861 decreased the expression of HDAC5, which implied that HDAC5 may be involved in the differentiation of LCSCs mediated by miR-2861. The role of HDAC5 in the regulation of differentiation of LCSCs was further verified by the inhibitory effect of LMK-235 on the phosphorylation of ERK1/2, which was recognized as the regulator of CSCs differentiation. Our study provided a better understanding of miR-2861 and HDAC5 axis in maintaining the stemness of LCSCs and laid a foundation for molecular targeted therapy.

Citation Format: Yimin Zhu, Mengya Zhao. MiR-2861 behaves as a LCSCs biomarker and regulates the HDAC5-ERK system genes [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A064.
Abstract A073: Gemcitabine cotreatment enhances the therapeutic effect of prexasertib in HNSCC cells that are less sensitive to Chk1 inhibition single-agent therapy
Authors: Gadhikar Mayur A. , Myers Jeffrey N.
Published: August 2018

Prexasertib, a highly potent Chk1 inhibitor, has shown remarkable single-agent activity (IC50 < 5 nmol/L) in a subset of head and neck cancer (HNSCC) cells that are genomically predisposed to replication stress. Nevertheless, a broader application of this therapeutic strategy in HNSCC is hindered because many HNSCC cells lack innate susceptibility to replication stress and exhibit much higher IC50 values for prexasertib. Here we report that gemcitabine cotreatment markedly augments the therapeutic efficacy of prexasertib in HNSCC cells that are recalcitrant/less sensitive to Chk1 inhibition monotherapy. Mechanistic investigations revealed perturbation in the S phase progression and induction of replication stress markers that associated with decreased colony survival upon gemcitabine and prexasertib combination treatment. These results indicate that therapeutic utility of prexasertib could be further expanded in HNSCC through a combination treatment with gemcitabine.

Citation Format: Mayur A. Gadhikar, Jeffrey N. Myers. Gemcitabine cotreatment enhances the therapeutic effect of prexasertib in HNSCC cells that are less sensitive to Chk1 inhibition single-agent therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A073.
Abstract A122: Anti-Helicobacter pylori activity of a novel derivative of intervenolin
Authors: Kawada Manabu , Ohishi Tomokazu , Abe Hikaru , Hayashi Chigusa , Sakashita Chiharu , Ohba Shun-ichi , Inoue Hiroyuki , Igarashi Masayuki , Watanabe Takumi , Shibasaki Masakatsu
Published: August 2018

Helicobacter pylori (H. pylori) infection plays a critical role in pathogenesis of gastric ulcer and gastric cancer. Thus, the eradication of H. pylori could prevent the onset of these diseases. At present the standard therapy against H. pylori infection is a combination therapy of a proton pump inhibitor and two antibiotics such as clarithromycin and amoxicillin. However, there exist H. pylori strains that show resistance against these antibiotics. Furthermore, adverse effect of these antibiotics against intestinal bacteria is unavoidable. We previously discovered a novel compound, intervenolin, from the culture broth of Nocardia sp. ML96-86F2. Intervenolin is a very unique compound having both antitumor and anti-H. pylori activities. To create a potent anti-H. pylori compound, we synthesized various derivatives of intervenolin. Among them we identified compounds that show selective anti-H. pylori activity in vitro without effect on other bacteria including intestinal bacteria. Oral monotherapy of the derivative exerts a significant eradicative effect against H. pylori-infected mice more than the standard combination therapy. Taken together, we have successfully created a potent new anti-H. pylori compound.

Citation Format: Manabu Kawada, Tomokazu Ohishi, Hikaru Abe, Chigusa Hayashi, Chiharu Sakashita, Shun-ichi Ohba, Hiroyuki Inoue, Masayuki Igarashi, Takumi Watanabe, Masakatsu Shibasaki. Anti-Helicobacter pylori activity of a novel derivative of intervenolin [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A122.
Abstract A125: Fragment-based approach to develop small-molecule STAT3 transcription factor inhibitors
Authors: Nahar Kazi S. , Jamshidi Shirin , Thurston David E. , Rahman Khondaker Miraz
Published: August 2018

