bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Inhibition of Helicobacter pylori Growth by Redox Cycling Phenylaminojuglones
Authors: Benites Julio , Toledo Héctor , Salas Felipe , Guerrero Angélica , Rios David , Valderrama Jaime A. , Calderon Pedro Buc
Published: April 2018

Infection by Helicobacter pylori increases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4‐naphthoquinone, prevents H. pylori growth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, and in vitro evaluation of a series of juglone derivatives, namely, 2/3‐phenylaminojuglones, as potential H. pylori growth inhibitors. Results show that 5 out of 12 phenylaminojuglones (at 1.5 μg/mL) were 1.5–2.2‐fold more active than juglone. Interestingly, most of the phenylaminojuglones (10 out of 12) were 1.1–2.8 fold more active than metronidazole, a known H. pylori growth inhibitor. The most active compound, namely, 2‐((3,4,5‐trimethoxyphenyl)amino)‐5‐hydroxynaphthalene‐1,4‐dione 7, showed significant higher halo of growth inhibitions (HGI = 32.25 mm) to that of juglone and metronidazole (HGI = 14.50 and 11.67 mm). Structural activity relationships of the series suggest that the nature and location of the nitrogen substituents in the juglone scaffold, likely due in part to their redox potential, may influence the antibacterial activity of the series.
Prevalence of Prediabetes, Diabetes, and Its Associated Risk Factors among Males in Saudi Arabia: A Population-Based Survey
Authors: Aldossari Khaled K. , Aldiab Abdulrahman , Al-Zahrani Jamaan M. , Al-Ghamdi Sameer H. , Abdelrazik Mohammed , Batais Mohammed Ali , Javad Sundas , Nooruddin Shanila , Razzak Hira Abdul , El-Metwally Ashraf
Published: April 2018

Objectives. The study aims at determining the prevalence of prediabetes and diabetes and at ascertaining some concomitant risk factors among males in Saudi Arabia. Methods. A population-based cross-sectional study including 381 Saudi adult males from different institutions was recruited. Odds ratios for diabetes risk and risk factors were calculated using log-binomial and multinomial logistic regression, using STATA version 12. Results. The participants included 381 diabetic males with a median age of 45 years, average body mass index of 25 ± 40 kg/m2, whereas waist circumferences ranged from 66 to 180 cm in the male study population. In addition, 27.82% had normal BMI, 32.28% were overweight, and 36.22% were obese. Around 36% had higher waist circumference, that is, >102 cm. Age, BMI, marital status, and educational attainment were statistically significant predictors for prediabetes and diabetes. Conclusion. This study found that the prevalence of diabetes and prediabetes was 9.2% and 27.6%, respectively, for male Al-Kharj study population. The factors that increase the risk of diabetes and prediabetes include older age, obesity and overweight, being married, smoker, and having a civilian job and less education. All these factors were found statistically significant except smoking status and job type. In order to evaluate the causal relationship of these factors, prospective studies are required in future.
A Survey on Security-Aware Measurement in SDN
Authors: Zhang Heng , Cai Zhiping , Liu Qiang , Xiao Qingjun , Li Yangyang , Cheang Chak Fone
Published: April 2018

Software-defined networking (SDN) is one of the most prevailing networking paradigms in current and next-generation networks. Basically, the highly featured separation of control and data planes makes SDN a proper solution towards many practical problems that challenge legacy networks, for example, energy efficiency, dynamic network configuration, agile network measurement, and flexible network deployment. Although the SDN and its applications have been extensively studied for several years, the research of SDN security is still in its infancy. Typically, the SDN suffers from architecture defect and OpenFlow protocol loopholes such as single controller problem, deficiency of communication verification, and network resources constraint. Hence, network measurement is a fundamental technique of protecting SDN against the above security threats. Specifically, network measurement aims to understand and quantify a variety of network behaviors to facilitate network management and monitoring, anomaly detection, network troubleshooting, and the establishment of security mechanisms. In this paper, we present a systematic survey on security-aware measurement technology in SDN. In particular, we first review the basic architecture of SDN and corresponding security challenges. Then, we investigate two performance measurement techniques in SDN, namely, link latency and available bandwidth measurements. After that, we further provide a general overview of topology measurement in SDN including intradomain and interdomain topology discovering techniques. Finally, we list three interesting future directions of security-aware measurement in SDN followed by giving conclusion remarks.
GPU-Based Computation of Formation Pressure for Multistage Hydraulically Fractured Horizontal Wells in Tight Oil and Gas Reservoirs
Authors: Yin Rongwang , Li Qingyu , Li Peichao , Guo Yang , An Yurong , Lu Detang
Published: April 2018

