bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated characterisation of cancer genes identifies key molecular biomarkers in stomach adenocarcinoma
Authors: Wang Haifeng , Shen Liyijing , Li Yaoqing , Lv Jieqing
Published: February 2020

Aims

Gastric cancer is one of the leading causes for cancer mortality. Recent studies have defined the landscape of genomic alterations of gastric cancer and their association with clinical outcomes. However, the pathogenesis of gastric cancer has not been completely characterised.

Methods

Driver genes were detected by five computational tools, MutSigCV, OncodriveCLUST, OncodriveFM, dendrix and edriver, using mutation data of stomach adenocarcinoma (STAD) from the cancer genome altas database, followed by an integrative investigation.

Results

TTN, TP53, LRP1B, CSMD3, OBSCN, ARID1A, FAT4, FLG, PCLOandCSMD1were the 10 most frequently mutated genes.PIK3CD, NLRC3, FMNL1, TRAF3IP3andCR1were the top five hub genes of the blue coexpression module positively correlated with pathological tumour stage and lymph node stage (p values <0.05 for all cases). Hierarchical clustering analysis of copy number variations of driver genes revealed three subgroups of STAD patients, and cluster 2 tumours were significantly associated with lower lymph node stage, less number of positive lymph nodes and higher microsatellite instability and better overall survival than cluster 1 and cluster 3 tumours (p values <0.05 for all cases, Wilcoxon rank-sum test or log rank test). High expression in one or more ofDNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29andZNF568genes was associated with increased mortality (p values <0.05 for all cases, log rank test).

Conclusions

The driver genes shed insights into the tumourigenesis of gastric cancer and the genesDNER, LHCGR, NLRP14, OR4N2, PSG6, TTC29andZNF568pave the way for developing prognostic biomarkers for the disease.
Distinct influence of different vascular risk factors on white matter brain lesions in multiple sclerosis
Authors: Geraldes Ruth , Juryńczyk Maciej , dos Passos Giordani , Prichler Alexander , Chung Karen , Hagens Marloes , Ruggieri Serena , Huerga Elena , Sastre-Garriga Jaume , Enzinger Christian , Chard Declan T , Barkhof Frederik , Gasperini Claudio , Rovira Alex , DeLuca Gabriele C , Palace Jacqueline
Published: February 2020

Objective

To determine if vascular risk factor (VRF), that is, smoking, arterial hypertension (HT), dyslipidaemia and diabetes, have an effect on multiple sclerosis (MS) pathology as measured by MS typical brain lesions, we have compared brain MRIs from patients with MS with and without VRF age-matched and sex-matched.

Methods

Brain MRIs from five centres were scored for the presence of Dawson’s fingers (DF) and juxtacortical lesions (JCL). A regression model was built to predict the effect of each individual VRF on DF and JCL, considering age and disease duration.

Results

92 MS cases without VRF and 106 MS with one or more VRF (80 ever-smokers, 43 hypertensives, 25 dyslipidaemics and 10 diabetics) were included. Ever-smoking associated with a higher burden of DF (Exp(B)=1.29, 95% CI 1.10 to 1.51, p<0.01) and JCL (Exp(B)=1.38, 95% CI 1.21 to 1.57, p<0.01). No other VRF had an impact on DF. Dyslipidaemia associated with increased JCL (Exp(B)=1.30, 95% CI 1.10 to 1.56, p<0.01) but HT did not associate with any of the outcomes.

Conclusions

Individual VRF appear to affect MS-specific lesions differently. An increase in MS lesions was mainly seen in smokers; however, this VRF is most likely to be present from onset of MS, and other VRF effects may be partly mitigated by treatment. Our findings support that treating VRF and cessation of smoking may be important in the management of MS.
Screening of lupine germplasm for resistance againstPhytophthora sojae
Authors: Beligala Gayathri U. , Michaels Helen J. , Phuntumart Vipaporn
Published: February 2020

Phytophthora sojae is a major pathogen in cultivated soybeans world-wide. Although incorporating resistance genes has been an effective management tool for soybean breeders, surveys of soybean fields in the Midwest US indicate that some P. sojae strains are capable of overcoming all known resistance genes. While P. sojae is known to have a very narrow host range, it can also infect Lupinus (lupine), varieties of which may provide potential sources for novel resistance genes that can be genetically engineered into soybean. The chemotactic behavior of zoospores and pathogenicity of P. sojae strain P6497 towards 17 lupine lines were explored. The two soybean varieties Williams and Williams 82 that are susceptible and resistant against P. sojae P6497, respectively, were used as controls. Chemotaxis assays showed that there was no coherent pattern between the number of zoospores colonizing the root surface and plant tolerance or resistance to phytophthora root rot. Pathogenicity tests identified that two of the 17 lupine lines tested (LAB 18 and LL 35) were resistant to P. sojae infection. Phylogenetic analysis of these two resistant lupine lines with Old World lupines of the Mediterranean and North African regions, and New World lupines of America, indicated that they originated from the Old World.
Calculated fission-fragment mass yields and average total kinetic energies of heavy and superheavy nuclei
Authors: Albertsson Martin , Carlsson B. Gillis , Døssing Thomas , Möller Peter , Randrup Jørgen , Åberg Sven
Published: February 2020