Oncogenic transcription factors are an increasingly important target for anticancer therapies, as inhibition could allow the “reprogramming” of tumor cells, leading to apoptosis or differentiation from the malignant phenotype. STAT3 induces the transcription of genes that control differentiation, inflammation, proliferation, and tumor cell invasion, and its overexpression has been implicated in many different tumor types. Although tumor cells are often dependent upon activation of STAT3, nontumor cells are fairly tolerant of loss of its function, most likely reflecting redundancies in normal signal transduction. Thus, STAT3 inhibitors have high therapeutic potential. A combination of advanced in silico design and pharmacophore-based approaches has been used to design a series of novel inhibitors capable of disrupting STAT3 dimerization by interacting with the hexapeptide pocket of the STAT3 SH2 domain of the protein. The medicinal chemistry optimized mature ligand library members showed a notable improvement in STAT3-dimerization inhibition potency, with activities ranging from 33% to 59% inhibition. The optimized compounds had submicromolar to low micromolar cytotoxicity in STAT3-dependent cell lines with good selectivity ratios between these cells and nontumor cells (e.g., WI38 and A4). A number of the most active compounds (e.g., 6.6, 6.10, and 6.13) were selected for molecular dynamics simulation studies, and for an evaluation of their ability to downregulate STAT3-dependent genes in the STAT3-dependent cell line MDA MB 231. In these experiments, they were found to be able to downregulate the STAT3-dependent genes survivin, cyclin D1, fascin, and BCL-2 in comparison to the housekeeping gene GAPDH. The most active compound, 6.6, was also evaluated in a preliminary in vivo efficacy study in immune-compromised mice bearing MDA MB 231 tumors, and was found to have significant in vivo antitumor properties. Although further work is required to confirm the proposed mechanism of action, efforts are now focused on identifying the most suitable candidate molecule to take forward to the clinic.

Citation Format: Kazi S. Nahar, Shirin Jamshidi, David E. Thurston, Khondaker Miraz Rahman. Fragment-based approach to develop small-molecule STAT3 transcription factor inhibitors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A125.
Abstract A135: IFIT1 and 3 modulate the drug sensitivity in human oral squamous cell carcinoma cells
Authors: Pidugu Vijaya Kumar , Wu Mei-Maan , Liu Chung-Ji , Lee Te-Chang
Published: August 2018

Interferon-induced protein with tetratricopeptide repeats (IFITs) family, well-known interferons stimulated genes, have multiple tetratricopeptide repeats with helix-turn-helix structural motifs that mediate a variety of protein-protein interactions. There are four IFIT genes that have been identified: IFIT1, IFIT2, IFIT3, and IFIT5 in humans. We have previously shown that IFIT2 inhibits oral squamous cell carcinoma (OSCC) metastasis. Alternatively, our recent studies revealed the involvement of IFIT1 and IFIT3 in the progression of OSCC. The study on IFIT5 was far from adequate. The failure of chemotherapy or targeted therapy was often associated with the intrinsic or acquired drug resistance. In the present study, we are investigating the role of IFIT1 and IFIT3 genes on drug resistance in OSCC cells. Our results showed that ectopic expression of IFIT1 and IFIT3 proteins in OSCC cells significantly increased the resistance to cisplatin, whereas they became highly susceptible to gefitinib, a tyrosine kinase inhibitor. Consistently, silencing of IFIT1 and IFIT3 by shRNA enhanced the sensitivity to cisplatin but resulted in increased resistance to gefitinib. We further demonstrated that enhanced expression of IFIT1 and IFIT3 significantly increased the levels of activated forms of AKT (p-AKT) and EGFR (p-EGFR), suggesting that AKT and EGFR signaling could be activated by IFIT1 and IFIT3. Our present results indicate that IFIT1 and IFIT3 may serve as a marker for precisely choosing right therapeutic agents for the treatment of patients with OSCC.

Citation Format: Vijaya Kumar Pidugu, Mei-Maan Wu, Chung-Ji Liu, Te-Chang Lee. IFIT1 and 3 modulate the drug sensitivity in human oral squamous cell carcinoma cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A135.