bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on a Four-Dimensional Evaluation Indicator System for Eco-Civilization Construction: A Case Study of Guangdong Province in China
Authors: WANG Wenjun , WANG Wenxiu , WU Dalei , SHI Baoya , ZHAO Daiqing
Published: January 2019

The report of the 18th National Congress of the Communist Party of China included the construction of ecological civilization in the “Five-in-One” (economic, political, cultural, social, and ecological progress) general layout for socialism with Chinese characteristics. Based on the concept of ecological civilization, the authors build an evaluation indicator system from four dimensions, namely ecological economy, ecological society, resource and environment efficiency, and ecological culture and institutions, including 45 basic indicators of three levels. In order to test the validity and reliability of the indicator system, the paper uses 21 prefecture-level cities in Guangdong Province as examples to evaluate the comprehensive level of eco-civilization construction and the statuses of the four dimensions by the attribute hierarchy model. The evaluation results show various statuses and characteristics of cities in Guangdong Province. The cities of Shenzhen, Dongguan, Shaoguan, Guangzhou and Maoming are notable in ecological economy; Shenzhen, Guangzhou, Zhongshan, Zhuhai and Huizhou are prominent in ecological society; Heyuan, Zhaoqing, Shaoguan, Qingyuan and Meizhou are the top five cities with relatively high resource and environment efficiency; Foshan, Guangzhou, Shenzhen, Zhuhai and Shantou are the first five cities that perform well in ecological culture and institutions. The evaluation results are consistent with the actual situation of Guangdong Province, indicating the high reliability and validity of the four-dimensional evaluation indicator system for eco-civilization construction.
GeoSim 2018 workshop report the 1st ACM SIGSPATIAL international workshop on geospatial simulation
Authors: Kim Joon-Seok , Kavak Hamdi , Züfle Andreas , Crooks Andrew , Manzoor Umar , Torrens Paul M.
Published: January 2019

Geospatial simulation is a powerful tool for many disciplines including urban analytics, social science and meteorology to understand, explain, and predict overly complex natural and human-made systems. For instance, hurricane simulation has been used to predict hurricane paths and to make a decisions such as evacuation plans. Traffic simulation have enabled us to forecast traffic congestion in cities around the world.
On the analysis of biomedical signals for disease classification
Authors: Vizza Patrizia , Tradigo Giuseppe
Published: January 2019

The analysis of biomedical signals and images is relevant for early diagnosis, detection and treatment of diseases. It represents the first step in the proper management of pathological conditions. Therefore, it is essential to support clinical practice during the diagnosis process by extracting relevant information and by classifying different diseases. This contribution outlines the methodologies of the most frequently used analysis techniques in biomedicine and their applications. The aim is to report about typical biosignals and bioimages and their analysis to enhance the importance of signal processing in the study and classification of specific diseases.
Causes and Patterns of Dementia: An Update in the Era of Redefining Alzheimer's Disease
Authors: James Bryan D. , Bennett David A.
Published: January 2019

The burden of dementia continues to increase as the population ages, with no disease-modifying treatments available. However, dementia risk appears to be decreasing, and progress has been made in understanding its multifactorial etiology. The 2018 National Institute on Aging–Alzheimer's Association (NIA-AA) research framework for Alzheimer's disease (AD) defines AD as a biological process measured by brain pathology or biomarkers, spanning the cognitive spectrum from normality to dementia. This framework facilitates interventions in the asymptomatic space and accommodates knowledge that many additional pathologies (e.g., cerebrovascular) contribute to the Alzheimer's dementia syndrome. The framework has implications for how we think about risk factors for “AD”: Many commonly accepted risk factors are not related to AD pathology and would no longer be considered risk factors for AD. They may instead be related to other pathologies or resilience to pathology. This review updates what is known about causes, risk factors, and changing patterns of dementia, addressing whether they are related to AD pathology/biomarkers, other pathologies, or resilience.
Influence Zone Division and Risk Assessment of Underwater Tunnel Adjacent Constructions
Authors: Zhou Zhong , Gao Wenyuan , Liu Zhuangzhuang , Zhang Chengcheng
Published: January 2019

Compared with ordinary tunnels, the influence analysis of underwater tunnel adjacent constructions is more complicated. At present, the empirical method used to divide the influence zone of the tunnel adjacent constructions has great uncertainty. So it is of great significance for actual construction and design to determine the influence zone accurately according to theoretical calculations. In this paper, based on the Hoek–Brown nonlinear failure criterion of rock mass and taking seepage factor into account, the stress state of rock mass around the underwater tunnel adjacent constructions can be deduced by elastoplastic theory. Then combined with the concept of “loose zone‐bearing zone”, the influence zone division method of underwater tunnel adjacent constructions is proposed, and it is applied to the analysis of engineering examples. Through the deduced theoretical formulas, the influence zone of underwater tunnel adjacent construction can be divided into extensively strong, strong, relatively strong, weak, and noninfluence zones. Corresponding the influence zones with the risk levels in the code, different control measures are adopted for different risk levels, which can provide certain guidance for the design and construction of tunnel in practical engineering.
Research on Differential Metabolites in Distinction of Rice (Oryza sativa L.) Origin Based on GC-MS
Authors: Feng Yuchao , Fu TianXin , Zhang Liyuan , Wang Changyuan , Zhang Dongjie
Published: January 2019

