bluuebunny/crossref_metadata_2025 huggingface dataset:
The studies on the physical and dissociation properties of chlorobenzene under external electric fields
Authors: Lin Hua , Liu Yuzhu , Yin Wenyi , Yan Yihui , Ma Luwei , Jin Yaru , Qu Yingfei , Abulimiti Bumaliya
Published: May 2018

Chlorobenzene is one of the Persistent Organic Pollutants (POPs) threatening human health. It is significant to study the degradation mechanism under external electric fields. Based on the density functional theory, the physical and dissociation properties including C–Cl bond length, total energy, dipole moment, frontier orbital energy, energy gap, IR spectrum, UV-vis absorption spectrum and potential energy curve are studied under external electric fields. According to these results, it is found that the C–Cl bond length becomes longer and tends to break with the increase of external electric field and the energy gap decreases with the increase of positive as well as negative external electric field. Moreover, the dissociation barrier in potential energy curve decreases and equilibrium bond length increases with increase of positive external electric field. And when external electric field reaches 0.040 atomic units ([Formula: see text], 1 atomic [Formula: see text], the dissociation barrier disappears which means that degradation of chlorobenzene occurs under strong external electric field due to the breakage of C–Cl bond. These results provide important references for studying the degradation mechanism of chlorobenzene under strong external electric fields.
A small molecular boron-phenylpyrrin sensor for H+/Fe3+ and its application as a digital demultiplexer
Authors: Yao Yiwei , Wang Fang , Zhang Xiuling , Wang Dunqing , Song Lingyun , Zhang Yu , Liu Leifang , Chen Yuting
Published: May 2018

A julolidine-based boron-phenylpyrrin small molecule has been designed and synthesized through a one-pot condensation-complexation procedure. Systematic optical studies show that this compound displays two distinct optical responses to the addition of HCl and Fe[Formula: see text] in succession: the addition of HCl induces an obvious red shift in its maximum absorption and fluorescence emission bands accompanied with the fluorescence quenching, whereas after synchronously adding H[Formula: see text] and Fe[Formula: see text], the maximum absorption and fluorescence emission wavelength were found to shift little but with an obvious decrease in the absorbance and fluorescence intensity, suggesting the dual-detecting nature of this compound to H[Formula: see text] and Fe[Formula: see text] under acid conditions. More interestingly, based on the HCl/Fe[Formula: see text]-mediated absorption and fluorescence signal features, JBPP can function as AND, NAND, INH and IMP logic gates which can be further developed into a 2:4 digital demultiplexer These will endow this small molecule compound with great potential for applications in molecular logic material, chemosensors and biological fields.
One-step synthesis of spherical NaTaO3 and graphene spherical NaTaO3 nanoparticles with enhanced photocatalytic activity for NO purification
Authors: Ding Zimao , Guo Sheng , Wu Xiaoyong , Fida Hussain
Published: May 2018

To obtain efficient photocatalytic air purification, a series of NaTaO3 nanoparticles were successfully synthesized through a one-pot solvothermal approach, using water/glycerol mixed solution as solvent. The glycerol not only played an important role for controlling the morphology and particle size, but also remarkably enhanced the specific surface area of the as-prepared NaTaO3. Under optimal conditions, the spherical NaTaO3 (NaTaO3-30) exhibited much higher deNO[Formula: see text] performance under UV irradiation as compared to the cubic NaTaO3 (NaTaO3-0). Furthermore, the graphene spherical NaTaO3 composites were also prepared to further enhance the visible light driven photocatalytic ability of spherical NaTaO3. When 1[Formula: see text]wt.% graphene was loaded, the spherical NaTaO3/graphene showed excellent performance for continuous NO gas destruction under UV irradiation, short wavelength visible light ([Formula: see text][Formula: see text]nm) and even long wavelength visible light ([Formula: see text][Formula: see text]nm), which was superior to spherical NaTaO3 and cubic NaTaO3/graphene. The increased specific surface area, expanded light absorption and accelerated electron transport were responsible for the enhanced photocatalytic activity of the composite. The present work may shed new light on the synthesis of novel perovskite-type NaTaO3-based catalysts with excellent photocatalytic performance.
A Critical Review of the Prominent Method of Heat Transfer Enhancement for the Fin-and-Tube Heat Exchanger by Interrupted Fin Surface: The Vortex Generators Approach
Authors: Chimres Nares , Wongwises Somchai
Published: May 2018

