bluuebunny/crossref_metadata_2025 huggingface dataset:
A redescription of the endemic antiarch placoderm
Asterolepis thule
from the Middle Devonian (Givetian) of Shetland and its biostratigraphical horizon
Authors: Newman Michael J. , Den Blaauwen Jan L.
Published: May 2018

The Givetian (Middle Devonian) antiarch
Asterolepis thule
was first described in 1932 and its stratigraphical horizon was poorly understood as were all the Devonian deposits in the SE of Shetland (South East Shetland Group). Since that time a greater understanding of the age of these deposits has been made. This, coupled with the greater clarity of the biostratigraphy of the Devonian of Scotland and its correlation with the Baltic Devonian, has allowed the species to be placed in a biostratigraphical zonation. The species is confined to Sumburgh Head and so appears endemic. Other species are also endemic and there are some relict fauna in the South East Shetland Group. This suggests that the South East Shetland Group fauna originated mostly in isolation to the main depositional areas of the Givetian in Scotland and elsewhere, although some species are more cosmopolitan.
2017 Meeting of the National Directors of Graduate Studies in Pharmacology and Physiology
Authors: Victor Tanya R. , Thompson Kaitlyn K. , Barnett Joey V. , Karpa Kelly D.
Published: May 2018

The National Directors of Graduate Studies biennial meeting is a forum for directors from pharmacology and physiology graduate programs to discuss challenges and best practices for programs that are preparing trainees to be successful in the biomedical workforce. The 2017 meeting was held on the campus of Stony Brook University in Stony Brook, NY. Over the course of the 3-day event, several themes evolved, including graduate education training and curricula, diversity and career development, and scientific rigor and communication. Overall, presentations and discussions highlighted the challenges and opportunities for training PhD biomedical scientists and featured best practices from across the country.
Who’s the boss: determining the control pathways of cardiovascular and cellular immune responses to acute stress
Authors: Edwards Kate M. , Morris Nathan B.
Published: May 2018

Acute stress responses are known to include increases in heart rate and blood pressure, as well as increases in the number of circulating immune cells, all of which are governed by the autonomic nervous system. This laboratory practical measures cardiovascular and circulating immune cell responses to a passive (cold pressor) and active (mental arithmetic) acute stress task in student participants. The results allow them to examine the different patterns of autonomic response they elicit (approximated by heart rate and blood pressure responses), and knowledge of these responses can then be used to infer the governing autonomic aspect of the increases in circulating immune cells from the results. This activity can be either adapted from teacher-led methods to inquiry, asking students to design the details of the acute stress tasks, or developed by asking students to design a follow-up experiment that could be used to provide direct evidence for their conclusions. Data collected provide a platform for teaching data analysis and interpretation, as well as critical thinking.
A survey of student engagement with multiple resources in an undergraduate physiology course: retrieve or look it up
Authors: Anderson Lisa C.
Published: May 2018

Retrieval practice, a deep-learning technique in which the learner attempts to recall a concept of interest from memory, has been shown to be more effective than surface-learning techniques, such as rereading a textbook. Accordingly, textbook publishers are developing supplemental resources that are purported to improve student learning outcomes by encouraging deep learning and critical thinking. The purpose of this study is to 1) survey students in a physiology course about their use of multiple course resources; and 2) assess the effect of self-reported engagement in course resources on learning outcomes, as assessed by comparing course grades. Students who had completed an undergraduate physiology course were sent an online survey about their course experience; two reminders were e-mailed. Students were asked to report their physiology course grade, satisfaction with how much they had learned, which resources they had used, and how they had completed course assignments (critical thinking exercises and online quizzes), i.e., whether they had 1) looked up answers online, 2) looked up answers in the textbook, 3) tried to figure out the answers before using the textbook, or 4) only used their recall. Categories 1 and 2 were considered nonretrieval strategies, and categories 3 and 4 were considered retrieval strategies. There was no association with the type of resource students used and course grade or course satisfaction. Students who practiced retrieval strategies achieved significantly higher course grades than students who did not for both critical thinking exercises and online quizzes.
Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people
Authors: Russell Ryan D. , Hu Donghua , Greenaway Timothy , Sharman James E. , Rattigan Stephen , Richards Stephen M. , Keske Michelle A.
Published: May 2018

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.
Dynamic Price Competition between a Macrocell Operator and a Small Cell Operator: A Differential Game Model
Authors: Romero Julián , Sanchis-Cano Angel , Guijarro Luis
Published: May 2018