A mathematical model for multistage hydraulically fractured horizontal wells (MFHWs) in tight oil and gas reservoirs was derived by considering the variations in the permeability and porosity of tight oil and gas reservoirs that depend on formation pressure and mixed fluid properties and introducing the pseudo-pressure; analytical solutions were presented using the Newman superposition principle. The CPU-GPU asynchronous computing model was designed based on the CUDA platform, and the analytic solution was decomposed into infinite summation and integral forms for parallel computation. Implementation of this algorithm on an Intel i5 4590 CPU and NVIDIA GT 730 GPU demonstrates that computation speed increased by almost 80 times, which meets the requirement for real-time calculation of the formation pressure of MFHWs.
Privacy‐Aware Multidimensional Mobile Service Quality Prediction and Recommendation in Distributed Fog Environment
Authors: Gong Wenwen , Qi Lianyong , Xu Yanwei
Published: April 2018

With the ever‐increasing popularity of mobile computing technology, a wide range of computational resources or services (e.g., movies, food, and places of interest) are migrating to the mobile infrastructure or devices (e.g., mobile phones, PDA, and smart watches), imposing heavy burdens on the service selection decisions of users. In this situation, service recommendation has become one of the promising ways to alleviate such burdens. In general, the service usage data used to make service recommendation are produced by various mobile devices and collected by distributed edge platforms, which leads to potential leakage of user privacy during the subsequent cross‐platform data collaboration and service recommendation process. Locality‐Sensitive Hashing (LSH) technique has recently been introduced to realize the privacy‐preserving distributed service recommendation. However, existing LSH‐based recommendation approaches often consider only one quality dimension of services, without considering the multidimensional recommendation scenarios that are more complex but more common. In view of this drawback, we improve the traditional LSH and put forward a novel LSH‐based service recommendation approach named SerRecmulti-qos, to protect users’ privacy over multiple quality dimensions during the distributed mobile service recommendation process.
Cutaneous Basal Cell Carcinoma with Lymph Node and Pulmonary Metastases
Authors: Wahl Renate U. , Cacchi Claudio , Rübben Albert
Published: April 2018

Basal cell carcinoma (BCC) is the most common skin cancer. Metastatic BCC is an extraordinary rare finding observed in only 0.5% of all cases. Until the introduction of the small molecule hedgehog inhibitor vismodegib, patients with metastatic BCC were treated with chemotherapy, most frequently platinum-based with mixed responses to therapy. We present the case of a 55-year-old Caucasian man who suffered from BCC on his left arm with lymph node and pulmonary metastases. Sonic hedgehog blockade with vismodegib only induced a short remission, and the patient succumbed to the cancer.
Stochastic Responses of Lightly Nonlinear Vibroimpact System with Inelastic Impact Subjected to External Poisson White Noise Excitation
Authors: Yang Guidong , Xu Wei , Huang Dongmei , Hao Mengli
Published: April 2018

A procedure for analyzing stationary responses of lightly nonlinear vibroimpact system with inelastic impact subjected to external Poisson white noise excitation is proposed. First, the original vibroimpact system is transformed to a new system without velocity jump in terms of the Zhuravlev nonsmooth coordinate transformation and the Dirac delta function. Second, the averaged generalized Fokker-Planck-Kolmogorov (FPK) equation for transformed system under parametric excitation of Poisson white noise is derived by stochastic averaging method. Third, the averaged generalized FPK equation is solved by using the perturbation technique and inverse transformation of the Zhuravlev nonsmooth coordinate transformation to obtain the approximately stationary solutions for response probability density functions of original vibroimpact system. Last, analytical and numerical results for two typical lightly nonlinear vibroimpact systems are presented to assess the effectiveness of the proposed method. It is found that they are in good agreement and the proposed method is quite effective.
Gene Expression Profiling in Behcet’s Disease Indicates an Autoimmune Component in the Pathogenesis of the Disease and Opens New Avenues for Targeted Therapy
Authors: Puccetti Antonio , Fiore Piera Filomena , Pelosi Andrea , Tinazzi Elisa , Patuzzo Giuseppe , Argentino Giuseppe , Moretta Francesca , Lunardi Claudio , Dolcino Marzia
Published: April 2018

Behçet disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. Disease etiopathogenesis is still unclear. We aim to elucidate some aspects of BD pathogenesis and to identify specific gene signatures in peripheral blood cells (PBCs) of patients with active disease using novel gene expression and network analysis. 179 genes were modulated in 10 PBCs of BD patients when compared to 10 healthy donors. Among differentially expressed genes the top enriched gene function was immune response, characterized by upregulation of Th17-related genes and type I interferon- (IFN-) inducible genes. Th17 polarization was confirmed by FACS analysis. The transcriptome identified gene classes (vascular damage, blood coagulation, and inflammation) involved in the pathogenesis of the typical features of BD. Following network analysis, the resulting interactome showed 5 highly connected regions (clusters) enriched in T and B cell activation pathways and 2 clusters enriched in type I IFN, JAK/STAT, and TLR signaling pathways, all implicated in autoimmune diseases. We report here the first combined analysis of the transcriptome and interactome in PBCs of BD patients in the active stage of disease. This approach generates useful insights in disease pathogenesis and suggests an autoimmune component in the origin of BD.
Design of Low-Complexity Hybrid Precoder and Inkjet-Printed Antenna Array for Massive MIMO Downlink Systems
Authors: D Subitha , J M Mathana
Published: April 2018