The performance of heat exchangers impacts industry investment, energy consumption, and pollution because the heat exchanger has been used in many industries. The use of vortex generators on the fin is the prominent method of heat transfer enhancement because the performance indexes of fins with vortex generators are greater than those of the fins without vortex generators. However, this method faces obstacles because the concepts and design instructions are still obscure. Therefore, this paper provides a summary of the publications about the use of vortex generators. The publications on the effects of traditional and alternative vortex generators that are combined with plain, wavy, and louver fins are summarized. The aim of this paper is to aggregate the publications concerned with the thermal performance and flow characteristics of the fin-and-tube heat exchanger with vortex generator using numerical and experimental investigations as the guideline for future studies.
Visual Interactive Creation, Customization, and Analysis of Data Quality Metrics
Authors: Bors Christian , Gschwandtner Theresia , Kriglstein Simone , Miksch Silvia , Pohl Margit
Published: May 2018

During data preprocessing, analysts spend a significant part of their time and effort profiling the quality of the data along with cleansing and transforming the data for further analysis. While quality metrics—ranging from general to domain-specific measures—support assessment of the quality of a dataset, there are hardly any approaches to visually support the analyst in customizing and applying such metrics. Yet, visual approaches could facilitate users’ involvement in data quality assessment. We present
MetricDoc
, an interactive environment for assessing data quality that provides customizable, reusable quality metrics in combination with immediate visual feedback. Moreover, we provide an overview visualization of these quality metrics along with error visualizations that facilitate interactive navigation of the data to determine the causes of quality issues present in the data. In this article, we describe the architecture, design, and evaluation of
MetricDoc
, which underwent several design cycles, including heuristic evaluation and expert reviews as well as a focus group with data quality, human-computer interaction, and visual analytics experts.
The Activity Concentrations and Radium Equivalent Activity in Soil Samples Collected from the Eastern Part of Basrah Governorate in Southern Iraq
Authors: Ahmed Rasha S. , Mohammed Raghad S. , Abdaljalil Rana O.
Published: May 2018

Clay soil samples (0, 30, and 60 cm depths) were collected from two districts (Abu Al Khasib and Ad Dayr) in Basrah governorate in southern Iraq for gamma-ray spectroscopy. The activity concentrations for natural existing radionuclides in 18 soil samples were measured using high-purity germanium detector HPGe. From the obtained results of γ-ray spectroscopy, the 238U activity concentrations were found to be ranging from 2.4 to 5.6 ppm with an average of 3.5 ppm in Abu Al Khasib and ranging from 2.1 to 4.5 ppm with an average of 2.9 ppm in Ad Dayr. 232Th concentrations were ranging from 3.6 to 7.5 ppm with an average of 4.7 ppm in Abu Al Khasib and ranging from 3.7 to 7.9 ppm with an average of 5.0 ppm in Ad Dayr. 40K concentration was ranging from 0.1% to 2.0% with an average of 1.2% in Abu Al Khasib and ranging from 0.9% to 1.8% with an average of 1.3% in Ad Dayr. High 238U and 226Ra concentration levels were recorded in both study regions. The concentrations of 232Th are within the normal limits in both regions. High levels of 40K were recorded in some locations. Generally, in most locations, 40K activity was within normal ranges. The radium equivalent activity, the external hazard index, the internal hazard index, and the radioactivity level index were calculated to estimate the radiation hazard in Basrah. The estimated radiation hazard indices were within normal limits, except the radioactivity level index, which shows elevated values. The obtained results were compared with other countries and with the worldwide median certified values.
Antiangiogenic Herbal Composition Ob‐X Reduces Abdominal Visceral Fat in Humans: A Randomized, Double‐Blind, Placebo‐Controlled Study
Authors: Kang Jae-Heon , Jeong In Sun , Kim Min-Young
Published: May 2018

Adipose tissue growth is angiogenesis‐dependent, and angiogenesis inhibitors can regulate adipose tissue mass by cutting off the blood supply. We examined whether antiangiogenic herbal composition Ob‐X can reduce fast‐growing abdominal fat, especially visceral fat in humans by inhibiting angiogenesis. Eighty abdominally obese subjects (body mass index: 25‐29.9 kg/m2, waist circumference: exceeding 90 cm for males and 85 cm for females) participated in a 12‐week randomized, double‐blind, placebo‐controlled human study to evaluate the efficacy and safety of Ob‐X. 690 mg of Ob‐X was administered orally twice a day. The Ob‐X group showed a noticeable reduction in visceral fat of 20.5% after the 12‐week treatment as compared to baseline measured by computed tomography. The change in visceral fat in the Ob‐X group was statistically significant as compared to the placebo group (p = 0.0495) and 1.9 times higher than in the placebo group. Therefore, angiogenesis inhibitor Ob‐X has the potential to improve obesity‐related metabolic syndrome by reducing dangerous visceral fat.
Clinical and Biological Signature of Osteochondritis Dissecans in a Cross-Sectional Study
Authors: Gabusi Elena , Manferdini Cristina , Paolella Francesca , Gambari Laura , Kon Elizaveta , Filardo Giuseppe , Mariani Erminia , Lisignoli Gina
Published: May 2018