Fission-fragment mass and total-kinetic-energy (TKE) distributions following fission of even-even nuclides in the region $$74 \le Z \le 126$$74≤Z≤126 and $$92 \le N \le 230$$92≤N≤230, comprising 896 nuclides have been calculated using the Brownian shape-motion method. The emphasis is the region of superheavy nuclei. To show compatibility with earlier results the calculations are extended to include earlier studied regions. An island of asymmetric fission is obtained in the superheavy region, $$106\le Z\le 114$$106≤Z≤114 and $$162\le N\le 176$$162≤N≤176, where the heavy fragment is found to be close to $$^{208}$$208Pb and the light fragment adjusts accordingly. Most experimentally observed $$\alpha $$α-decay chains of superheavy nuclei with $$Z > 113 $$Z>113 terminate by spontaneous fission in our predicted region of asymmetric fission. In these cases, the pronounced large asymmetry is accompanied by a low TKE value compatible with measurements.
How to extend the chart of nuclides?
Authors: Adamian G. G. , Antonenko N. V. , Diaz-Torres A. , Heinz S.
Published: February 2020

In the past 85 years the number of known nuclides increased by more than a factor of ten, resulting in 4000 presently known isotopes of 118 elements. This considerable progress we owe to the discovery of new reaction types along with the development of powerful accelerators and experimental techniques for separation and identification of reaction products. Model predictions indicate that still about 4000 further nuclides are waiting for their discovery. The vastest unexplored territory is located on the neutron-rich side in the upper half of the chart of nuclides and hides the answers to some of the most fundamental questions of nuclear physics like the limits of nuclear stability, element synthesis in the universe or stellar evolution. The access to these nuclei is presently limited by available beam intensities and/or the lack of appropriate methods for their production and identification. The latter concerns particularly new neutron-rich isotopes of transuranium and superheavy elements. To extend this area, the hope is presently based on multinucleon transfer reactions and on the application of fusion reactions with radioactive ion beams. But how promising are these approaches? Based on a survey of present-day knowledge, we will treat the questions where we currently are on our journey towards new territory on the chart of nuclides, how the chances are to gain new territory in the future and which challenges we will have to face.
Interplay between Constraints and Rewards in Innovation Tournaments: Implications for Participation
Authors: Deodhar Swanand J.
Published: February 2020

In this study, we examine how the monetary rewards and competitive constraints that organizers of innovation tournaments incorporate are associated with participation. These two aspects of innovation tournaments are crucial because they represent critical design decisions that the organizers must make beforehand. We show that the reward amount is negatively associated with participation, while the presence of competitive constraints, which “make the competitive landscape less asymmetric”, is positively associated with participation. Furthermore, the study shows that competitive constraints moderate the negative association between reward amount and participation. These findings provide insights into contestant motivation as well as the interdependencies between tournament design choices.
Detection of Suture Needle Using Deep Learning
Authors: Mei Qipei , Chainey Jonathan , Asgar-Deen David , Aalto Daniel
Published: February 2020

The importance of surgical simulation has increased over the last decade and the majority of medical schools have incorporated simulation into their curriculum. An essential aspect of surgical education is to evaluate how the student performs when compared to an expert surgeon. Another way to evaluate the skill of the student would be by tracking the position of the needle during the procedure, a factor correlating to surgical skill. In this study, we developed deep learning algorithms for needle detection during a video of a surgical procedure. 78 videos of a person doing a running suture on synthetic skin were captured using an HD camera. A total of 3368 images were manually annotated with a VGG annotator tool. Two deep learning algorithms (YOLOv3 and Faster R-CNN) were pretrained on 2219 images extracted from the JIGSAWS dataset, then trained on the 804 images from the training set and finally applied to the 345 images from the evaluation set. The performance of the algorithm was evaluated using the intersection over union (IoU) method as well as by measuring the Euclidean distance between bounding box centroids. These values were compared against the inter-observer reliability among three authors. The best IoU value by deep learning algorithms compared against the ground truth was found to be 0.601 for Faster R-CNN while the average inter-observer value was 0.663. The average Euclidean distances between bounding box centroids for authors and for the Faster R-CNN algorithm were 21.9 pixels and 36.8 pixels, respectively. Through qualitative and quantitative assessment of the algorithm (visually observing the algorithm’s needle annotations), deep learning shows promise for automatically tracking the position of the needle during a suturing operation.
Optimizing Deep Learning Inference on Embedded Systems Through Adaptive Model Selection
Authors: Marco Vicent Sanz , Taylor Ben , Wang Zheng , Elkhatib Yehia
Published: February 2020

Deep neural networks (DNNs) are becoming a key enabling technique for many application domains. However, on-device inference on battery-powered, resource-constrained embedding systems is often infeasible due to prohibitively long inferencing time and resource requirements of many DNNs. Offloading computation into the cloud is often unacceptable due to privacy concerns, high latency, or the lack of connectivity. Although compression algorithms often succeed in reducing inferencing times, they come at the cost of reduced accuracy.