The dramatically growing mobile communication industry necessitates the demand for the speedy and error-free connectivity at considerably low cost for the billions of users. This is made possible only through the technological advancements that replace the current 4G wireless systems by 5G. Massive MIMO is the key technology used in 5G that offers spectral efficiency of up to 3 times and throughput of up to 10 times the current 4G. The additional antennas used in massive MIMO systems help in many ways but lack in complexity. Hence, in this paper, we propose two design methodologies to reduce the complexity of massive MIMO systems. The first one is the design of low-complexity hybrid precoder based on Zero-Forcing (ZF) precoding algorithm and Neumann series approximation. The second one is the design of flexible, environment friendly, simple 128-element antenna array at the frequency of 2.4 GHz using inkjet printing technology. The substrate used for printing is the “glossy paper” with dielectric constant of 2.31, and the ink used is silver nanoparticle ink with conductivity of 35,700,000 s/m. The element used for the formation of array is the z-shaped coplanar waveguide (CPW) monopole antenna. The performance of the proposed designs is evaluated in terms of probability of error for the hybrid precoding algorithm and radiation characteristics like gain, directivity, and return loss for the printed antenna design.
Plantar Stress-Related Injuries in Male Basketball Players: Variations on Plantar Loads during Different Maximum-Effort Maneuvers
Authors: Chen Yiyang , Li Jing Xian , Hong Youlian , Wang Lin
Published: April 2018

This study aims to compare the insole load of three maximum-effort cutting tasks in basketball. Sixteen male basketball players were recruited to participate in the study. The Pedar Mobile system was used to record the insole plantar load distribution during three cutting tasks (45° cutting, 90° cutting, and sideward cutting). The peak pressures (PP) and maximum force (MF) at the total foot and at each foot mask were used in data analysis. ANOVA with repeated measures was employed to investigate the differences in the measures among these cutting tasks. At the total foot, the highest MF value was showed when performing sideward cutting. At the heel, the highest PP and MF were found when performing 90° cutting. The PP and MF were lower when performing 90° cutting than when conducting 45° and sideward cuttings at the medial midfoot and the central forefoot. Furthermore, the MF value was lower when performing 45° cutting than when conducting sideward cutting at the medial midfoot and the central forefoot. These findings corroborate the fact that plantar loads differed during the three maximum-effort cutting maneuvers. Differences in the plantar loads for different cutting may be potential risks for overuse-related injuries to the lower extremities of basketball players.
A General Purpose Adaptive Fault Detection and Diagnosis Scheme for Information Systems with Superheterodyne Receivers
Authors: Song Dengwei , Liu Hongmei , Qi Le , Zhou Bo
Published: April 2018

A superheterodyne receiver is a type of device universally used in a variety of electronics and information systems. Fault detection and diagnosis for superheterodyne receivers are therefore of critical importance, especially in noise environments. A general purpose fault detection and diagnosis scheme based on observers and residual error analysis was proposed in this study. In the scheme, two generalized regression neural networks (GRNNs) are utilized for fault detection, with one as an observer and the other as an adaptive threshold generator; faults are detected by comparing the residual error and the threshold. Then, time and frequency domain features are extracted from the residual error for diagnosis. A probabilistic neural network (PNN) acts as a classifier to realize the fault diagnosis. Finally, to mimic electromagnetic environments with noise interference, simulation model under different fault conditions with noise interferences is established to test the effectiveness and robustness of the proposed fault detection and diagnosis scheme. Results of the simulation experiments proved that the presented method is effective and robust in simulated electromagnetic environments.
Integrated Modeling, Simulation, and Visualization for Nanomaterials
Authors: Qin Feiwei , Xia Haibin , Peng Yong , Wu Zizhao
Published: April 2018

Computer aided modeling and simulation of nanomaterials can describe the correlation between the material’s microstructure and its macroscopic properties quantitatively. In this paper, we propose an integrated modeling, simulation, and visualization approach for designing nanomaterials. Firstly, a fast parametric modeling method for important nanomaterials such as graphene, nanotubes, and MOFs is proposed; secondly, the material model could be edited adaptively without affecting the validity of the model on the physical level; thirdly a preliminary calculation for nanomaterials’ energy is implemented based on the theory of surface fitting; finally, an integrated framework of nanomaterials modeling, simulation, and visualization is designed and implemented. Experimental results show that the proposed approach is feasible and effective.
An Effective Pt-Cu/SiO2 Catalyst for the Selective Hydrogenation of Cinnamaldehyde
Authors: Wang Dong , Zhu Yujun
Published: April 2018

The bimetal catalyst Pt-Cu/SiO2 was prepared by the impregnation method. Its catalytic performance was investigated by the selective hydrogenation of cinnamaldehyde. Pt-Cu/SiO2 exhibited much higher selectivity (64.1%) to cinnamyl alcohol than Pt/SiO2 (3.7%), while they showed similar conversion of cinnamaldehyde. This enhancement was attributed to the increase in the amount of the Pt0 species on the Pt-Cu/SiO2 surface, which is derived from the interaction between Pt and Cu revealed by XRD and XPS.
Postradiation Histiocytic Sarcoma in the Setting of Muir-Torre Syndrome
Authors: Baumgartner Erin , Ullman David , Jones Jeffrey Adam , Fasciano Danielle , Atherton Daniel S. , Pavlidakey Peter , Peker Deniz
Published: April 2018