The healing potential of knee osteochondritis dissecans (OCD) focal lesions is not well defined. We performed a cross-sectional study correlating local and systemic biological characteristics with the patients’ characteristics. We evaluated both local tissue markers (CD34, CD146, CD166, and tartrate-resistant acid phosphatase (TRAP)) and systemic serum biomarkers (fragments or propeptide of type II collagen: C2C, CTX-II, CPII, and TRAP5b) on histologically scored osteochondral fragments or serum from OCD patients. These biological features were associated with the patients’ characteristics (IKDC subjective score, age, and body mass index (BMI)). Histological cartilage tissue score correlated with patients’ IKDC and C2C and CPII biomarkers. CPII correlated also with histological bone tissue score. The percentage of CD146 positive cells in cartilage and CD34 positive cells in bone highly correlated with the patient’s age and BMI, respectively. The percentage of TRAP in bone was directly correlated with both IKDC and age. Multivariate statistical analysis evidenced that only four parameters significantly predicted IKDC. In conclusion, a complete picture of OCD knee characteristics, defined by local and systemic markers of cartilage and bone remodeling, together with the patients’ characteristics, might help to better understand the healing potential of each patient and to target and improve current OCD treatments.
An Inguinal Perivascular Epithelioid Cell Tumor Metastatic to the Orbit
Authors: Tynski Zofia , Chiang Way , Barrett Albert
Published: May 2018

Malignant PEComas are rare mesenchymal neoplasms. These tumors harbor distinct myomelanocytic phenotype. The PEComa family of tumors includes lymphangioleiomyomatosis, angiomyolipoma, clear cell sugar tumor of the lung, and myomelanocytic tumor of the falciparum ligament/ligamentum teres. PEComas have no known normal cell counterpart. Majority of PEComas are benign and occur predominantly in the middle-age women. These tumors are commonly encountered in the uterus. Herein, we report a 20-year-old woman with a left inguinal mass metastatic to orbit, brain, lumbar spine, and skin at presentation. To our knowledge, this is the first case of metastatic PEComa to the orbit. This is the third case of primary PEComa of the inguinal area.
The Role of Combination Maintenance with Pemetrexed and Bevacizumab for Advanced Stage Nonsquamous Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Shan Feiyu , Zhang Bo , Sun Leitao , Xie Lufan , Shen Minhe , Ruan Shanming
Published: May 2018

Purpose. To evaluate the effect of combination maintenance therapy of pemetrexed plus bevacizumab for patients with advanced non-small cell lung cancer. Methods. We identified relevant studies by electronic search (Embase, PubMed, Cochrane, and Web of Science from 1 January 1960 to 29 October 2016) and manual search. The primary outcome of interest was progression-free survival (PFS) and secondary end point included overall survival (OS) and toxicities. The data was pooled for quantitative analysis and the final effect size was reported as hazard ratio (HR) for survival outcomes and relative risk (RR) for safety outcomes, both with a random-effects model. Results. Three randomized controlled trials enrolling 1302 patients with advanced non-small cell lung cancer were included in this meta-analysis. An evident PFS improvement (HR = 0.73, 95% CI = 0.63–0.83, P < 0.01) was observed in patients with pemetrexed and bevacizumab combination maintenance therapy compared with single-agent maintenance therapy, yet it did not subsequently lead to a significant improvement in OS (HR = 0.97, 95% CI = 0.84–1.10, P = 0.66). Our analysis also showed statistically increased risks for provoking grade 3-4 adverse events in patients managed using pemetrexed plus bevacizumab combination (RR = 1.59, 95% CI = 1.07–2.36, P = 0.022). Conclusions. Pemetrexed plus bevacizumab combination maintenance therapy leads to significant improvement in PFS but not in OS for patients with advanced non-small cell lung cancer, which also increases the risks of grade 3-4 adverse events. Yet, in view of the limitation of existing studies and this meta-analysis, current evidence is not adequate to support routine use of pemetrexed-bevacizumab maintenance.
A Strategy for Automatic Performance Tuning of Stencil Computations on GPUs
Authors: Garvey Joseph D. , Abdelrahman Tarek S.
Published: May 2018

We propose and evaluate a novel strategy for tuning the performance of a class of stencil computations on Graphics Processing Units. The strategy uses a machine learning model to predict the optimal way to load data from memory followed by a heuristic that divides other optimizations into groups and exhaustively explores one group at a time. We use a set of 104 synthetic OpenCL stencil benchmarks that are representative of many real stencil computations. We first demonstrate the need for auto-tuning by showing that the optimization space is sufficiently complex that simple approaches to determining a high-performing configuration fail. We then demonstrate the effectiveness of our approach on NVIDIA and AMD GPUs. Relative to a random sampling of the space, we find configurations that are 12%/32% faster on the NVIDIA/AMD platform in 71% and 4% less time, respectively. Relative to an expert search, we achieve 5% and 9% better performance on the two platforms in 89% and 76% less time. We also evaluate our strategy for different stencil computational intensities, varying array sizes and shapes, and in combination with expert search.
Conformable Fractional Integrals Versions of Hermite-Hadamard Inequalities and Their Generalizations
Authors: Adil Khan Muhammad , Chu Yu-Ming , Kashuri Artion , Liko Rozana , Ali Gohar
Published: May 2018