This article presents a new, alternative approach to enable efficient execution of DNNs on embedded devices. Our approach dynamically determines which DNN to use for a given input by considering the desired accuracy and inference time. It employs machine learning to develop a low-cost predictive model to quickly select a pre-trained DNN to use for a given input and the optimization constraint. We achieve this first by offline training a predictive model and then using the learned model to select a DNN model to use for new, unseen inputs. We apply our approach to two representative DNN domains: image classification and machine translation. We evaluate our approach on a Jetson TX2 embedded deep learning platform and consider a range of influential DNN models including convolutional and recurrent neural networks. For image classification, we achieve a 1.8x reduction in inference time with a 7.52% improvement in accuracy over the most capable single DNN model. For machine translation, we achieve a 1.34x reduction in inference time over the most capable single model with little impact on the quality of translation.
Improving Implicit Recommender Systems with Auxiliary Data
Authors: Ding Jingtao , Yu Guanghui , Li Yong , He Xiangnan , Jin Depeng
Published: February 2020

Most existing recommender systems leverage the primary feedback only, despite the fact that users also generate a large amount of auxiliary feedback. These feedback usually indicate different user preferences when comparing to the primary feedback directly used to optimize the system performance. For example, in E-commerce sites, view data is easily accessible, which provides a valuable yet weaker signal than the primary feedback of purchase. In this work, we improve implicit feedback-based recommender systems (dubbed
Implicit Recommender Systems
) by integrating auxiliary view data into matrix factorization (MF). To exploit different preference levels, we propose both pointwise and pairwise models in terms of how to leverage users’ viewing behaviors. The latter model learns the pairwise ranking relations among purchased, viewed, and non-viewed interactions, being more effective and flexible than the former pointwise MF method. However, such a pairwise formulation poses a computational efficiency problem in learning the model. To address this problem, we design a new learning algorithm based on the
element-wise Alternating Least Squares
 (eALS) learner. Notably, our designed algorithm can efficiently learn model parameters from the whole user-item matrix (including all missing data), with a rather low time complexity that is dependent on the observed data only. Extensive experiments on two real-world datasets demonstrate that our method outperforms several state-of-the-art MF methods by 6.43%∼ 6.75%. Our implementation is available at https://github.com/dingjingtao/Auxiliary_enhanced_ALS.
Good Practices for Rechargeable Lithium Metal Batteries
Authors: Wu Bingbin , Yang Yang , Liu Dianying , Niu Chaojiang , Gross Mark , Seymour Lorraine , Lee Hongkyung , Le Phung M. L. , Vo Thanh D. , Deng Zhiqun Daniel , Dufek Eric J. , Whittingham M. Stanley , Liu Jun , Xiao Jie
Published: February 2020

High-energy rechargeable lithium metal batteries have been intensively revisited in recent years. Since more researchers started to use pouch cell as the platform to study the fundamentals at relevant scales, safe testing and handling of lithium metal and high-energy lithium metal batteries have become critical. Cautions and safety procedures are needed when handling cycled pouch cells with pulverized lithium metal particles inside. From cell design, electrode preparation, cell fabrication to testing procedure, this work aims to discuss the possible root causes that may initiate cell internal short circuit and raise safety concerns. Safe transfer, disassembly and disposal of cycled Li metal pouch cells are also discussed. The insights provided in this article are applicable for the research on high-energy lithium-ion batteries as well and may inspire more safety strategies to accelerate research innovation by using large-format batteries as the testing vehicle and conduct the research safely.
From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract
Authors: Le Tortorec Anna , Matusali Giulia , Mahé Dominique , Aubry Florence , Mazaud-Guittot Séverine , Houzet Laurent , Dejucq-Rainsford Nathalie
Published: February 2020

The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.
A Hybrid MCDM Method Using Combination Weight for the Selection of Facility Layout in the Manufacturing System: A Case Study
Authors: Zha Shanshan , Guo Yu , Huang Shaohua , Wang Shengbo
Published: February 2020