The analytical method for the metabolomics of the 60 rice seeds from two main rice origins in Heilongjiang Province was developed based on gas chromatography coupled with mass spectrum. The specific differential metabolites between two rice origins were identified, and the distinguish of the two main origins was illustrated by using the R software platform with XCMS software package for gas chromatography coupled with mass spectrum data processing, combined with multivariate statistical analysis software. The result indicated that the 173 peaks were detected, and 54 of which were structurally identified, covering amino acids, aliphatic acid, sugar, polyols, and so on. By comparing the data of Wuchang and Jiansanjiang origins, it was found that there were 9 special metabolites in Wuchang origin and 8 special metabolites in Jiansanjiang origin. The 10 differential metabolites with significant changes (P<0.05, VIP ≥ 1) were filtrated. It is indicated that the differential metabolites of rice carry information of their origin and there are the differences in the metabolites of rice in two main origins. The proposed method is expected to be useful for the metabolomic researches of rice.
Detecting Happiness Using Hyperspectral Imaging Technology
Authors: Hao Min , Liu Guangyuan , Gokhale Anu , Xu Ya , Chen Rui
Published: January 2019

Hyperspectral imaging (HSI) technology can be used to detect human emotions based on the power of material discrimination from their faces. In this paper, HSI is used to remotely sense and distinguish blood chromophores in facial tissues and acquire an evaluation indicator (tissue oxygen saturation, StO2) using an optical absorption model. This study explored facial analysis while people were showing spontaneous expressions of happiness during social interaction. Happiness, as a psychological emotion, has been shown to be strongly linked to other activities such as physiological reaction and facial expression. Moreover, facial expression as a communicative motor behavior likely arises from musculoskeletal anatomy, neuromuscular activity, and individual personality. This paper quantified the neuromotor movements of tissues surrounding some regions of interest (ROIs) on smiling happily. Next, we selected six regions—the forehead, eye, nose, cheek, mouth, and chin—according to a facial action coding system (FACS). Nineteen segments were subsequently partitioned from the above ROIs. The affective data (StO2) of 23 young adults were acquired by HSI while the participants expressed emotions (calm or happy), and these were used to compare the significant differences in the variations of StO2 between the different ROIs through repeated measures analysis of variance. Results demonstrate that happiness causes different distributions in the variations of StO2 for the above ROIs; these are explained in depth in the article. This study establishes that facial tissue oxygen saturation is a valid and reliable physiological indicator of happiness and merits further research.
Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa Essential Oils: Chemical Composition, Antimicrobial and Antileishmanial Activity
Authors: Teles Amanda Mara , Rosa Taynan Dulce da Silva , Mouchrek Adenilde Nascimento , Abreu-Silva Ana Lucia , Calabrese Kátia da Silva , Almeida-Souza Fernando
Published: January 2019

The resistance mechanisms of bacteria and protozoans have evidenced the need of discover new compounds with potential pharmaceutical activity against pathogenic microorganisms. Medicinal plants have been for centuries a promising alternative as sources of new drugs. The objective of this work was to evaluate the chemical composition, antimicrobial and antileishmanial activities of Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa essential oils. Chemical analysis was performed by gas chromatography-mass spectrometry. Antimicrobial activity was performed by disk diffusion and minimum inhibitory concentration (MIC) test. Antileishmanial activity was performed against antipromastigote and intracellular amastigote of Leishmania amazonensis. Cytotoxic and nitrite production were realized in BALB/c peritoneal macrophages. The major compounds of the essential oils were cinnamic aldehyde (46.30%) in C. zeylanicum, cis-p-menth-2-en-1-ol (33.88%) and linalyl acetate (13.90%) in O. vulgare, and turmerone (55.43%) in C. longa. The MIC showed significant antimicrobial activity of C. longa essential oil against S. aureus (83.3 ± 14.43 µg/mL). Antipromastigote activity showed IC50 values >500 µg/mL to C. zeylanicum, 308.4 ± 1.402 µg/mL to O. vulgare, and 405.5 ± 1.119 µg/mL to C. longa essential oil. Activity against intracellular amastigote of L. amazonensis showed IC50 of 63.3 ± 1.369 µg/mL and cytotoxic was not observed, resulting in selectivity index higher than 15.79 to parasite. C. longa essential oil decreased nitrite production in peritoneal macrophages, but not in Leishmania-infected cells. The chemical composition of the three essential oils is directly associated to its potential biological action, as the antimicrobial activity. C. longa presented a potent antileishmanial activity against promastigote and intracellular amastigote of L. amazonensis, although this activity is not linked to nitric oxide, since C. longa essential oil inhibits its production.
“Turn-On” Fluorescent Assay of Biothiols Based on Nitrogen-Rich Polymer Carbon Nanostrips and Its Application in Cell Imaging
Authors: Meng Xiangying , Qiao Jinjuan , Zhao Ronglan , Chu Hairong , Wang Ying , Chen Xiangyu , Yi Zhengjun
Published: January 2019