We prove new Hermite-Hadamard inequalities for conformable fractional integrals by using convex function, s-convex, and coordinate convex functions. We prove new Montgomery identity and by using this identity we obtain generalized Hermite-Hadamard type inequalities.
Transient Analysis of a Functionally Graded Ceramic/Metal Layer considering Lord-Shulman Theory
Authors: Nikolarakis Antonios M. , Theotokoglou Efstathios E.
Published: May 2018

The transient displacement, temperature, and stress fields in a functionally graded ceramic/metal layer under uniform thermal shock conditions at the upper surface are numerically studied based on the Lord-Shulman model, employing a direct finite element method. The Newmark method is employed for the time integration of the problem. A Matlab finite element code is developed for the numerical analysis of the one-dimensional problem under consideration. The Voigt model (rule of mixture) is used for the estimation of the effective properties inside the functionally graded layer and the variation of the volume fraction of the materials follows the sigmoid function in terms of the introduced parameter p. Furthermore, a parametric study with respect to the parameter p follows, where three different combinations of ceramic/metal materials are considered. It is concluded that the value p=1, which corresponds to a linear variation of the properties, minimizes the maximum (tensile) stress applied at the middle of the functionally graded layer.
Infants Are More Likely Than Older Children to Have Surgery for Cervical Infections
Authors: Harounian Jonathan A. , Azab Andrew R. , Roberts Christopher A. , Carr Michele M.
Published: May 2018

Objectives. To identify differences in cervical infection management in infants versus older children. Methods. Charts of patients 0–18 years, diagnosed with a cervical infection at our institution between 2004 and 2015, were included. Age, gender, presenting symptoms, comorbidities, CT scan findings and management including admission, procedures, antibiotics, cultures, length of stay, readmission rates, and complications were included. Results. 239 patients were included: mean age was 4.6 years, with 55.6% boys and 44.4% girls. Mean length of stay was 3.2 days, with no significant difference between age categories. 12.55% were readmitted within 30 days with no significant difference when stratified for age (p = 0.268). The most common presenting symptoms were fever (74.3%), swelling (71.4%), and neck pain (48.2%). Infants had fewer symptoms documented than older children. 51% has lateral neck infections, and these were more common in younger children (p < 0.001). The most common antibiotic used was amoxicillin-clavulanic acid in 53.96% of inpatients and 48.05% of outpatients. Infants were most likely to have MRSA isolates (29.2% versus 11.7% of older children, p = 0.011). 70.0% went to the operating room for incision and drainage procedures. Younger children were more likely to undergo surgery, with an odds ratio of 2.38 for children under 1 year. (p = 0.029). 90.9% of infants underwent surgery with radiolucencies of at least 1 cm diameter in contrast to 50% of children over 8 years old. Conclusions. This study emphasizes the importance of considering early operative treatment of cervical abscesses in infants despite fewer symptoms and smaller radiolucencies on CT.
Hei-Gu-Teng Zhuifenghuoluo Granule Modulates IL-12 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis
Authors: Zheng Kang , Chen Zexu , Sun Wen , Liu Bin , Fan Danping , Guo Qingqing , Luo Hui , Shen Jiawen , Li Li , He Xiaojuan , Kou Shuang , Li Xiaoya , Pang Guoming , Zhao Hongchuan , Lu Cheng
Published: May 2018

Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) likeTripterygium wilfordiiHook. F. orSinomenium acutum(Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which containsPeriploca forrestii Schltr.,Sinomenium acutum(Thunb.) Rehd et Wils., andLysimachia paridiformisFranch.var.stenophyllaFranch.was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis within vivoandin vitroexperiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice modelin vivoand U937 cell modelin vitro.The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger.In vivoexperiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway.In vitroexperiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.
A Service‐Based Method for Multiple Sensor Streams Aggregation in Fog Computing
Authors: Zhang Zhongmei , Liu Chen , Zhang Shouli , Li Xiaohong , Han Yanbo
Published: May 2018