Facility layout in the manufacturing system is an elaborate production activity since multiple, uncertain, and conflicting factors would affect facility layout decisions. Selecting the best facility layout among alternatives is considered as a problematic multicriteria decision-making (MCDM) problem. Generally, the facility layout is evaluated by the MCDM method with redundant factors, separate weights, and independent relationships between factors. To overcome this defect, this paper intends to propose a hybrid fuzzy MCDM method with combination weight (CW) based on integration with Delphi, fuzzy ANP, Entropy, and fuzzy PROMETHEE (CW-DFAE-FP) to select the most suitable facility layout alternative in an aircraft assembly workshop. The application results indicate that this method can effectively obtain the most suitable alternative for facility layout selection. Furthermore, the comparative analysis with other MCDM methods verifies the effectiveness of the proposed method and reveals the selection of weight has an impact on final priority ranking. Finally, sensitivity analysis highlights the performance of the proposed method and provides strategic insights to identify the critical criteria for the best alternative in facility layout.
Power Balance Optimization Technology of Microgrid Based on Full-Bridge Converter
Authors: Dai Shuailong , Cao Bin , Liu Rui , Zhu Liyang , Li Mengfan
Published: February 2020

Independent microgrids are widely used in islands and remote townships. However, power imbalance often leads to fluctuations in voltage and frequency, which inhibit the development of AC microgrids. To overcome such problems, this paper proposes an optimized full-bridge converter energy storage structure to realize power balance and optimization of the microgrid. The proposed structure has the characteristics of simple design, easy modularization, and flexible power regulation. First, the working structure and mathematical model are analyzed, and the power model is then established. From the viewpoint of capacitor charging and discharging and inverter, the active and reactive power control technology of the full-bridge structure is analyzed, and a multimode power coordinated control strategy is adopted to adjust and optimize the target power. Finally, the feasibility of the structure and control strategy is verified through a simulation and an experiment. In summary, this study is of great significance to the future promotion and application of AC microgrids.
Assessing the Relationship between the Enhanced Gait Variability Index and Falls in Individuals with Parkinson’s Disease
Authors: Schmitt Abigail C. , Baudendistel Sidney T. , Fallon Michaela S. , Roper Jaimie A. , Hass Chris J.
Published: February 2020

Gait impairment and increased gait variability are common among individuals with Parkinson’s disease (PD) and have been associated with increased risk for falls. The development of composite scores has gained interest to aggregate multiple aspects of gait into a single metric. The Enhanced Gait Variability Index (EGVI) was developed to compare an individual’s gait variability to the amount of variability in a healthy population, yet the EGVI’s individual parts may also provide important information that may be lost in this conversion. We sought to contrast individual gait measures as predictors of fall frequency and the EGVI as a single predictor of fall frequency in individuals with PD. 273 patients (189M, 84F; 68 ± 10 yrs) with idiopathic PD walked over an instrumented walkway and reported fall frequency over three months (never, rarely, monthly, weekly, or daily). The predictive ability of gait velocity, step length, step time, stance time, and single support time and the EGVI was assessed using regression techniques to predict fall frequency. The EGVI explained 15.1% of the variance in fall frequency (p<0.001, r = 0.389). Although the regression using the combined spatiotemporal measures to predict fall frequency was significant (p=0.002, r = 0.264), none of the components reached significance (gait velocity: p=0.640, step length: p=0.900, step time: p=0.525, stance time: p=0.532, single support time: p=0.480). The EGVI is a better predictor of fall frequency in persons with PD than its individual spatiotemporal components. Patients who fall more frequently have more variable gait, based on the interpretation of the EGVI. While the EGVI provides an objective measure of gait variability with some ability to predict fall frequency, full clinical interpretations and applications are currently unknown.
Quantification of Alfacalcidol Tablets Dissolution Content by Chemical Derivatization and LC-MS
Authors: Liu Yang , Chen Xi , Yuan Song , Liu Wanhui , He Lan , Zhang Qingsheng
Published: February 2020

Application of liquid chromatography-mass spectrometry (LC-MS) in analyzing the content of alfacalcidol tablets dissolution faces big challenges due to the low amount of alfacalcidol in each tablet and the low ionization efficacy of the compound with electrospray ionization (ESI) or atmospheric-pressure chemical ionization (APCI). Here, extraction, derivatization, and LC-MS quantitation method have been developed and validated for measuring alfacalcidol tablets dissolution content. After alfacalcidol dissolution solution was extracted with dichloromethane to remove surfactant and inorganic salts, alfacalcidol was then derivatized via a Cookson reagent, 4-phenyl-1, 2, 4-triazoline-3, 5-dione (PTAD), under ambient conditions. Alfacalcidol derivative was successfully analyzed by LC-MS. Limit of detection (LOD) of the derivatized alfacalcidol was improved 100 times (0.01 μg/mL) compared with the nontreated compound (1 μg/mL). The new method was then validated following International Conference on Harmonization (ICH) guidance. The method shows a good linearity with r2 > 0.99. Interday and intraday reproducibility was 3.3% and 7.9%, respectively. This procedure can be used in quantification of alfacalcidol tablets dissolution content and corresponding pharmaceutical quality control.
Determination and Comparative Study of Sugars and Synthetic Colorants in Commercial Branded Fruit Juice Products
Authors: Sewwandi S. D. C. , Arampath P. C. , Silva A. B. G. , Jayatissa R.
Published: February 2020