In this work, a sensitive and selective turn-on fluorimetric method has been developed for the determination of biothiols based on blocking Ag+-induced fluorescence quenching of nitrogen-rich polymer carbon nanostrips (NRPCNSs). Ag+ion can induce the fluorescence quenching of NRPCNSs due to the formation of nonfluorescent coordination complexes via robust Ag-N interaction. Once addition of biothiols, such as cysteine (Cys) and glutathione (GSH), Ag+ions prefer to interact with biothiols rather than NRPCNSs, which could be attribute to the formation of Ag-S bond, thus leading to effective fluorescent recovery of NRPCNSs. Under the optimized conditions, excellent linear relationships existed between the recovery degree of the NRPCNSs and the concentrations of Cys and GSH in the range of 0.05 μM to 10 μM and 0.2 μM to 30 μM, respectively. And, the limits of detection (LODs) for Cys and GSH are 16.5 nM and 65.1 nM, respectively. The detection system also shows high selectivity against other non-thiol amino acids. Moreover, the potential in practical applications of this proposed method has been demonstrated by detecting biothiols in human serum and fluorescence imaging of biothiols in living cells.
PDE5A Suppresses Proteasome Activity Leading to Insulin Resistance in C2C12 Myotubes
Authors: Liu Wei , Tian Xiaojun , Wu Ti , Liu Le , Guo Yanghongyun , Wang Changhua
Published: January 2019

Objective. The involvement of phosphodiesterase type 5 (PDE5) in the development of insulin resistance has been reported recently. However, the underlying molecular mechanism remains unclear. The present study aims at investigating the potential impacts of PDE5A on insulin signaling in C2C12 skeletal muscle myotubes and uncover the related mechanism. Methods. C2C12 myoblasts were differentiated into myotubes. Western blot was performed to detect the levels of proteins and phosphorylated proteins. Glucose uptake was determined by a colorimetric kit. The overexpression or knockdown of specific protein was carried out by infecting the myotubes with adenoviruses carrying cDNA or shRNA corresponding to the targeted protein, respectively. Results. PDE5A was demonstrated to negatively regulate insulin signaling, evidenced by the opposite effects on the suppression or enhancement of the insulin-stimulated Akt phosphorylation and 2-deoxy-D-glucose (2-DG) uptake in C2C12 myotubes, when PDE5A was overexpressed or knockdown, respectively. Interestingly, PDE5A overexpression led to significantly enhanced, while its knockdown resulted in markedly reduced, endoplasmic reticulum (ER) stress. Inhibition of ER stress improved PDE5A overexpression-induced insulin resistance. In addition, PDE5A was found to suppress proteasome activity. Inhibition of PDE5 by its selective inhibitor icariin restored PDE5A overexpression-reduced proteasome activity and mitigated PDE5A overexpression-induced ER stress. Consistently, icariin administration also markedly attenuated the detrimental impacts of PDE5A overexpression on insulin signaling. Conclusions. These results suggest that PDE5A suppresses proteasome activity, which results in ER stress and subsequent insulin resistance in C2C12 myotubes.
Effects of the Sharing Economy on Sequential Innovation Products
Authors: Liu Zhenfeng , Feng Jian , Wang Jinfeng
Published: January 2019

The emergence of the sharing economy has affected consumers and traditional manufacturers. We focus on product sharing and analyze its impacts on the manufacturer that offers sequential innovation products. We develop a two‐period model in which a monopoly manufacturer sells an old product and introduces a new product in each period; in the same period, an owner who bought a product for self‐use from the manufacturer in the previous period may rent the product out because of the low self‐use value in this period. Our analysis reveals that the sharing market increases or decreases the manufacturer’s profit, and this is mainly determined by the moral hazard cost and the salvage value of sharing products. Furthermore, the sharing market has an insignificant effect on the upgrading of products, but there is a bumping‐down effect on old products’ sales. Finally, the effect of the sharing market on the revenue of the owner and the sharing platform mostly depends on the risk of moral hazard, and it also affects the manufacturer’s product rollover strategy.
An Experiment on the Use of Genetic Algorithms for Topology Selection in Deep Learning
Authors: Mattioli Fernando , Caetano Daniel , Cardoso Alexandre , Naves Eduardo , Lamounier Edgard
Published: January 2019

The choice of a good topology for a deep neural network is a complex task, essential for any deep learning project. This task normally demands knowledge from previous experience, as the higher amount of required computational resources makes trial and error approaches prohibitive. Evolutionary computation algorithms have shown success in many domains, by guiding the exploration of complex solution spaces in the direction of the best solutions, with minimal human intervention. In this sense, this work presents the use of genetic algorithms in deep neural networks topology selection. The evaluated algorithms were able to find competitive topologies while spending less computational resources when compared to state-of-the-art methods.
Acute Pancreatitis after Colonoscopy: A Case Presentation and Literature Review
Authors: Doshi Sahil D. , Alvarez Yelina , Kumar Shria , Pickett-Blakely Octavia
Published: January 2019