A surge in sensor data volume has exposed the shortcomings of cloud computing, particularly the limitation of network transmission capability and centralized computing resources. The dynamic intervention among sensor streams also brings challenges for IoT applications to derive meaningful information from multiple sensor streams. To handle these issues, this paper proposes a service‐based method with fog computing paradigm based on our previous service abstraction, which can capture meaningful events from multiple sensor streams. In our service abstraction, we utilize correlation analysis method to capture events as variations of correlation among sensor streams. Facing inconsistent frequency and shift of correlation, we propose a Dynamic Time Warping‐ (DTW‐) based algorithm to obtain sensor streams’ lag‐correlation. For adaptively aggregating related events from different services, we also propose an event routing algorithm to assist the composition of cascaded events through service collaboration. This paper reports the tryout use of our method in Chinese power grid for detecting abnormal situations of power quality. Through a series of experiments based on real sensor data in power grid, we verified that our method can reduce the network transmission and computing resource with high accuracy.
Lactobacillus plantarum with Functional Properties: An Approach to Increase Safety and Shelf-Life of Fermented Foods
Authors: Behera Sudhanshu S. , Ray Ramesh C. , Zdolec Nevijo
Published: May 2018

Lactobacillus plantarum (widespread member of the genus Lactobacillus) is one of the most studied species extensively used in food industry as probiotic microorganism and/or microbial starter. The exploitation of Lb. plantarum strains with their long history in food fermentation forms an emerging field and design of added-value foods. Lb. plantarum strains were also used to produce new functional (traditional/novel) foods and beverages with improved nutritional and technological features. Lb. plantarum strains were identified from many traditional foods and characterized for their systematics and molecular taxonomy, enzyme systems (α-amylase, esterase, lipase, α-glucosidase, β-glucosidase, enolase, phosphoketolase, lactase dehydrogenase, etc.), and bioactive compounds (bacteriocin, dipeptides, and other preservative compounds). This review emphasizes that the Lb. plantarum strains with their probiotic properties can have great effects against harmful microflora (foodborne pathogens) to increase safety and shelf-life of fermented foods.
Diagnostic Benefit of Simultaneous Capsule Endoscopy Using Two Different Systems
Authors: Kim Seung Han , Choi Hyuk Soon , Chun Hoon Jai , Kim Eun Sun , Keum Bora , Seo Yeon Seok , Jeen Yoon Tae , Lee Hong Sik , Um Soon Ho , Kim Chang Duck
Published: May 2018

Background/Aims. Capsule endoscopy (CE) is a noninvasive test for diagnosing small bowel disorders. However, several studies reported that the CE-based visualization is suboptimal. This study, the first to use two CEs simultaneously, aimed at evaluating the diagnostic ability of dual CE. Methods. Dual CE procedures were prospectively conducted. All patients completed bowel cleansing 2 hours before examination. Subsequently, they simultaneously swallowed two capsules: MiroCam (IntroMedic, Seoul, Korea) and PillCam SB3 (Medtronic, Minneapolis, USA). We assessed the completeness and feasibility of small bowel examination and the detection rate of duodenal papilla and diagnostic yield. Results. Twenty consecutive patients who underwent complete small bowel examination with dual CE were enrolled in the study. The mean time of small bowel passage was 245 ± 99 min. Dual CE examination increased the duodenal papilla detection rate to up to 75% (versus PillCam SB3 alone (P=0.031) and MiroCam alone (P=0.063)) and overall diagnostic yield to up to 70% (P=0.063) in comparison to single CE. Adverse events or electrical interference during data transmission between the two capsule endoscopes were not detected. Conclusions. In this study, we found that dual CE enhances diagnostic accuracy and could increase the diagnostic power of existing CE systems using simply applicable methods. This trial is registered with KCT0002541.
Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma
Authors: Olmez Inan , Zhang Ying , Manigat Laryssa , Benamar Mouadh , Brenneman Breanna , Nakano Ichiro , Godlewski Jakub , Bronisz Agnieszka , Lee Jeongwu , Abbas Tarek , Abounader Roger , Purow Benjamin
Published: May 2018

Glioblastoma (GBM) is the most common primary brain malignancy and carries an extremely poor prognosis. Recent molecular studies revealed the CDK4/6-Rb-E2F axis and receptor tyrosine kinase (RTK) signaling to be deregulated in most GBM, creating an opportunity to develop more effective therapies by targeting both pathways. Using a phospho-RTK protein array, we found that both c-Met and TrkA-B pathways were significantly activated upon CDK4/6 inhibition in GBM cells. We therefore investigated the efficacy of combined CDK4/6 and c-Met/TrkA-B inhibition against GBM. We show that both c-Met and TrkA-B pathways transactivate each other, and targeting both pathways simultaneously results in more efficient pathway suppression. Mechanistically, inhibition of CDK4/6 drove NF-κB–mediated upregulation of hepatocyte growth factor, brain-derived neurotrophic factor, and nerve growth factor that in turn activated both c-Met and TrkA-B pathways. Combining the CDK4/6 inhibitor abemaciclib with the c-Met/Trk inhibitor altiratinib or the corresponding siRNAs induced apoptosis, leading to significant synergy against GBM. Collectively, these findings demonstrate that the activation of c-Met/TrkA-B pathways is a novel mechanism involved in therapeutic resistance of GBM to CDK4/6 inhibition and that dual inhibition of c-Met/Trk with CDK4/6 should be considered in future clinical trials.