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant genetic disorder characterized by a predisposition towards colorectal carcinoma and other extracolonic neoplasms. Histiocytic sarcoma (HS) is a very rare hematologic neoplasm characterized by a malignant proliferation of cells with histiocytic differentiation. We present the case of a 62-year-old male with previous diagnosis of MTS who presented with metastatic colorectal adenocarcinoma, bilateral papillary renal cell carcinoma, and a new squamous cell carcinoma of the scalp, treated with resection and adjuvant radiation therapy. After reconstructive surgery for his scalp resection, the patient developed a persistent nonhealing skin defect. A punch biopsy of this nonhealing skin defect and subsequent immunohistochemistry revealed neoplastic histiocytic cells restricted to the epidermis and underlying dermis. The diagnosis of cutaneous histiocytic sarcoma was then rendered. Histiocytic sarcoma is an exceptionally rare malignancy. Consequently, there is no universally agreed upon management protocol for this malignancy. The patient was admitted to hospice and treated with palliative radiation. This case demonstrates the need for awareness of the risk of secondary malignancies in cancer patients in order to facilitate early surgical intervention and optimal treatment.
Shexiang Baoxin Pills as an Adjuvant Treatment for Chronic Heart Failure: A System Review and Meta‐Analysis
Authors: Dong Taiwei , Wang Jian , Ma Xiao , Ma Rong , Wen Jianxia , Chen Nian , Xie Qian
Published: April 2018

Background. Shexiang Baoxin pills (SXBXP), as a Traditional Chinese Medicine, are widely used for chronic heart failure in China. It is essential to systematically assess the efficacy and safety of SXBXP as an adjuvant treatment for chronic heart failure. Methods. Seven English and Chinese electronic databases (PubMed, Embase, Cochrane Library, CBM, Wanfang, VMIS, and CNKI) were searched from inception to July 2017. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Meta‐analysis was performed by Review Manager 5.3. Results. A total of 27 RCTs with 2637 participants were included in this review. Compared to conventional treatment, SXBXP combined with conventional treatment showed potent efficacy when it came to the total efficacy rate (OR, 3.88; 95% CI, 2.87, 5.26; P < 0.00001), B‐type natriuretic peptide (BNP) (MD = −66.95; 95% CI, −108.57, −25.34; P = 0.002), N‐terminal pro‐brain natriuretic peptide (NT‐ProBNP) (MD = −0.15; 95% CI, −0.21, −0.09; P < 0.00001), six‐minute walking distance (6‐MWD) (MD = 38.57; 95% CI, 28.47, 48.67; P < 0.00001), cardiac output (CO) (MD = 0.84; 95% CI, 0.68, 0.99; P < 0.00001), and Stroke Volume (SV) (MD = 7.43; 95% CI, 4.42, 10.44, P < 0.00001). The pooled subgroup analysis indicated that there was a significant difference between SXBXP plus conventional treatment and conventional treatment alone in short term course (OR = 3.51; 95% CI, 2.28, 5.40; P < 0.00001), in middle period of treatment (OR = 5.01; 95% CI, 2.61, 9.60; P < 0.00001), and in long‐term course (OR = 3.77; 95% CI, 2.13, 6.67; P < 0.00001). No serious adverse events or reactions were mentioned in these RCTs. Conclusions. As an adjuvant drug, this study suggested that SXBXP provide an obvious efficacy for the treatment of CHF. However, due to small samples and generally low quality studies being applied in this study, more rigorous and well‐designed RCTs are needed to confirm these findings.
TheYABBYGenes of Leaf and Leaf-Like Organ Polarity in Leafless PlantMonotropa hypopitys
Authors: Shchennikova Anna V. , Slugina Marya A. , Beletsky Alexey V. , Filyushin Mikhail A. , Mardanov Andrey A. , Shulga Olga A. , Kochieva Elena Z. , Ravin Nikolay V. , Skryabin Konstantin G.
Published: April 2018

Monotropa hypopitysis a mycoheterotrophic, nonphotosynthetic plant acquiring nutrients from the roots of autotrophic trees through mycorrhizal symbiosis, and, similar to other extant plants, forming asymmetrical lateral organs during development. The members of the YABBY family of transcription factors are important players in the establishment of leaf and leaf-like organ polarity in plants. This is the first report on the identification ofYABBYgenes in a mycoheterotrophic plant devoid of aboveground vegetative organs. SevenM. hypopitys YABBYmembers were identified and classified into four clades. By structural analysis of putative encoded proteins, we confirmed the presence of YABBY-defining conserved domains and identified novel clade-specific motifs. Transcriptomic and qRT-PCR analyses of different tissues revealedMhyYABBYtranscriptional patterns, which were similar to those of orthologousYABBYgenes from other angiosperms. These data should contribute to the understanding of the role of theYABBYgenes in the regulation of developmental and physiological processes in achlorophyllous leafless plants.
An Empirical Research on Marketing Strategies of Different Risk Preference Merchant
Authors: Chen Quan , Wang Jiangtao , Yu Jianjun , Tsai Sang-Bing
Published: April 2018