Fruit juice-based products are potentially high demanded products in Sri Lanka. The research was conducted to estimate the total sugar content in commercially available fruit juice products and to compare the suitability and efficiency of analytical methods: Lane and Eynon titration method and UV-Visible spectrophotometric methods. Further synthetic colorants in the products were identified and compared with the label information. A consumer survey was conducted to elicit information on consumer preference and knowledge on sugar content of the products. Based on the survey, consumers were more concerned about taste (37%), brand name (28%), price (28%), and nutrition value (7%), respectively. Awareness about the Recommended Dietary Allowance (RDA) of sugar, added sugar consumption, and risk of chronic diseases was 49%. Awareness on the color coding system of the products was 68%. The total sugar content of the fruit nectars was determined using both methods. The maximum total sugar level (18.38 g/100 mL) was observed by the titration method, while the maximum total sugar level (18.31 g/100 mL) was measured by the spectrophotometric method in wood apple (Limonia acidissima) nectar in brand No. “1.” The maximum sucrose content (10.57 g/100 mL) was observed in mango (Mangifera indica L.) nectar in the brand No. “1.” Total sugar contents of both tested methods were compared using SAS 9.0 (Randomized Complete Block Design, RCBD). There is no significant difference (P>0.05) between the two testing methods. In conclusion, the Lane and Eynon titration method was identified as the most effective method for analysis of the total sugar in fruit juice-based products. Based on the analysis of thin-layer chromatography (TLC), a majority of fruit nectar samples (57.14%) contained natural colorants, while 42.86% of total samples contained synthetic colorants. Labelling violation was done by the manufacturers, and the consumer awareness was high with the color-coding system. Continuous surveillance is recommended to minimize health risk related to high sugar consumption of the population.
Transient Pressure Analysis for Multifractured Horizontal Well with the Use of Multilinear Flow Model in Shale Gas Reservoir
Authors: Wang Guangdong , Jia Ailin , Wei Yunsheng , Xiao Cong
Published: February 2020

Shale gas reservoirs (SGR) have been a central supply of carbon hydrogen energy consumption and hence widely produced with the assistance of advanced hydraulic fracturing technologies. On the one hand, due to the inherent ultralow permeability and porosity, there is stress sensitivity in the reservoirs generally. On the other hand, hydraulic fractures and the stimulated reservoir volume (SRV) generated by the massive hydraulic fracturing operation have contrast properties with the original reservoirs. These two phenomena pose huge challenges in SGR transient pressure analysis. Limited works have been done to take the stress sensitivity and spatially varying permeability of the SRV zone into consideration simultaneously. This paper first idealizes the SGR to be four linear composite regions. What is more, the SRV zone is further divided into subsections on the basis of nonuniform distribution of proppant within the SRV zone which easily yields spatially varying permeability away from the main hydraulic fracture. By means of perturbation transformation and Laplace transformation, an analytical multilinear flow model (MLFM) is obtained and validated as a comparison with the previous models. The flow regimes are identified, and the sensitivity analysis of critical parameters is conducted to further understand the transient pressure behaviors. The research results provided by this work are of significance for an effective recovery of SGR resources.
Development of High Performance Airfoils for Application in Small Wind Turbine Power Generation
Authors: Osei Emmanuel Yeboah , Opoku Richard , Sunnu Albert K. , Adaramola Muyiwa S.
Published: February 2020

Small wind turbine power generation systems have the potential to meet the electricity demand of the residential sector in developing countries. However, due to their exposure to low Reynolds number (Re) flow conditions and associated problems, specific airfoils are required for the design of their blades. In this research, XFOIL was used to develop and test three high performance airfoils (EYO7-8, EYO8-8, and EYO9-8) for small wind turbine application. The airfoils were subsequently used in conjunction with Blade Element Momentum Theory to develop and test 3-bladed 6 m diameter wind turbine rotors. The aerodynamic performance parameters of the airfoils tested were lift, drag, lift-to-drag ratio, and stall angle. At Re=300,000, EYO7-8, EYO8-8, and EYO9-8 had maximum lift-to-drag ratios of 134, 131, and 127, respectively, and maximum lift coefficients of 1.77, 1.81, and 1.81, respectively. The stall angles were 12° for EYO7-8, 14° for EYO8-8, and 15° for EYO9-8. Together, the new airfoils compared favourably with other existing low Re airfoils and are suitable for the design of small wind turbine blades. Analysis of the results showed that the performance improvement of the EYO-Series airfoils is as a result of the design optimization that employed an optimal thickness-to-camber ratio (t/c) in the range of 0.85–1.50. Preliminary wind turbine rotor analysis also showed that the EYO7-8, EYO8-8, and EYO9-8 rotors had maximum power coefficients of 0.371, 0.366, and 0.358, respectively.
Monitoring of CO2 Absorption Solvent in Natural Gas Process Using Fourier Transform Near-Infrared Spectrometry
Authors: Yusop Nurida Mohd , Norfadilah Dolmat , Siti Aishah Mohd Rozaiddin , Zhe Phak Chan , Saleh Syafiqa M.
Published: February 2020