Significance: CDK4/6 inhibition in glioblastoma activates the c-Met and TrkA-B pathways mediated by NF-κB and can be reversed by a dual c-Met/Trk inhibitor. Cancer Res; 78(15); 4360–9. ©2018 AACR.
FGFR1-Activated Translation of WNT Pathway Components with Structured 5′ UTRs Is Vulnerable to Inhibition of EIF4A-Dependent Translation Initiation
Authors: Nguyen Tuan M. , Kabotyanski Elena B. , Dou Yongchao , Reineke Lucas C. , Zhang Peng , Zhang Xiang H.-F. , Malovannaya Anna , Jung Sung Yun , Mo Qianxing , Roarty Kevin P. , Chen Yiwen , Zhang Bing , Neilson Joel R. , Lloyd Richard E. , Perou Charles M. , Ellis Matthew J. , Rosen Jeffrey M.
Published: May 2018

Cooperativity between WNT and FGF signaling is well documented in embryonic development and cancer progression, but the molecular mechanisms underlying this cross-talk remain elusive. In this study, we interrogated the dynamics of RNA levels, ribosome occupancy, and protein expression as a function of inducible FGF signaling in mouse mammary glands with constitutive WNT hyperactivation. Multiomics correlation analysis revealed a substantial discrepancy between RNA and ribosome occupancy levels versus protein levels. However, this discrepancy decreased as cells became premalignant and dynamically responded to FGF signaling, implicating the importance of stringent gene regulation in nontransformed cells. Analysis of individual genes demonstrated that acute FGF hyperactivation increased translation of many stem cell self-renewal regulators, including WNT signaling components, and decreased translation of genes regulating cellular senescence. WNT pathway components translationally upregulated by FGF signaling had long and structured 5′ UTRs with a high frequency of polypurine sequences, several of which harbored (CGG)4 motifs that can fold into either stable G-quadruplexes or other stable secondary structures. The FGF-mediated increase in translation of WNT pathway components was compromised by silvestrol, an inhibitor of EIF4A that clamps EIF4A to polypurine sequences to block 43S scanning and inhibits its RNA-unwinding activity important for translation initiation. Moreover, silvestrol treatment significantly delayed FGF-WNT–driven tumorigenesis. Taken together, these results suggest that FGF signaling selectively enhances translation of structured mRNAs, particularly WNT signaling components, and highlight their vulnerability to inhibitors that target the RNA helicase EIF4A.

Significance: The RNA helicase EIF4A may serve as a therapeutic target for breast cancers that require FGF and WNT signaling. Cancer Res; 78(15); 4229–40. ©2018 AACR.
The Role of Salvage High-Dose Chemotherapy in Relapsed Male Germ Cell Tumors
Authors: Oing Christoph , Lorch Anja
Published: May 2018

Germ cell tumors (GCT) are a unique tumor entity with excellent cure rates if guideline-endorsed treatment is thoroughly applied. Even patients with widespread metastatic disease can often be cured with cisplatin-based combination chemotherapy as part of a multimodal treatment approach. However, about 30% of patients with metastatic disease at initial presentation, corresponding to about 5-10% of all GCT patients, relapse or progress despite first-line treatment and therefore require salvage chemotherapy. Salvage systemic treatment either consists of conventional-dose cisplatin-based combination chemotherapy or sequential high-dose treatment with carboplatin and etoposide plus subsequent autologous stem cell support. This review is based on a comprehensive literature search of MEDLINE and conference proceedings of ESMO, ASCO, and EAU meetings until 2018 and provides an overview of current treatment options for germ cell cancer patients relapsing after or progressing during first-line cisplatin-based combination chemotherapy.
Crosstalk of NF-κB/P65 and LncRNA HOTAIR-Mediated Repression of MUC1 Expression Contribute to Synergistic Inhibition of Castration-Resistant Prostate Cancer by Polyphyllin 1–Enzalutamide Combination Treatment
Authors: Xiang SongTao , Zou PeiLiang , Wu JingJing , Zheng Fang , Tang Qing , Zhou Jianfu , Hann Swei Sunny
Published: May 2018