An economic model was analyzed where a new supplier implements the technology of the small cells and positions itself as an incumbent service provider. This provider performs a dynamic reuse of resources to compete with the macrocells service provider. The model was analyzed using game theory as a two‐stage game. In the first stage, the service providers play a Stackelberg differential game where the price is the control variable, the existing provider is the leader, and the new supplier is the follower. In the second stage, users’ behavior is modeled using an evolutionary game that allows predicting the population changes with variable conditions. This paper contributes to the implementation of new technologies in the market of mobile communications through analysis of competition between the new small cell service providers (SSPs) and the existing service providers along with the users’ behavior of mobile communications. The result shows that users get a better service, SSP profits are guaranteed, and SSP entry improves users’ welfare and social welfare.
The Cost Management on the Quantification of Responsibility
Authors: Zhou Wenwen , Li Yuchen , Liu Hao , Song Xiaobo
Published: May 2018

Cost management is an important part of enterprise management and can enhance the competitiveness of enterprises and improve the sustainability of enterprise development. Responsibility management can maximize the enthusiasm and initiative of employees and effectively improves the efficiency of cost management. Quantitative responsibility is the premise of realizing responsibility management. Aiming at the problem of unclear responsibility for costs within the enterprise, a method for responsible quantification based on intuitionistic trapezoidal fuzzy numbers and genetic algorithms is proposed in this paper. This paper first expounds on a cost management structure model, uses the method of intuitionistic fuzzy mathematics to determine the initial value of the responsibility based the structure model, then constructs the quantitative model for the coefficient of responsibility, and finally uses a specific enterprise as an example of quantitative calculations to solve the responsibility problem.
Intelligent Method for Identifying Driving Risk Based on V2V Multisource Big Data
Authors: Peng Jinshuan , Shao Yiming
Published: May 2018

Risky driving behavior is a major cause of traffic conflicts, which can develop into road traffic accidents, making the timely and accurate identification of such behavior essential to road safety. A platform was therefore established for analyzing the driving behavior of 20 professional drivers in field tests, in which overclose car following and lane departure were used as typical risky driving behaviors. Characterization parameters for identification were screened and used to determine threshold values and an appropriate time window for identification. A neural network‐Bayesian filter identification model was established and data samples were selected to identify risky driving behavior and evaluate the identification efficiency of the model. The results obtained indicated a successful identification rate of 83.6% when the neural network model was solely used to identify risky driving behavior, but this could be increased to 92.46% once corrected by the Bayesian filter. This has important theoretical and practical significance in relation to evaluating the efficiency of existing driver assist systems, as well as the development of future intelligent driving systems.
Numerical Study on Crack Distributions of the Single‐Layer Building under Seismic Waves
Authors: Dong Fenghui , Zhong Zhipeng , Cheng Jin
Published: May 2018

This paper conducts a numerical simulation of the antiseismic performance for single‐layer masonry structures, completes a study on crack distributions and detailed characteristics of masonry structures, and finally verifies the correctness of the numerical model by experimental tests. This paper also provides a reinforced proposal to improve the antiseismic performance of single‐layer masonry structures. Results prove that the original model suffers more serious damage than the reinforced model; in particular, longitudinal cracks appear on bottoms of two longitudinal walls in the original model, while these cracks appear later in the reinforced model; a lot of cracks appear on the door hole of the original model, and no crack appears in the reinforced model till the end of seismic waves; seismic damage of walls in the reinforced model is obviously lighter than that in the original model; dynamic responses at all observed points of the reinforced masonry are obviously less than those of the original model. Strains at all positions of the reinforced model are obviously smaller than those of the original model. From macroscopic and microscopic perspectives, the computational results prove that the reinforced proposal proposed in this paper can effectively improve the antiseismic performance of the masonry structure.
Performance Evaluation of Jatropha and Pongamia Oil Based Environmentally Friendly Cutting Fluids for Turning AA 6061
Authors: Jeevan T. P. , Jayaram S. R.
Published: May 2018

Owing to the desirable properties of vegetable oils as cutting fluids, an attempt is made to explore the potentiality of plentifully available vegetable oils as a cutting fluid for turning AA 6061. Two nonedible vegetable oils, Jatropha and Pongamia, in their chemically modified (epoxidized) versions are used as straight cutting fluids. Cutting fluids are introduced to the machining zone with the aid of Minimal Quantity Lubrication (MQL) method. Taguchi’s technique of orthogonal arrays is used to develop an effective design of experiments. The results obtained under epoxidized versions of Jatropha and Pongamia oils are compared with the results of mineral oil in terms of cutting forces and surface roughness. Experimental observations and statistical analysis show that, compared to mineral oil, the modified versions of vegetable oil-based cutting fluids are more effective in reducing the cutting forces and increasing surface finish. It is also observed that the modified Pongamia oil showed lesser flank wear compared to the other two tested oils.
Pedestrian Motion Learning Based Indoor WLAN Localization via Spatial Clustering
Authors: Yang Xiaolong , Wang Yanmeng , Zhou Mu , Liu Yiyao
Published: May 2018