The analytical methods for the determination of the amine solvent properties do not provide input data for real-time process control and optimization and are labor-intensive, time-consuming, and impractical for studies of dynamic changes in a process. In this study, the potential of nondestructive determination of amine concentration, CO2 loading, and water content in CO2 absorption solvent in the gas processing unit was investigated through Fourier transform near-infrared (FT-NIR) spectroscopy that has the ability to readily carry out multicomponent analysis in association with multivariate analysis methods. The FT-NIR spectra for the solvent were captured and interpreted by using suitable spectra wavenumber regions through multivariate statistical techniques such as partial least square (PLS). The calibration model developed for amine determination had the highest coefficient of determination (R2) of 0.9955 and RMSECV of 0.75%. CO2 calibration model achieved R2 of 0.9902 with RMSECV of 0.25% whereas the water calibration model had R2 of 0.9915 with RMSECV of 1.02%. The statistical evaluation of the validation samples also confirmed that the difference between the actual value and the predicted value from the calibration model was not significantly different and acceptable. Therefore, the amine, CO2, and water models have given a satisfactory result for the concentration determination using the FT-NIR technique. The results of this study indicated that FT-NIR spectroscopy with chemometrics and multivariate technique can be used for the CO2 solvent monitoring to replace the time-consuming and labor-intensive conventional methods.
Use of Ex Vivo Patient-Derived Tumor Organotypic Spheroids to Identify Combination Therapies for HER2 Mutant Non–Small Cell Lung Cancer
Authors: Ivanova Elena , Kuraguchi Mari , Xu Man , Portell Andrew J. , Taus Luke , Diala Irmina , Lalani Alshad S. , Choi Jihyun , Chambers Emily S. , Li Shuai , Liu Shengwu , Chen Ting , Barbie Thanh U. , Oxnard Geoffrey R. , Haworth Jacob J. , Wong Kwok-Kin , Dahlberg Suzanne E. , Aref Amir A. , Barbie David A. , Bahcall Magda , Paweletz Cloud P. , Jänne Pasi A.
Published: February 2020

Purpose:

Evaluating drug responses using primary patient-derived cells ex vivo represents a potentially rapid and efficient approach to screening for new treatment approaches. Here, we sought to identify neratinib combinations in HER2 mutant non–small cell lung cancer (NSCLC) patient xenograft-derived organotypic spheroids (XDOTS) using a short-term ex vivo system.

Experimental Design:

We generated two HER2-mutant NSCLC PDX models [DFCI359 (HER2 exon19 755_757LREdelinsRP) and DFCI315 (HER2 exon20 V777_G778insGSP)] and used the PDX tumors to generate XDOTS. Tumor spheroids were grown in a microfluidic device and treated ex vivo with neratinib-based drug combinations. Live/dead quantification was performed by dual-labeling deconvolution fluorescence microscopy. The most efficacious ex vivo combination was subsequently validated in vivo using the DFCI359 and DFCI315 PDXs and a HER2YVMA genetically engineered mouse model.

Results:

Both neratinib and afatinib, but not gefitinib, induced cell death in DFCI359 XDOTS. The combinations of neratinib/trastuzumab and neratinib/temsirolimus enhanced the therapeutic benefit of neratinib alone in DFCI315 and DFCI359. The combination of neratinib and trastuzumab in vivo was more effective compared with single-agent neratinib or trastuzumab and was associated with more robust inhibition of HER2 and downstream signaling.

Conclusions:

The XDOTS platform can be used to evaluate therapies and therapeutic combinations ex vivo using PDX tumors. This approach may accelerate the identification and clinical development of therapies for targets with no or few existing models and/or therapies.
Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
Authors: Figlin Robert A. , Tannir Nizar M. , Uzzo Robert G. , Tykodi Scott S. , Chen David Y.T. , Master Viraj , Kapoor Anil , Vaena Daniel , Lowrance William , Bratslavsky Gennady , DeBenedette Mark , Gamble Alicia , Plachco Ana , Norris Marcus S. , Horvatinovich Joe , Tcherepanova Irina Y. , Nicolette Charles A. , Wood Christopher G.
Published: February 2020

Purpose:

Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC).

Patients and Methods:

Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS.

Results:

Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date.