Holiday merchandise has unique demand characteristics, unofficial start data, and a limited life cycle. In an intensely competitive market, individual merchants are able to get more sales opportunities if they display their products earlier. In this study, a time-variant variance and time-variant expected market demand model are introduced to investigate the order strategies that are used by risk-averse holiday merchants. Our results show that risk preference, market uncertainty, and market power have a significant effect on the merchant’s market strategies. Risk-averse merchants prefer to enhance forecast accuracy rather than using an early-display advantage. They can even give up their early-display advantage if they are faced with increased market uncertainty and small market power. Compared with the fixed purchase cost, the time-sensitive purchase cost can stimulate the merchant to purchase in advance, but this can decrease the merchant’s profit. Consequently, risk-averse merchants always display their merchandise later, decrease the order quantity, and, finally, miss the market opportunity.
Non-Darcy Flow Experiments of Water Seepage through Rough-Walled Rock Fractures
Authors: Ni Xiao-dong , Niu Yu-long , Wang Yuan , Yu Ke
Published: April 2018

The knowledge of flow phenomena in fractured rocks is very important for groundwater-resources management in hydrogeological engineering. The most commonly used tool to approximate the non-Darcy behavior of the flow velocity is the well-known Forchheimer equation, deploying the “inertial” coefficient β that can be estimated experimentally. Unfortunately, the factor of roughness is imperfectly considered in the literature. In order to do this, we designed and manufactured a seepage apparatus that can provide different roughness and aperture in the test; the rough fracture surface is established combining JRC and 3D printing technology. A series of hydraulic tests covering various flows were performed. Experimental data suggest that Forchheimer coefficients are to some extent affected by roughness and aperture. At last, favorable semiempirical Forchheimer equation which can consider fracture aperture and roughness was firstly derived. It is believed that such studies will be quite useful in identifying the limits of applicability of the well-known “cubic law,” in further improving theoretical/numerical models associated with fluid flow through a rough fracture.
Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice
Authors: Hong Pu , Li Feng-Xian , Gu Ruo-Nan , Fang Ying-Ying , Lai Lu-Ying , Wang Yong-Wei , Tao Tao , Xu Shi-Yuan , You Zhi-Jian , Zhang Hong-Fei
Published: April 2018

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.
Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study
Authors: Shah Manish A. , Starodub Alexander , Sharma Sunil , Berlin Jordan , Patel Manish , Wainberg Zev A. , Chaves Jorge , Gordon Michael , Windsor Kevin , Brachmann Carrie Baker , Huang Xi , Vosganian Greg , Maltzman Julia D. , Smith Victoria , Silverman Jeffrey A. , Lenz Heinz-Josef , Bendell Johanna C.
Published: April 2018

Purpose: Matrix metalloproteinase-9 (MMP9) is implicated in protumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6.

Patients and Methods: Three dosages of andecaliximab monotherapy [200, 600, and 1800 mg i.v. every 2 weeks (q2w)] were investigated in patients with advanced solid tumors (n = 13 in a 3+3 design). After determining a recommended dose, patients with advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma (n = 40) received 800 mg andecaliximab + mFOLFOX6 q2w. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed.

Results: Andecaliximab monotherapy demonstrated no dose-limiting toxicity (DLT) in any cohort, displaying target-mediated drug disposition at the lowest dose (200 mg) and linear pharmacokinetics at higher doses. Based on target engagement, recommended doses for further study are 800 mg q2w or 1,200 mg q3w. Maximal andecaliximab target binding, defined as undetectable andecaliximab-free MMP9 in plasma, was observed in the gastric/GEJ adenocarcinoma cohort. We observed no unusual toxicity, although there were four deaths on study not attributed to andecaliximab treatment. In first-line patients (n = 36), median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI), 5–13.9 months], and the overall response rate (ORR) was 50%. Among all patients (n = 40), median PFS was 7.8 (90% CI, 5.5–13.9) months, and ORR was 48%, with a median duration of response of 8.4 months.

Conclusions: Andecaliximab monotherapy achieved target engagement without DLT. Andecaliximab + mFOLFOX6 showed encouraging clinical activity without additional toxicity in patients with HER2-negative gastric/GEJ adenocarcinoma. A phase III study evaluating mFOLFOX6 ± andecaliximab in this setting is ongoing. Clin Cancer Res; 24(16); 3829–37. ©2018 AACR.
Drug-Induced Senescent Multiple Myeloma Cells Elicit NK Cell Proliferation by Direct or Exosome-Mediated IL15 Trans-Presentation
Authors: Borrelli Cristiana , Ricci Biancamaria , Vulpis Elisabetta , Fionda Cinzia , Ricciardi Maria Rosaria , Petrucci Maria Teresa , Masuelli Laura , Peri Agnese , Cippitelli Marco , Zingoni Alessandra , Santoni Angela , Soriani Alessandra
Published: April 2018