We report a case of acute pancreatitis after an elective screening colonoscopy. A 51-year-old male with a left ventricular assist device for end-stage nonischemic cardiomyopathy and a family history of colorectal cancer was admitted for an expedited heart transplant evaluation. He underwent screening colonoscopy during this admission which was technically uncomplicated apart from requiring slight maneuvering at the splenic flexure. The following day, the patient developed acute epigastric pain and one episode of emesis. Subsequent laboratory evaluation revealed a significantly elevated lipase level and cross-sectional imaging consistent with acute pancreatitis. With no evidence of gallstones, alcohol use, and hypertriglyceridemia, the acute pancreatitis was deemed to be a complication of colonoscopy. The presumed mechanism of the pancreatitis was due to mechanical trauma from insufflation and abdominal pressure, applied to at the splenic flexure, which is in close proximity to the pancreatic tail. The patient was treated with supportive care (intravenous fluid, analgesia, and pancreatic rest) and improved significantly over a three-day period.
Utility of Real-Time and Retrospective Continuous Glucose Monitoring in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials
Authors: Ida Satoshi , Kaneko Ryutaro , Murata Kazuya
Published: January 2019

In the present study, we aimed to investigate the effects of continuous glucose monitoring (CGM) on blood glucose levels, body weight, blood pressure, and hypoglycaemia in patients with type 2 diabetes mellitus using a meta-analysis of randomized controlled trials (RCTs). A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. RCTs using CGM in patients with type 2 diabetes mellitus were then selected. Statistical analysis included calculation of the standardized mean difference (SMD) or risk ratio and 95% confidence intervals (CIs) using a random effects model. After literature search, seven RCTs (669 patients) satisfied the eligibility criteria established herein and were included into the meta-analysis. Compared with the self-monitoring blood glucose group, the CGM group exhibited significantly lower HbA1c levels (SMD, −0.35; 95% CI, −0.59–−0.10; P=0.006) and shorter time spent with hypoglycaemia (SMD, −0.42; 95% CI, −0.70–−0.13; P=0.004). Conversely, no differences in body weight and blood pressure were observed between the groups. CGM in patients with type 2 diabetes mellitus could reduce HbA1c levels and time spent with hypoglycaemia. However, because few RCTs were included in this present study and heterogeneity was also noted, care should be taken when interpreting the results.
Multiple Kernel Dimensionality Reduction via Ratio‐Trace and Marginal Fisher Analysis
Authors: Xu Hui , Yang Yongguo , Wang Xin , Liu Mingming , Xie Hongxia , Wang Chujiao
Published: January 2019

Traditional supervised multiple kernel learning (MKL) for dimensionality reduction is generally an extension of kernel discriminant analysis (KDA), which has some restrictive assumptions. In addition, they generally are based on graph embedding framework. A more general multiple kernel‐based dimensionality reduction algorithm, called multiple kernel marginal Fisher analysis (MKL‐MFA), is presented for supervised nonlinear dimensionality reduction combined with ratio‐race optimization problem. MKL‐MFA aims at relaxing the restrictive assumption that the data of each class is of a Gaussian distribution and finding an appropriate convex combination of several base kernels. To improve the efficiency of multiple kernel dimensionality reduction, the spectral regression frameworks are incorporated into the optimization model. Furthermore, the optimal weights of predefined base kernels can be obtained by solving a different convex optimization. Experimental results on benchmark datasets demonstrate that MKL‐MFA outperforms the state‐of‐the‐art supervised multiple kernel dimensionality reduction methods.
Flood Simulation by a Well-Balanced Finite Volume Method in Tapi River Basin, Thailand, 2017
Authors: Vichiantong Sutatip , Pongsanguansin Thida , Maleewong Montri
Published: January 2019

Flood simulation of a region in southern Thailand during January 2017 is presented in this work. The study area covers the Tapi river, the longest river in southern Thailand. The simulation is performed by applying the two-dimensional shallow water model in the presence of strong source terms to the local bottom topography. The model is solved numerically by our finite volume method with well-balanced property and linear reconstruction technique. This technique is accurate and efficient at solving for complex flows in the wet/dry interface problem. Measurements of flows are collected from two gauging stations in the area. The initial conditions are prepared to match the simulated flow to the measurements recorded at the gauging stations. The accuracy of the numerical simulations is demonstrated by comparing the simulated flood area to satellite images from the same period. The results are in good agreement, indicating the suitability of the shallow water model and the presented numerical method for simulating floodplain inundation.
Selected Office Based Anticancer Treatment Strategies
Authors: Stoff Jesse A.
Published: January 2019

Over the years, the treatment of patients with cancer has varied widely as much because of recent advancements in science and medicine as the philosophies that belie their use. This paper briefly describes many of the prevailing approaches in use today with an attempt to offer some perspective of how to apply these disparate methodologies so that they may be more effectively integrated, resulting in consistently better clinical responses.
Simulation Research on Safe Flow Rate of Bidirectional Crowds Using Bayesian‐Nash Equilibrium
Authors: Liao Can , Zhu Kejun , Guo Haixiang , Tang Jian
Published: January 2019

Current research on pedestrian flows has mainly focused on evacuation optimization during or after emergencies; however, crowd management before emergencies has received little attention. This paper examines the management of a Safe Pedestrian Flow Rate, in which the Bayesian‐Nash Equilibrium mimics pedestrians’ decision‐making, and a multiagent system is employed to reproduce pedestrians’ interactions. In the model, the pedestrian tunnel is divided into cells, with each pedestrian in a cell receiving a utility depending on the distance to the exit and the number of pedestrians in the cell. Then, each pedestrian uses the Bayesian‐Nash Equilibrium to search for the target cell with maximum expected utility, moves in, and makes next decision until exiting the tunnel. The simulation model is calibrated and validated from a real scenario. Finally, from the experimental data collected from different simulation scenarios, this research reaches the conclusion that the Safe Pedestrian Flow Rate increases by about 2.96ped/s as the tunnel width expanded by 1m. This paper offers a novel method for reducing potential losses caused by crowd emergencies and can be a valuable reference for managing pedestrian flows and designing public places.
Risk Factors for Cervical Lymph Node Metastasis of Papillary Thyroid Microcarcinoma: A Single-Center Retrospective Study
Authors: Cheng Feng , Chen Yanyan , Zhu Lei , Zhou Bin , Xu Yonghong , Chen Yiran , Wen Liping , Chen Shuzheng
Published: January 2019