Conclusions:

Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.
In VivoTracking of Adoptively Transferred Natural Killer Cells in Rhesus Macaques Using 89Zirconium-Oxine Cell Labeling and PET Imaging
Authors: Sato Noriko , Stringaris Kate , Davidson-Moncada Jan K. , Reger Robert , Adler Stephen S. , Dunbar Cynthia , Choyke Peter L. , Childs Richard W.
Published: February 2020

Purpose:

Trials of adoptive natural killer (NK)-cell immunotherapy for hematologic malignancies have thus far shown only marginal effects, despite the potent in vitro antitumor activity of these cells. Homing of infused cells to tumor microenvironments is critical for efficacy, but has not been well characterized. We established a novel method to track and quantify the distribution of adoptively transferred NK cells using rhesus macaques (RM) as a clinically relevant preclinical model.

Experimental Design:

RM NK cells were expanded ex vivo for 14–21 days, labeled with 89Zr-oxine complex, and assessed for phenotype, function, and survival. Trafficking of 89Zr-labeled ex vivo–expanded NK cells infused into RMs was monitored and quantitated by serial positron emission tomography (PET)/CT (n = 3, 2.05 ± 0.72 MBq, 23.5 ± 2.0 × 106 NK cells/kg) and compared with that of 89Zr-labeled nonexpanded NK cells, apoptotic NK cells, and hematopoietic stem and progenitor cells (HSPC).

Results:

NK cells retained sufficient levels of 89Zr for accurate in vivo tracking for 7 days. 89Zr labeling did not alter cellular phenotype, viability, or function. PET/CT showed NK cells initially localized in the lungs, followed by their migration to the liver, spleen, and, at low levels, bone marrow. One day following transfer, only 3.4% of infused NK cells localized to the BM versus 22.1% of HSPCs. No clinical side effects were observed, and dosimetry analysis indicated low organ radioexposures of 6.24 mSv/MBq (spleen) or lower.

Conclusions:

These data support translation of this technique to humans to track the distribution of adoptively infused cells and to develop novel techniques to improve immune cell homing to tumor microenvironments.
Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14–Mutant NSCLC
Authors: Recondo Gonzalo , Bahcall Magda , Spurr Liam F. , Che Jianwei , Ricciuti Biagio , Leonardi Giulia C. , Lo Ying-Chun , Li Yvonne Y. , Lamberti Giuseppe , Nguyen Tom , Milan Marina S.D. , Venkatraman Deepti , Umeton Renato , Paweletz Cloud P. , Albayrak Adem , Cherniack Andrew D. , Price Kristin S. , Fairclough Stephen R. , Nishino Mizuki , Sholl Lynette M. , Oxnard Geoffrey R. , Jänne Pasi A. , Awad Mark M.
Published: February 2020

Purpose:

Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors (TKI) are poorly understood. We aimed to characterize the genomic mechanisms of resistance to type I and type II MET TKIs and their impact on sequential MET TKI therapy outcomes in patients with metastatic MET exon 14–mutant NSCLC.

Experimental Design:

Genomic alterations occurring at the time of progression on MET TKIs were studied using plasma and tissue next-generation sequencing (NGS).

Results:

A total of 20 patients had tissue or plasma available for analysis at the time of acquired resistance to a MET TKI. Genomic alterations known or suspected to be mechanisms of resistance were detected in 15 patients (75%). On-target acquired mechanisms of resistance, including single and polyclonal MET kinase domain mutations in codons H1094, G1163, L1195, D1228, Y1230, and high levels of amplification of the MET exon 14–mutant allele, were observed in 7 patients (35%). A number of off-target mechanisms of resistance were detected in 9 patients (45%), including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF; one case displayed both on- and off-target mechanisms of resistance. In 2 patients with on-target resistant mutations, switching between type I and type II MET TKIs resulted in second partial responses.

Conclusions:

On-target secondary mutations and activation of bypass signaling drive resistance to MET TKIs. A deeper understanding of these molecular mechanisms can support the development of sequential or combinatorial therapeutic strategies to overcome resistance.
Not Yet Another Negative Trial–ReACTing on Recent Glioblastoma Trials
Authors: Wick Wolfgang , Wagener Robin J.
Published: February 2020

The present ReACT trial provides data from a small randomized controlled vaccination trial that in addition to other recent immunotherapy trials in glioblastoma allows sketching a rational, advanced trial design for the development of (immune) therapies in glioblastoma elaborating on but not restricting to biological monitoring and endpoints.