Treatment of multiple myeloma (MM) cells with sublethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein, we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 upregulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells from patients’ bone marrow (BM) aspirates. However, IL15 was detectable as a soluble cytokine only in vivo, thus indicating a functional role of IL15 in the BM tumor microenvironment. The increased IL15 was accompanied by enhanced expression of the IL15/IL15RA complex on the membrane of senescent myeloma cells, allowing the functional trans-presentation of this cytokine to neighboring NK cells, which consequently underwent activation and proliferation. We demonstrated that MM cell–derived exosomes, the release of which was augmented by melphalan treatment in senescent cells, also expressed IL15RA and IL15, and their interaction with NK cells in the presence of exogenous IL15 resulted in increased proliferation. Altogether, our data demonstrated that low doses of chemotherapeutic drugs, by inducing tumor cell senescence and a senescence-associated secretory phenotype, promoted IL15 trans-presentation to NK cells and, in turn, their activation and proliferation, thus enhancing NK cell–tumor immune surveillance and providing new insights for the exploitation of senescence-based cancer therapies. Cancer Immunol Res; 6(7); 860–9. ©2018 AACR.
Effect of Meal Ingestion on Liver Stiffness and Controlled Attenuation Parameter
Authors: Silva Marco , Costa Moreira Pedro , Peixoto Armando , Santos Ana Luísa , Lopes Susana , Gonçalves Regina , Pereira Pedro , Cardoso Hélder , Macedo Guilherme
Published: April 2018

Background and Aims: Despite the increasing use of noninvasive methods for the assessment of liver fibrosis and steatosis, the effect of fasting and food intake on these parameters is not yet clear. Our aims were to evaluate the effect of food intake on liver stiffness (LS) (measured by transient elastography) and controlled attenuation parameter (CAP) in patients with different degrees of liver disease and healthy volunteers, and secondarily, to assess possible factors associated with variations of LS and CAP. Methods: We performed a prospective single-center study including patients with liver disease and healthy volunteers. LS and CAP were evaluated using FibroScan® (Echosens, Paris, France), before (fasting ≥8 h) and 30 min after intake of a standardized breakfast. We used common cutoffs for LS: > 7 kPa for significant fibrosis (F2 to F4) and > 11 to 14 kPa (mean 12.5 kPa) for cirrhosis. Results: Fifty-nine (72%) patients with liver disease and 22 (28%) healthy volunteers were included. LS significantly increased 30 min after food intake (pre-meal 6.1 kPa [IQR: 4.7–9.8] vs. after-meal 6.8 kPa [IQR: 5.5–10.6]; p < 0.001). This difference was only significant in patients with chronic liver disease (p = 0.02) and not in healthy volunteers (p = 0.106). CAP values did not increase significantly after food intake. Gender, body mass index, mass of body fat, lean body mass, and percent of body fat were not related with significant variations of LS and CAP values after meal intake. Conclusions: Significant variations of LS were observed after ingestion of a standard meal, which may have consequences for patient management. CAP values were not significantly affected by food intake. Therefore, we consider that before the isolated evaluation of CAP, it is not necessary to perform any fasting period.
Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes
Authors: Huang Zhouqing , Ye Bozhi , Wang Zhengxian , Han Jibo , Lin Lu , Shan Peiren , Cai Xueli , Huang Weijian
Published: April 2018

Backgrund/Aims: Ischemia reperfusion (I/R) promotes the severity of cardiomyocyte injury. Long noncoding RNAs (LncRNAs) are key regulators in cardiovascular diseases. However, the association between LncRNAs and myocardial I/R injury has not been thoroughly characterized to date. We attempted to clarify the potential biological role of a LncRNA (E230034O05Rik), which we named hypoxia/reoxygenation (H/R) injury-related factor in myocytes (HRIM), by investigating the differential expression of LncRNAs between groups of myocytes exposed to either a normal level of oxygen or to H/R. Methods: Microarray analysis was used to determine analyze the global differential expression of LncRNAs in H9c2 myocytes exposed either to a normal level of oxygen or to H/R. Target LncRNA levels were further verified in vitro and ex vivo by real-time polymerase chain reaction (qPCR). Cell viability was analyzed using the Cell Counting Kit-8 assay. Autophagy levels were confirmed by Western blotting, transmission electron microscopy, and autophagic double-labeled (mRFP-GFP-LC3) adenovirus analyses. Results: Gene expression profiling revealed that 797 LncRNAs and 1898 mRNAs were differentially expressed in the H/R group compared with the normal oxygen group. Among these LncRNAs and mRNAs, 6 upregulated LncRNAs and 2 downregulated LncRNAs in the H/R group were selected and further validated by qPCR in vitro and ex vivo. Additionally, LncRNA-HRIM was inhibited by specific siRNAs in H9c2 myocytes exposed to H/R. The inhibition of LncRNA-HRIM by siRNA prevented cell death by suppressing excessive autophagic activity in myocytes, This finding suggests a detrimental role of LncRNA-HRIM in the regulation of I/R injury. Conclusions: LncRNAs are involved in H/R injury of H9c2 myocytes. Inhibition of LncRNA-HRIM increased cell viability by reducing autophagy in myocytes during H/R.
Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies
Authors: Wu Shuiqing , Zhao Xiaokun , Wang Yinhuai , Zhong Zhaohui , Zhang Lei , Cao Jian , Ai Kai , Xu Ran
Published: April 2018