Objective. To identify the clinicopathological features correlated to lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods. Clinical data of 785 PTMC patients who underwent surgical treatment at the Lishui Municipal Central Hospital from September 2008 to December 2017 were retrospectively analyzed. Clinical and pathological risk factors for lymph node metastasis (LNM), central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) were analyzed. Results. LNM was found in 236 (30.2%) patients. Multivariate logistic regression analysis revealed that in PTMC, male gender, age<55 years, tumor size>5 mm, bilateral lesions, and extrathyroidal extension were independent risk factors for LNM in general and for CLNM. For LLNM, tumor size>5 mm, multifocal lesions, and extrathyroidal extension were independent risk factors. Conclusions. Identification of risk factors for cervical LNM could assist individualization of clinical management for PTMC.
Amazonian Metakaolin Reactivity for Geopolymer Synthesis
Authors: Sá Ribeiro Ruy A. , Sá Ribeiro Marilene G. , Kutyla Gregory P. , Kriven Waltraud M.
Published: January 2019

To determine the viability of using a local resource for geopolymer synthesis, geopolymers were synthesized using metakaolin made from clay mined in the Amazonian region of Brazil. Samples were made with mixed potassium-sodium and pure sodium metakaolin-based geopolymer. Samples were also made using commercial metakaolin (CMK) from BASF, Inc. as a comparison to the Amazonian metakaolin (AMK). Scanning electron microscopy was used to investigate the microstructure of the materials. X-ray diffraction was able to confirm the formation of geopolymer. The mechanical properties of AMK material were nearly equivalent to those based on CMK. Neither CMK nor AMK reacted completely, although samples made with CMK showed less unreacted material. By increasing the mixing intensity and duration, the amount of residual unreacted material was substantially reduced, and mechanical properties were improved.
Pulmonary Edema Occurring after Nitric Acid Exposure
Authors: Meaden Christopher W. , Kashani John S. , Vetrano Stephen
Published: January 2019

Nitric acid (HNO3) is a strong acid and oxidizing agent used for various applications including production of ammonium nitrate in the fertilizer industry. Nitrogen oxides formed when nitric acid interacts with the environment have been implicated in inhalation injuries. This describes a case of a 49-year-old male who presented to the emergency department complaining of an acute onset of shortness of breath approximately 12 hours after being exposed to nitric acid fumes. He presented with a room air oxygen saturation of 80 percent with moderate to severe respiratory distress. His plain film chest radiograph showed bilateral pulmonary infiltrates and pulmonary edema. Over a seven-day hospital course, he had an improvement in his clinical status and chest X-ray with normal pulmonary function tests one month after discharge. Although exposure to the fumes of nitric acid is known to cause delayed pulmonary edema, it is rarely reported in the medical literature. This case serves as a reminder to consider exposure to fumes of nitric acid in a patient presenting with pulmonary edema and highlights the importance of obtaining a work history.
The Next Wave of Stroma-Targeting Therapy in Pancreatic Cancer
Authors: Huang Huocong , Brekken Rolf A.
Published: January 2019

The stroma of pancreatic ductal adenocarcinoma (PDA) forms a major barrier to therapy and immune surveillance. Elahi-Gedwillo and colleagues demonstrate that halofuginone has potent antifibrotic activity in PDA by directly inhibiting the activation of pancreatic stellate cells, thereby reducing the deposition of extracellular matrix components, including collagen and hyaluronic acid. As a result, halofuginone improves drug delivery and the infiltration of favorable immune cells such as immune-stimulatory myeloid cells and cytotoxic T cells. Despite recent controversies regarding targeting stroma in PDA, this study highlights that modifying the stroma of PDA remains an attractive strategy to improve the efficacy of therapy.

See related article by Elahi-Gedwillo et al., p. 372
Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes
Authors: Alatrash Gheath , Qiao Na , Zhang Mao , Zope Madhushree , Perakis Alexander A. , Sukhumalchandra Pariya , Philips Anne V. , Garber Haven R. , Kerros Celine , St. John Lisa S. , Khouri Maria R. , Khong Hiep , Clise-Dwyer Karen , Miller Leonard P. , Wolpe Steve , Overwijk Willem W. , Molldrem Jeffrey J. , Ma Qing , Shpall Elizabeth J. , Mittendorf Elizabeth A.
Published: January 2019

Purpose:

Inefficient homing of adoptively transferred cytotoxic T lymphocytes (CTLs) to tumors is a major limitation to the efficacy of adoptive cellular therapy (ACT) for cancer. However, through fucosylation, a process whereby fucosyltransferases (FT) add fucose groups to cell surface glycoproteins, this challenge may be overcome. Endogenously fucosylated CTLs and ex vivo fucosylated cord blood stem cells and regulatory T cells were shown to preferentially home to inflamed tissues and marrow. Here, we show a novel approach to enhance CTL homing to leukemic marrow and tumor tissue.