Background/Aims: Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, reportedly exhibits antitumor effects. However, the detailed mechanism underlying PPI, particularly in enhancing the effect of the androgen receptor inhibitor enzalutamide in controlling castration-resistant prostate cancer (CRPC) has not been explored. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) expression was measured by quantitative real time-PCR (qRT-PCR). Western blot analysis was performed to determine the protein expression levels of MUC1, p65, and p50. Silencing of HOTAIR was evaluated using the siRNA procedure. The promoter activity of the MUC1 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expression of HOTAIR, p65, and MUC1 was conducted by transient transfection assay. A xenograft tumor model in nude mice was used to further evaluate the effect of the combination of PPI and enzalutamide in vivo. Results: We showed that PPI significantly inhibited growth and induced cell cycle arrest in CRPC cells. PPI also decreased p65 and MUC1 protein expression and reduced HOTAIR expression. Exogenously expressed p65 resisted the PPI-inhibited expression of HOTAIR, whereas silenced HOTAIR reduced MUC1 protein but exerted no effect on the expression of p65 and p50 proteins. Conversely, exogenously expressed HOTAIR resisted the PPI-inhibited MUC1 protein expression, and excessive expression of MUC1 antagonized the PPI-inhibited cell growth. Notably, PPI combined with enzalutamide exerted a synergistic effect. Consistent with this finding, PPI inhibited tumor growth, HOTAIR expression, as well as p65 and MUC1 protein expressions in vivo. Conclusions: Our results indicate that PPI inhibits the growth of CRPC cells by inhibiting p65 protein and concomitantly reducing HOTAIR expression, thereby suppressing MUC1 gene expression. The novel regulatory interaction of p65 and HOTAIR converge in the inhibition of MUC1 expression and overall PPI response. The combination of PPI and enzalutamide exhibits synergy. This study reveals a novel mechanism underlying the synergistic inhibitory effect of PPI and enzalutamide on the growth of CRPC cells.
Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability
Authors: Peng Jun , Yu Jingwei , Xu Hu , Kang Chen , Shaul Philip W. , Guan Youfei , Zhang Xiaoyan , Su Wen
Published: May 2018

Background/Aims: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration. Methods: 2/3 partial hepatectomy (PH) was performed in wild type C57BL/6J (WT) and Srebp-1c-/- mice. The lipid contents in serum and liver were measured by enzymatic colorimetric methods. Hepatic lipid droplets were detected by Oil Red O staining and immunohistological staining. Hepatic expression of genes involved in lipid metabolism and cellular proliferation was determined by real-time PCR and/or immunoblot. Hepatocyte proliferation and liver regeneration were assessed by BrdU staining and the weight of remanent liver lobes in Srebp-1c-/- mice, respectively. Results: Srebp-1c-/- mice displayed reduced triglyceride and fatty acids but increased cholesterol in the liver before PH. In response to PH, hepatocellular DNA synthesis was elevated and cell cycle progression was prolonged in Srebp-1c-/- mice, which was associated with enhanced liver regeneration. However, Srebp-1c-/- mice had comparable triglyceride and fatty acid contents and expressions of related genes compared with WT mice during the liver regeneration. In contrast, SREBP-1c-deficiency-induced alteration of cholesterol metabolism was retained during the liver regeneration after PH. Srebp-1c-/- mice exhibited higher cholesterol contents and enhanced expression of SREBP-2 and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in the liver than WT mice after PH. Moreover, downregulation of genes involved in cholesterol elimination was observed after PH in Srebp-1c-/- mice. Conclusion: SREBP-1c deficiency in mice did not interfere with triglyceride and fatty acid metabolism but was associated with significant changes in cholesterol profiles during liver regeneration after PH. These results suggest that increased hepatocellular cholesterol storage and cholesterol availability with the enhanced liver regeneration are identified in Srebp-1c-/- mice. This study also shows that providing requisite cholesterol levels to proliferating hepatocytes and keeping appropriate cholesterol metabolism are required for normal liver regeneration.
Trefoil Factor 3 Deficiency Affects Liver Lipid Metabolism
Authors: Bujak Maro , Bujak Ivana Tartaro , Sobočanec Sandra , Mihalj Martina , Novak Sanja , Ćosić Anita , Levak Maja Tolušić , Kopačin Vjekoslav , Mihaljević Branka , Balog Tihomir , Drenjančević Ines , Loncar Mirela Baus
Published: May 2018