Background/Aims: Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. Methods: The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. Results: The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. Conclusions: our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients.
ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia
Authors: Liu Cheng-cheng , Wang Hua , Wang Wei-da , Wang Liang , Liu Wen-jian , Wang Jing-hua , Geng Qi-rong , Lu Yue
Published: April 2018

Background/Aims: The metabolic features of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. The expression of glycolytic enzyme enolase 2 (ENO2) was found to be closely associated with the clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions remain unclear in ALL. Methods: We evaluated the association between ENO2 mRNA expression in bone marrow mononuclear cells (BM-MNCs) and the efficacy of chemotherapy, and further explored the function of ENO2 in ALL. The molecular mechanisms of ENO2 expression and its effects on cell growth, glycolysis and glucocorticoid resistance were explored by Cell Counting Kit-8, glucose-consumption assay, Quantitative RT-PCR, Western blotting and in vivo tumorigenesis in NOD/SCID mice. Results: The results showed that ENO2 mRNA expression in BM-MNCs was significantly decreased when patients completed induction chemotherapy and reached complete remission (CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional studies demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further studies revealed that ENO2 up-regulated various glycolysis-related genes and enhanced Akt activity with subsequent glycogen synthase kinase3β (GSK-3β) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival. Conclusions: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL.
A fragmentação do Direito Internacional: entre o discurso e a realidade do sistema jurídico internacional
Authors: Capucio Camilla
Published: April 2018

O artigo objetiva analisar criticamente o discurso da fragmentação do Direito Internacional por meio de uma análise detalhada dos documentos da Comissão de Direito Internacional da ONU, verificando suas diferenças e inconsistências. A partir da crítica desta perspectiva que vislumbra na expansão do Direito Internacional motivos para o seu enfraquecimento, o trabalho destaca a visão sistêmica do Direito Internacional e sua relevância para o sistema jurídico contemporâneo. Embora a teoria da fragmentação seja base para diversos trabalhos acadêmicos na atualidade, faz-se relevante e necessário um exame detido sobre as diferentes nuances dos próprios documentos da Comissão que difundiram tal discurso, e por isso o trabalho se justifica. Adicionalmente, a atividade dos tribunais internacionais pode se dar de modo a harmonizar o sistema jurídico internacional e reforçar o papel do Direito Internacional como um instrumento universal.
A conformação constitucional do novo regime brasileiro de tributação offshore: um estudo da Lei n. 12.973/2014
Authors: Silva Brenno Birckholz da
Published: April 2018

A recém-aprovada sistemática de CFC rules brasileira suscita duas importantes indagações: (i) a nova legislação é (ou não) conforme aos princípios econômicos do texto constitucional?; e (ii) quais os efeitos desse regramento na internacionalização produtiva de empresas nacionais, bem como sobre a competitividade de pessoas jurídicas controladas e/ou coligadas àquelas? O objetivo final é a aferição de possível relação de causalidade entre a tributação adotada pelo país e sua potencial contribuição ao desenvolvimento econômico-produtivo nacional, sem prejuízo do interesse orçamentário e de coibir a evasão fiscal. Tomadas essas premissas, o grande desafio orienta-se à construção de um ponto ótimo de inflexão tributária, elaborando uma norma world wide income taxation que proteja a arrecadação, mas que ao mesmo tempo não inviabilize as empresas brasileiras de competir no mercado internacional globalizado.
Society in Qatar before the Oil Industry in Light of Archaeological Evidence
Authors: Sadeq Moain
Published: April 2018

The archaeological excavations conducted within Qatar have revealed remains of a series of towns and villages dated to the pre-oil industrial era, particularly from the 18th to the beginning of the 20th centuries (Guérin & al-Na‘imi 2008; Hardy-Guilbert 1998). Particularly important sources for our study are the major archaeological site of al-Zubarah, which was inscribed in the unesco World Heritage sites in 2013, and the site of Ra’s ‘Ushayrig and its adjacent human settlements, such as al-Ruwaydah and al-Burayqa. The archaeological record of the uncovered architecture and material culture (e.g., vessels and tools) is a primary source for understanding and reconstructing Qatar micro history and communal identity of Qatar during this period. In light of archaeological evidence, this paper endeavors to discuss the characteristics of the Qatari communal identity before the oil industrial era, focusing particularly on the period from the 18th to the beginning of the 20th century.
Review of the genus Engyprosopon Günther, 1862 (Pleuronectiformes: Bothidae) from waters off Taiwan, with descriptions of two new species
Authors: AMAOKA KUNIO , HO HSUAN-CHING
Published: April 2018