Experimental Design:

Using the enzyme FT-VII, we fucosylated CTLs that target the HLA-A2–restricted leukemia antigens CG1 and PR1, the HER2-derived breast cancer antigen E75, and the melanoma antigen gp-100. We performed in vitro homing assays to study the effects of fucosylation on CTL homing and target killing. We used in vivo mouse models to demonstrate the effects of ex vivo fucosylation on CTL antitumor activities against leukemia, breast cancer, and melanoma.

Results:

Our data show that fucosylation increases in vitro homing and cytotoxicity of antigen-specific CTLs. Furthermore, fucosylation enhances in vivo CTL homing to leukemic bone marrow, breast cancer, and melanoma tissue in NOD/SCID gamma (NSG) and immunocompetent mice, ultimately boosting the antitumor activity of the antigen-specific CTLs. Importantly, our work demonstrates that fucosylation does not interfere with CTL specificity.

Conclusions:

Together, our data establish ex vivo CTL fucosylation as a novel approach to improving the efficacy of ACT, which may be of great value for the future of ACT for cancer.
Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702)
Authors: Rahbar Habib , Zhang Zheng , Chenevert Thomas L. , Romanoff Justin , Kitsch Averi E. , Hanna Lucy G. , Harvey Sara M. , Moy Linda , DeMartini Wendy B. , Dogan Basak , Yang Wei T. , Wang Lilian C. , Joe Bonnie N. , Oh Karen Y. , Neal Colleen H. , McDonald Elizabeth S. , Schnall Mitchell D. , Lehman Constance D. , Comstock Christopher E. , Partridge Savannah C.
Published: January 2019

Purpose:

Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives.

Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure.

Results:

Of 107 women enrolled, 67 patients (median age 49, range 24–75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10−3 vs.1.47 × 10−3; P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65–0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10−3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%–31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10−3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers.

Conclusions:

DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.
Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis
Authors: Koo Jung-Hoon , Kang Eun-Bum , Cho Joon-Yong
Published: January 2019

Background: Mitochondrial dysfunction is implicated in the pathogenesis of multiple muscular diseases, including sporadic inclusion body myositis (s-IBM), the most common aging-related muscle disease. However, the factors causing mitochondrial dysfunction in s-IBM are unknown. Objective: We hypothesized that resistance exercise (RE) may alleviate muscle impairment by improving mitochondrial function via reducing amyloid-beta (Aβ) accumulation. Methods: Twenty-four male Wistar rats were randomized to a saline-injection control group (sham, n = 8), a chloroquine (CQ) control group (CQ-CON, n = 8), and a CQ plus RE group (CQ-RE, n = 8) in which rats climbed a ladder with weight attached to their tails 9 weeks after starting CQ treatment. Results: RE markedly inhibited soleus muscle atrophy and muscle damage. RE reduced CQ-induced Aβ accumulation, which resulted in decreased formation of rimmed vacuoles and mitochondrial-mediated apoptosis. Most importantly, the decreased Aβ accumulation improved both mitochondrial quality control (MQC) through increased mitochondrial biogenesis and mitophagy, and mitochondrial dynamics. Furthermore, RE-mediated reduction of Aβ accumulation elevated mitochondrial oxidative capacity by upregulating superoxide dismutase-2, catalase, and citrate synthase via activating sirtuin 3 signaling. Conclusion: RE enhances mitochondrial function by improving MQC and mitochondrial oxidative capacity via reducing Aβ accumulation, thereby inhibiting CQ-induced muscle impairment, in a rat model of s-IBM.
Isolating Chromosomes of the Komodo Dragon: New Tools for Comparative Mapping and Sequence Assembly
Authors: Iannucci Alessio , Altmanová Marie , Ciofi Claudio , Ferguson-Smith Malcolm , Pereira Jorge C. , Rehák Ivan , Stanyon Roscoe , Velenský Petr , Rovatsos Michail , Kratochvíl Lukáš , Johnson Pokorná Martina
Published: January 2019

We developed new tools to build a high-quality chromosomal map of the Komodo dragon (Varanus komodoensis) available for cross-species phylogenomic analyses. First, we isolated chromosomes by flow sorting and determined the chromosome content of each flow karyotype peak by FISH. We then isolated additional Komodo dragon chromosomes by microdissection and amplified chromosome-specific DNA pools. The chromosome-specific DNA pools can be sequenced, assembled, and mapped by next-generation sequencing technology. The chromosome-specific paint probes can be used to investigate karyotype evolution through cross-species chromosome painting. Overall, the set of chromosome-specific DNA pools of V. komodoensis provides new tools for detailed phylogenomic analyses of Varanidae and squamates in general.
Alfredo Volpi
Authors: Monteiro Taís Cabral
Published: January 2019