Background/Aims: Tff3 protein plays a well recognized role in the protection of gastrointestinal mucosa. The role of Tff3 in the metabolism is a new aspect of its function. Tff3 is one of the most affected liver genes in early diabetes and fatty liver rodent models. The aim of this study was to investigate the effect of Tff3 deficiency on lipid and carbohydrate metabolism and on markers of oxidative stress that accompanies metabolic deregulation. Methods: Specific markers of health status were determined in sera of Tff3 deficient mice, including glucose level, functional glucose and insulin tolerance. Composition of fatty acids (FAs) was determined in liver and blood serum by using gas chromatography. Oxidative stress parameters were determined: lipid peroxidation level via determination of lipid hydroperoxide and thiobarbituric acid reactive substances (TBARS), antioxidative capacity (FRAP) and specific antioxidative enzyme activity. The expression of several genes and proteins related to the metabolism of lipids, carbohydrates and oxidative stress (CAT, GPx1, SOD2, PPARα, PPARγ, PPARδ, HNF4α and SIRT1) was determined. Results: Tff3 deficient mice showed better glucose utilization in the glucose and insulin test. Liver lipid metabolism is affected and increased formation of small lipid vesicles is noticed. Formation of lipid droplets is not accompanied by increased liver oxidative stress, although expression/activity of monitored enzymes is deregulated when compared with wild type mice. Tff3 deficient mice exhibit reduced expression of metabolism relevant SIRT1 and PPARγ genes. Conclusion: Tff3 deficiency affects the profile and accumulation of FAs in the liver, with no obvious oxidative stress increase, although expression/activity of monitored enzymes is changed as well as the level of SIRT1 and PPARγ protein. Considering the strong downregulation of liver Tff3 in diabetic/obese mice, presence in circulation and regulation by food/insulin, Tff3 is an interesting novel candidate in metabolism relevant conditions.
Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization
Authors: Jiang Mei , Wang Hairong , Jin Mingming , Yang Xuelian , Ji Haifeng , Jiang Yufeng , Zhang Hanwen , Wu Feifei , Wu Guolu , Lai Xiaoyin , Cai Liying , Hu Rongguo , Xu Limin , Li Longxuan
Published: May 2018

Background/Aims: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). Methods: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. Results: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. Conclusions: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.
A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer
Authors: Wang Pengcheng , Li Jing , Zhao Wei , Shang Chunyang , Jiang Xian , Wang Yuli , Zhou Baoguo , Bao Fusheng , Qiao Haiquan
Published: May 2018

Background/Aims: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. Methods: We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. Results: We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. Conclusions: This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.
Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner
Authors: Gu Chen Juan , Yi Hua Hua , Feng Jing , Zhang Zhi Guo , Zhou Jun , Zhou Li Na , Zhou Jian Ping , Li Min , Li Qing Yun 
Published: May 2018

Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. Methods: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.
Iluminação artificial aplicada à arquitetura: processo de projeto
Authors: Bandeira Fernanda Brito , Scarazzato Paulo Sergio
Published: May 2018

O processo de projeto, com todos os elementos que o caracterizam, é responsável pela qualidade do projeto como um todo. No Brasil, no caso de projetos de iluminação para edificações, pouco se discute sobre o seu processo de projeto, apesar do aumento de cursos de pós-graduação nesta subárea da arquitetura na última década. Este artigo apresenta alguns aspectos que, atualmente, são considerados no processo de projeto de iluminação artificial aplicado à arquitetura, segundo o entendimento de projetistas especialistas que dedicam sua atuação profissional majoritariamente a projetos de iluminação. Os especialistas foram consultados por meio de questionário eletrônico, e as questões foram desenvolvidas a partir de revisão bibliográfica temática. Os elementos consultados foram as fases de projeto, ferramentas de apoio, conceitos de qualidade de iluminação e problemas enfrentados na rotina projetual. Na sequência, a fim de delinear o processo de projeto, os resultados foram analisados com base na compilação das respostas que indicaram as atividades profissionais. Além de identificar como se dá o processo de projeto dos participantes, as respostas dos questionários indicaram que algumas fases de projeto e variáveis de projeto preconizadas na literatura não são aplicadas na sua totalidade por todos os profissionais. Também foi identificada alta incidência de alguns problemas na rotina projetual.
Design, tecnologia e patrimônio: digitalização tridimensional como ferramenta de preservação de elementos de prédios históricos
Authors: Muniz Guilherme Resende , Silva Fabio Pinto da , Kindlein Júnior Wilson
Published: May 2018

O design voltado para o patrimônio, atuando em conjunto com a digitalização tridimensional, abre um novo campo para a preservação de bens culturais. Nesse contexto, elaborou-se um projeto com finalidades histórico-pedagógicas para escanear em 3D quatro elementos de fachada de prédios históricos da Universidade Federal do Rio Grande do Sul, utilizando a técnica de luz estruturada. Após uma análise prévia do local dos elementos, realizou-se um breve levantamento histórico sobre cada um. Como resultado, após o tratamento dos dados adquiridos, foi possível comparar os modelos reais com os modelos digitalizados em 3D. Também foram disponibilizados os dados técnicos das digitalizações de cada elemento. Por fim, foi elaborado um fluxograma com as tomadas de decisões realizadas durante o projeto, e os modelos virtuais tiveram seu tamanho reduzido para então serem disponibilizados para visualização on-line.