See related article by Reardon et al., p. 1586
Acoustic Analysis of Voice and Speech in Men with Skeletal Class III Malocclusion: A Pilot Study
Authors: Viegas Flávia , Viegas Danieli , Serra Guimarães Glaucio , Ritto Fabio , Simões-Zenari Marcia , Nemr Katia
Published: February 2020

Objectives: To assess the fundamental (f0) and first third formant (F1, F2, F3) frequencies of the 7 oral vowels of Brazilian Portuguese in men with skeletal class III malocclusion and to compare these measures with a control group of individuals with Angle’s class I. Methods: Sixty men aged 18–40 years, 20 with Angle’s class III skeletal malocclusion and 40 with Angle’s class I malocclusion were selected by speech therapists and dentists. The speech signals were obtained from sustained vowels, and the values of f0 and frequencies of F1, F2 and F3 were estimated. The differences were verified through Student’s t test, and the effect size calculation was performed. Results: In the class III group, more acute f0 values were observed in all vowels, higher values of F1 in the vowels [a] and [ε] and in F2 in the vowels [a], [e] and [i] and lower F1 and F3 values of the vowel [u]. Conclusion: More acute f0 values were found in all vowels investigated in the class III group, which showed a higher laryngeal position in the production of these sounds. The frequencies of the first 3 formants showed punctual differences, with higher values of F1 in the vowels [a] and [ε] and of F2 in [a], [e] and [i], and lower values of F1 and F3 in the vowel [u] in the experimental group. Thus, it is concluded that the fundamental frequency of the voice was the main parameter that differentiated the studied group from the control.
Protecting Interests of Animals in Custody Disputes: Italian Caselaw Outpaces Italian and European Union Legislation
Authors: Fossati Paola
Published: February 2020

People who live with pets (companion animals) in many cases see their pets as family members. Yet, in the eyes of the law, pets are still considered personal property. This is relevant to pet custody matters that may arise at the time of divorce or separation; pets fall within divorce financial proceedings. However, they have the unique nature of living and sentient property, which has interests. In this perspective, the best interest of the nonhuman animal should always be taken into account. Nonetheless, the law lacks definitive standards, and the ways in which courts construe contractual disputes involving nonhuman animals that relate to custody disputes in marital or other relationships do not always take into consideration the unique nature of this living and sentient property. This article provides an examination of the current Italian legal system and of Italian case law related to this matter.
Engaging Disenfranchised Youth through an Equine Assisted Activities Program: Understanding Psychosocial Benefits of Horse-Human Interactions
Authors: Norwood Michael Francis , Lakhani Ali , Kendall Elizabeth , Fullagar Simone , Maujean Annick
Published: February 2020

Evidence suggests equine-assisted activities may provide psychological benefits to young people “at-risk.” Results are presented from an equine program among 14- to 16-year-old children (N = 7), mostly boys (N = 6), attending a non-traditional flexi-school in Australia. Thematic analyses were undertaken on observations by facilitators, researchers, and a school teacher, and interviews with a school teacher. Key themes suggest that program participants benefited from positive engagement, social connectedness, and increased confidence, relationships, and attachment. Mechanisms were identified as a desire and an ability to connect with the horse and a positive environment. The social context of the equine program contrasts with other contexts in these young people’s lives, which allowed them to engage through more positive relational, affectionate behavior. For the boys, positive rather than damaging masculine behavior was displayed. Furthermore, the compatible student-environment interactions provide a backdrop which makes other positive changes possible.
Abundance and diversity of plant-parasitic nematodes associated with watermelon in Nigeria, with focus on Meloidogyne spp.
Authors: Bello Tesleem T. , Coyne Danny L. , Rashidifard Milad , Fourie Hendrika
Published: February 2020

Little information is available for nematode pests associated with watermelon in sub-Saharan Africa (SSA). This study recorded the abundance and prevalence of plant-parasitic nematodes from 25 localities across south-west Nigeria during 2016/2017. Of the 11 nematode species identified, those belonging to Meloidogyne spp. were predominant according to Prominence Values, followed by Helicotylenchus dihystera, Pratylenchus zeae and Scutellonema bradys. Morphological and molecular analyses revealed the identity of four species of root-knot nematodes: Meloidogyne enterolobii, M. incognita, M. javanica and M. arenaria (in descending order of abundance and occurrence). Meloidogyne arenaria is reported for the first time from south-west Nigeria, while S. bradys and Xiphinema nigeriense are first reports for watermelon. Significant associations were observed between the frequency of occurrence of the predominant nematode species and soil properties as well as rainfall. Results provide baseline information on the nematode pest occurrence on watermelon in Nigeria and in a wider context for SSA.
Borrowed Color and Flora/Fauna Terminology in Northwest New Guinea
Authors: Gasser Emily
Published: February 2020

The northwestern part of the island of New Guinea has been the site of intense contact between a hugely diverse set of languages. Languages from at least nine non-Austronesian families (plus several isolates) are spoken alongside Austronesian languages from the South Halmahera-West New Guinea branch, which arrived in the region roughly 3500 years ago. This paper looks at lexical items in the semantic areas of flora, fauna, and color terms and catalogues apparent loans between 52 of these languages, some relatively widespread (‘crocodile’, ‘chicken’, ‘dog’) and some much more limited in their scope. So far as the direction of borrowing can be established, the patterns of shared forms indicate ongoing lexical transfer across the region with a strong preference for Austronesian-to-Papuan borrowing, suggesting a historical pattern of Austronesian cultural influence in the region.