Este ensaio dedicado a Alfredo Volpi teve início durante as pesquisas para a tese de doutorado Percursos poéticos. É pautado nas entrevistas concedidas pelo artista e em textos históricos no âmbito da arte moderna. Torna-se notável como a particularidade dos discursos do artista permite maior aproximação do contexto original no qual se desenvolveram os seus trabalhos. Desse modo, os depoimentos pessoais e práticas pictóricas levam a uma interpretação poética das obras, tendo as cidades como espaço processual da atividade artística: o percurso criativo do artista relaciona-se com a vivência e as viagens no Brasil, em São Paulo e Mogi das Cruzes, e em cidades da Itália.
Nietzsche e Villa-Lobos: da música dionisíaca à canção folclórica
Authors: Lima Márcio José Silveira
Published: January 2019

O artigo expõe aspectos da concepção de Nietzsche sobre a música dionisíaca, tentando apontar para possíveis convergências com a estética do compositor Villa-Lobos, cujas composições foram marcadas pela utilização de temáticas e escalas folclóricas. Trata-se de compreender a música dionisíaca em sua relação com a mitologia, defendendo que a noção de cultura trágica que decorre dessa relação significa para Nietzsche uma possibilidade de superação dos valores cristalizados há séculos no Ocidente, tanto em termos morais, quanto musicais. De igual maneira, ao enfatizar a importância da canção folclórica para a linguagem musical, Villa-Lobos se insere num contexto de superação da linguagem musical dominada pela escala tonal, ao mesmo tempo em que utiliza de seus procedimentos estéticos para uma intensa inserção no debate cultural de sua época em torno da identidade nacional brasileira.

Palavras-chaveNietzsche; Villa-Lobos; Música; Canção Dionisíaca; Música Folclórica.
Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors
Authors: Nelson Christopher P. , Lai Florence Y. , Nath Mintu , Ye Shu , Webb Thomas R. , Schunkert Heribert , Samani Nilesh J.
Published: January 2019

Background:

Although short-term trials have suggested that PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are safe and reduce risk of cardiovascular diseases, their long-term safety is unclear. Genetic variants associated with lower activity of a gene can act as proxies to identify potential long-term side effects of drugs as recently exemplified by association of LDL (low-density lipoprotein)-lowering variants in the
HMGCR
(target for statins) and
PCSK9
genes with increased risk of type 2 diabetes mellitus (T2DM). However, analyses of the full spectrum of potential side effects of PCSK9 inhibition using a genetic approach have not been undertaken.

Methods:

We examined the association of an LDL-lowering variant in the
PCSK9
gene (T allele of rs1159147), as well as 2 LDL-lowering
HGCMR
variants (G allele of rs17238484 and T allele of rs12916) with 80 diseases and traits in up to 479 522 individuals in UK Biobank.

Results:

The
PCSK9
T allele was significantly (Bonferroni
P
<6.25×10
−4
) associated with risk of T2DM, increased body mass index, waist circumference, waist-hip ratio, diastolic blood pressure, type 1 diabetes mellitus, and insulin use. The
HMGCR
variants were also associated with risk of T2DM, although their previously reported associations with anthropometric traits were found to be confounded. Mediation analysis suggested that the association of the
PCSK9 T
allele with risk of T2DM but not diastolic blood pressure was largely independent of its association with body mass index and central obesity. Nominally significant associations of the
PCSK9 T
allele were also seen with peptic ulcer disease, depression, asthma, chronic kidney disease, and venous thromboembolism.

Conclusions:

Our findings support previous genetic analyses suggesting that long-term use of PCSK9 inhibitors, like statins, may be associated with increased risk of T2DM. Some other potential side effects need to be looked for in future studies of PCSK9 inhibitors, although we did not find signals that raise substantial concerns about their long-term safety.
Age-Related Differences in Time-Based Event Expectancies
Authors: Kunchulia Marina , Parkosadze Khatuna , Thomaschke Roland
Published: January 2019

The ability to form time-based event expectancies is one of the most important determinants of anticipative behavior. The aim of the present study was to determine whether healthy aging influences the formation of time-based event expectancies. Ten older adults with ages ranging between 60 and 73 years and ten younger adults with ages ranging between 20 and 32 years participated. We employed a binary choice response task mimicking a computer game, in which two target stimuli and two pre-target intervals appeared overall equally often. One of the targets was paired with the short interval and the other target with the long interval in 80% of the trials. Our results showed that younger adults responded more rapidly to frequent interval–target combinations than to infrequent combinations, suggesting that the young participants formed time-based event expectancies. In contrast, the ability to form time-based event expectancies was reduced for older participants. The formation of time-based event expectancies seems to change during healthy aging. We propose that this age-related difference is due to age-related expectation deficits or a reduction of attentional capacities, rather than to deficits in timing abilities.
Phyllostachys danxiashanensis (Poaceae: Bambusoideae), a new species from south China
Authors: ZHENG XI-RONG , TONG YI-HUA , NI JING-BO , CHEN ZAI-XIONG , XIA NIAN-HE
Published: January 2019

A new bamboo species, Phyllostachys danxiashanensis (Poaceae: Bambusoideae), is described from Danxia Mountain, Northern Guangdong. This new species is similar to P. rivalis in having papery culm sheaths, erect culm sheath blades and the absence of culm sheath auricles, but it differs from P. rivalis by its much longer cilia on culm sheath ligules, hispid culm sheaths, and fewer leaves on ultimate branches.
The orchid-bee fauna (Hymenoptera: Apidae) of a forest remnant in northeastern Brazil, with new geographic records and an identification key to the known species of the Atlantic Forest of northeastern Brazil
Authors: NEMÉSIO ANDRÉ
Published: January 2019