Applications on Location Based Services (LBSs) have driven the increasing demand for indoor localization technology. The conventional location fingerprinting based localization involves heavy time and labor cost for database construction, while the well‐known Simultaneous Localization and Mapping (SLAM) technique requires assistant motion sensors as well as complicated data fusion algorithms. To solve the above problems, a new pedestrian motion learning based indoor Wireless Local Area Network (WLAN) localization approach is proposed in this paper to achieve satisfactory LBS without the demand for location calibration or motion sensors. First of all, the concept of pedestrian motion learning is adopted to construct users’ motion paths in the target environment. Second, based on the timestamp relation of the collected Received Signal Strength (RSS) sequences, the RSS segments are constructed to obtain the signal clusters with the newly defined high‐dimensional linear distance. Third, the PageRank algorithm is performed to establish the hotspot mapping relations between the physical and signal spaces which are then used to localize the target. Finally, the experimental results show that the proposed approach can effectively estimate the target’s locations and analyze users’ motion preference in indoor environment.
Min‐Max‐MSE Transceiver Design for MU‐MIMO VLC System
Authors: Zeng Zhirong , Du Huiqin , Wu Zujian
Published: May 2018

This paper considers a multiuser (MU) multiple‐input multiple‐output (MIMO) visible light communication (VLC) system with broadcast channels. Due to the simultaneous transmission of the different source data to the receivers covered with the light rays, the interuser interference (IUI) may degrade the system performance. We strive to suppress the IUI by minimizing the maximum mean square errors (MSE) under the assumption of the perfect knowledge of channel state information (CSI). However, since the CSI may not be perfectly known in practice, a robust design is required against the channel uncertainties. Additionally, the nonnegativity and the limited linear range of the optical signals have been taken into account in the VLC transceiver designs. Simulation results validate that the proposed min‐max‐MSE approach can provide fair transmission, compared with the minimization of sum‐MSE approach. Furthermore, it is demonstrated that the robust scheme is capable of providing robustness and gaining a considerable bit error rate (BER) performance.
Complexity in Individual Trajectories toward Online Extremism
Authors: Cao Z. , Zheng M. , Vorobyeva Y. , Song C. , Johnson N. F.
Published: May 2018

Society faces a fundamental global problem of understanding which individuals are currently developing strong support for some extremist entity such as ISIS (Islamic State), even if they never end up doing anything in the real world. The importance of online connectivity in developing intent has been confirmed by recent case studies of already convicted terrorists. Here we use ideas from Complexity to identify dynamical patterns in the online trajectories that individuals take toward developing a high level of extremist support, specifically, for ISIS. Strong memory effects emerge among individuals whose transition is fastest and hence may become “out of the blue” threats in the real world. A generalization of diagrammatic expansion theory helps quantify these characteristics, including the impact of changes in geographical location, and can facilitate prediction of future risks. By quantifying the trajectories that individuals follow on their journey toward expressing high levels of pro‐ISIS support—irrespective of whether they then carry out a real‐world attack or not—our findings can help move safety debates beyond reliance on static watch‐list identifiers such as ethnic background or immigration status and/or postfact interviews with already convicted individuals. Given the broad commonality of social media platforms, our results likely apply quite generally; for example, even on Telegram where (like Twitter) there is no built‐in group feature as in our study, individuals tend to collectively build and pass through the so‐called super‐group accounts.
Controllability and Observability of Nonautonomous Riesz-Spectral Systems
Authors: Sutrima Sutrima , Indrati Christiana Rini , Aryati Lina
Published: May 2018

There are many industrial and biological reaction diffusion systems which involve the time-varying features where certain parameters of the system change during the process. A part of the transport-reaction phenomena is often modelled as an abstract nonautonomous equation generated by a (generalized) Riesz-spectral operator on a Hilbert space. The basic problems related to the equations are existence of solutions of the equations and how to control dynamical behaviour of the equations. In contrast to the autonomous control problems, theory of controllability and observability for the nonautonomous systems is less well established. In this paper, we consider some relevant aspects regarding the controllability and observability for the nonautonomous Riesz-spectral systems including the Sturm-Liouville systems using a C0-quasi-semigroup approach. Three examples are provided. The first is related to sufficient conditions for the existence of solutions and the others are to confirm the approximate controllability and observability of the nonautonomous Riesz-spectral systems and Sturm-Liouville systems, respectively.
Correlation Assisted Strong Uncorrelating Transform Complex Common Spatial Patterns for Spatially Distant Channel Data
Authors: Kim Youngjoo , You Jiwoo , Lee Heejun , Lee Seung Min , Park Cheolsoo
Published: May 2018