Species of the bothid genus Engyprosopon Günther, 1862 from the waters off Taiwan are reviewed. Nine species are recognized and described. Of the nine species, E. grandisquama (Temminck & Schlegel, 1846), E. multisquama Amaoka, 1963 and E. maldivense (Regan, 1908) previously known from Taiwan are confirmed, whereas E. xystrias Hubbs, 1915, E. mogkii (Bleeker, 1854), E. longipelvis Amaoka, 1969 and E. mozambiquense Hensley, 2003 represent new records for Taiwan. Moreover, two further species are described new to science. Engyprosopon brevifrontale sp. nov. is characterized by a deep and short body, large eyes situated close to the head margin, 0 + 9–10 smooth gill rakers, strong rostral and upper orbital spines on the ocular side, small rostral spine on the blind side, and a dark blue peritoneum. Engyprosopon parvipectorale sp. nov. is characterized by the combination of serrate gill rakers, large head (3.1–3.4 in SL); extremely narrow or almost ridge-like interorbital in both sexes; ocular-side pectoral fin distinctly short (1.4–1.6 in HL) in both sexes; and no rostral or orbital spines in either sex. Detailed descriptions and a key to all of the species of Engyprosopon recorded from the waters off Taiwan are provided.
A new genus and species of subfamily Banchinae (Hymenoptera, Ichneumonidae) from China
Authors: SHENG MAO-LING , SUN SHU-PING , WANG XI-NAN , WU HAI-WEI
Published: April 2018

A new genus, Verruca Sheng & Sun gen. nov., of the ichneumonid tribe Atrophini, subfamily Banchinae is described for one new species, Verruca dentia Sheng & Sun, sp. nov. The species was collected from Shandong and Jiangxi Provinces, situated near the northern border of the Oriental part of China. The new genus is placed within the existing key to genera. A key to the genera of Atrophini, with the apical portion of the ovipositor with ridges, is also provided.
Simulation Experiments for Meteorological Observing Systems for GARP1
Authors: Kasahara Akira
Published: April 2018

The future observing system of the global atmosphere which has been contemplated for the Global Atmospheric Research Program (GARP) is a combination of various observing subsystems including satellites, constant-level balloons, automatic ocean buoys, etc., as well as conventional upper-air and surface networks. All observing subsystems are neither perfect nor ideal. Numerical experiments (with global circulation models) are needed to evaluate the subsystems in terms of the accuracy, density, and frequency of observations. They are called Observing Systems Simulation Experiments (OSSE).

The purpose of this report is to describe the present activities in OSSE. Most useful up-to-date information was obtained from the oral presentation of papers at the International Symposium on Four-Dimensional Data Assimilation, Princeton, N. J., 19–22 April 1971.

Since a global circulation model is used as an integrator and analyzer of observed data in three-dimensional space and time taken from various observing subsystems, the question of error growth of the prediction model in relation to the accuracy of observation is discussed as the predictability experiment.

Another important property of the model atmosphere is the ability to adjust the model's variables for forced prescription of incomplete observed data. This adjustment property is used to assimilate observed data in four dimensions. The method of direct substitution is used to determine the basic data requirements for observation of wind, temperature, and surface pressure.

Various methods of four-dimensional data assimilation are reviewed for the purpose of optimum design for OSSE. Finally, questions concerning the reference level information are reviewed and results of some numerical experiments conducted at the National Center for Atmospheric Research are presented.
Problems of Large-Scale Kinetic Energy Balance—A Diagnostic Analysis in GARP
Authors: Kung Ernest C. , Smith Phillip J.
Published: April 2018

Currently available diagnostic studies on kinetic energy balance in the general circulation are reviewed as one of the basic scientific problems in GARP.

The kinetic energy equation and several different approaches in the evaluation of energy variables are discussed in relation to real and modeled atmospheric data. Energy balance problems in the middle latitudes are examined in terms of linkages between processes from energy conversion to dissipation, balance within various systems of circulation, and interactions with sub-synoptic scale disturbances. The kinetic energy budget in large-scale disturbances and the general flow of the tropical circulation are contrasted with those in the middle latitudes.

By clarifying the current essential problems in the energetics of the middle latitudes and tropics, ongoing diagnostic studies at the University of Missouri—Columbia and Purdue University are identified in the context of the GARP.
Commercial Aircraft as a Source of Automated Meteorological Data for GATE and DST
Authors: Julian Paul R. , Steinberg Robert
Published: April 2018

Specially-equipped wide-body commercial aircraft which are flying tropical and Southern Hemispheric routes are providing a new and unique source of meteorological data with a 100 km spatial resolution. Data have been gathered for the GATE, and the planning for a similar effort for the DST is in progress. These aircraft not only provide synoptic data in critical areas devoid of conventional data, but are, in effect, meteorological research platforms that can provide valuable information on mesoscale phenomena. By 1976 it is anticipated that there will be over 80 such aircraft flying global routes. These specially-equipped jets could also be effectively used for FGGE by providing the nucleus of a supplementary observing system for gathering world-wide meteorological data.