The orchid bee fauna of Estação Ecológica de Murici (ESEC Murici), in the state of Alagoas, one of the largest remnants of the Atlantic Rain Forest in northeastern Brazil, was surveyed for the first time. Seven hundred and twenty-one orchid-bee males belonging to 17 species were collected from the 3rd to the 10th of September, 2009. Besides the recently described Eulaema (Apeulaema) felipei Nemésio, 2010, three other species recorded at ESEC Murici deserve further attention: Euglossa amazonica Dressler, 1982b, recorded for the first time outside the Amazon Basin; Euglossa milenae Bembé, 2007 and Euglossa analis Westwood, 1840, both recorded for the first time in the Atlantic Forest of northeastern Brazil north to São Francisco river. These results together with previous samplings in the state of Alagoas reveal that at least 22 orchid-bee species are now known to occur there. Three other species not recorded for Alagoas yet are known from the neighbor states of Sergipe, Pernambuco, and Paraíba. An identification key to all 25 species of Euglossina known to occur in the states of Alagoas, Sergipe, Pernambuco, Paraíba, and Rio Grande do Norte is provided.
Validation of the status of a species with high CO1 and low nuclear genetic divergences: the scab mite Caparinia ictonyctis stat. res. (Acariformes: Psoroptidae) parasitizing the African hedgehog Atelerix albiventris
Authors: BOCHKOV ANDRE V. , KLIMOV PAVEL B. , KIM DA-HEE , SKORACKI MACIEJ
Published: January 2019

We report two host-specific lineages of scab mites of the genus Caparinia, parasitizing European and African hedgehogs. Based on morphology, these mite lineages are closely related sister groups. The morphological differences, however, are subtle and do not provide clear-cut evidence for the existence of separate species. CO1 divergence between these lineages was 7.4–7.8%, well above the CO1 barcoding gaps or thresholds commonly used to separate species, whereas divergence of five nuclear genes was very low, 0.06–0.53%, suggesting that these lineages could belong to a single species with gene flow between them. Thus, there is a conflict between the mitochondrial (CO1) gene and nuclear genes (i.e mito-nuclear discordance). We attribute this conflict to the ‘gray zone’ where species delimitation is ambiguous due to substantial gene flow. We also report another ‘gray zone’ species, Psoroptes ovis (a species of veterinary importance), whose within-species CO1 distances reached 6.0%. We provide a detailed morphological description and figures of C. ictonyctis stat. res. from the African hedgehog, using light and SEM microscopy and give morphometric data for this species and its sister species, Caparinia tripilis from Europe. For all known species of Caparinia, we document their host associations and give a key to species of the world based on results of our morphological and molecular analyses and a nearly exhaustive study of museum specimens.
Three new species of the pandalid shrimp genus Pandalopsis Spence Bate, 1888 (Crustacea: Decapoda: Caridea) from the southwestern Sea of Okhotsk, with supplemental note on P. glabra Kobjakova, 1936
Authors: KOMAI TOMOYUKI , HIBINO MAI
Published: January 2019

The present study deals with a collection of deep-sea shrimp of the pandalid genus Pandalopsis Spence Bate, 1888 from the Nemuro Strait, Hokkaido, southwestern part of the Sea of Okhotsk. Three new species are described and illustrated: Pandalopsis capillus n. sp., P. houyuu n. sp. and P. princeps n. sp. In addition, Pandalopsis glabra Kobjakova, 1936, a species endemic to the Sea of Okhotsk, is supplementary reported. Most specimens were collected from steep slopes or hard bottoms at depths greater than 400 m by commercial shrimp trap or gill nets operated by local fishermen. Differentiation of the new species is primarily based on a morphological comparison, supplemented by a preliminary genetic analysis of partial segments of the mitochondrial 16S rRNA gene. An identification key to the species of Pandalopsis is presented.
Description of immatures of Stolas aenea (Olivier, 1790) and Stolas nudicollis (Boheman, 1850) (Coleoptera: Chrysomelidae: Cassidinae: Mesomphaliini)
Authors: LEOCÁDIO MICHELE , MERMUDES JOSÉ RICARDO M.
Published: January 2019

Immature stages of Stolas aenea and S. nudicollis are described based on specimens collected in Rio de Janeiro, Brazil. Descriptions including chaetotaxy, illustrations and photographs (including SEM images) are given for eggs, first and last instar stages. New host plant records are presented for both species. This is the first detailed description for any species in the genus Stolas. Morphological comparisons with other Mesomphaliini species are provided.
A new species of the Hyalella ‘azteca’ complex (Crustacea: Amphipoda: Hyalellidae) from Florida
Authors: DRUMM DAVID T. , KNIGHT-GRAY JULIANNE
Published: January 2019

Examination of material from the Wakulla River in north-western Florida revealed the presence of a new species of the amphipod genus Hyalella. It appears to be most closely related to H. azteca (Saussure) sens. strict., but can be distinguished by the nature of maxilla 1 and the telson. The setation of uropod 3 has been given systematic importance for this genus, but we show in the present paper that this character exhibits high intraspecific variation, even within the same individual. This is the first formally described species of Hyalella from Florida.