The Strong Uncorrelating Transform Complex Common Spatial Patterns (SUTCCSP) algorithm, designed for multichannel data analysis, has a limitation on keeping the correlation information among channels during the simultaneous diagonalization process of the covariance and pseudocovariance matrices. This paper focuses on the importance of preserving the correlation information among multichannel data and proposes the correlation assisted SUTCCSP (CASUT) algorithm to address this issue. The performance of the proposed algorithm was demonstrated by classifying the motor imagery electroencephalogram (EEG) dataset. The features were first extracted using CSP algorithms including the proposed method, and then the random forest classifier was utilized for the classification. Experiments using CASUT yielded an average classification accuracy of 78.10 (%), which significantly outperformed those of original CSP, Complex Common Spatial Patterns (CCSP), and SUTCCSP with p-values less than 0.01, tested by the Wilcoxon signed rank test.
Fluid Inclusions and C-H-O-S-Pb Isotope Systematics of the Changfagou Deposit, Jilin Province, Northeast China
Authors: Peng Bo , Li Bile , Chen Jun
Published: May 2018

The Changfagou Cu deposit in Jilin province, China, is located in the eastern segment of the northern margin of the North China Craton and lies at the southern end of the Lesser Xing’an Mountains-Zhanggangcailing Mountains. According to the mineral paragenetic association and its various relationships, the hydrothermal mineralization can be divided into 4 metallogenic stages from early to late: stage I is K-feldspar-quartz-magnetite, stage II is quartz-molybdenite, stage III is quartz-chalcopyrite (polymetallic sulfide), and stage IV is carbonate. Stages II and III are the main metallogenic stages. Overall, the metallogenic fluid associated with the Changfagou deposit is characterized as a F-rich CO2-H2O-NaCl hydrothermal system. The hydrogen and oxygen isotopic characteristics suggest the initial ore-forming fluids of the Changfagou deposit evolved from a primitive magmatic fluid and mixed with meteoric water. The sulfur and lead isotopic characteristics show that the metallogenic material was derived from partial melting of the lower crust. Phase separation or immiscibility is the important mechanism in the precipitation of molybdenum, whereas a decrease in temperature is the important mechanism in the precipitation of copper polymetallic sulfides. The above characteristics are similar to those of the porphyry deposits related to continental environments. Compared with the deposits in the Xilamulun metallogenic belt, both have similar metallogenic ages and tectonic positions. In conclusion, the Changfagou deposit formed in an intracontinental extensional environment due to lithospheric thinning. The mineralization was related to magmatism associated with partial melting of the lower crust. The intersection of the Dunhua-Mishan fracture and Kangbao-Chifeng fracture along the northern margin of the North China Craton is a promising location for porphyry ore deposits related to a continental tectonic setting.
Rainbow Gravity Corrections to the Entropic Force
Authors: Feng Zhong-Wen , Yang Shu-Zheng
Published: May 2018

The entropic force attracts a lot of interest for its multifunctional properties. For instance, Einstein’s field equation, Newton’s law of gravitation, and the Friedmann equation can be derived from the entropic force. In this paper, utilizing a new kind of rainbow gravity model that was proposed by Magueijo and Smolin, we explore the quantum gravity corrections to the entropic force. First, we derive the modified thermodynamics of a rainbow black hole via its surface gravity. Then, according to Verlinde’s theory, the quantum corrections to the entropic force are obtained. The result shows that the modified entropic force is related not only to the properties of the black hole but also to the Planck length lp and the rainbow parameter γ. Furthermore, based on the rainbow gravity corrected entropic force, the modified Einstein field equation and the modified Friedmann equation are also derived.
Optimization of Bioactive Ingredient Extraction from Chinese Herbal Medicine Glycyrrhiza glabra: A Comparative Study of Three Optimization Models
Authors: Yu Li , Jin Weifeng , Li Xiaohong , Zhang Yuyan
Published: May 2018

The ultraviolet spectrophotometric method is often used for determining the content of glycyrrhizic acid from Chinese herbal medicine Glycyrrhiza glabra. Based on the traditional single variable approach, four extraction parameters of ammonia concentration, ethanol concentration, circumfluence time, and liquid‐solid ratio are adopted as the independent extraction variables. In the present work, central composite design of four factors and five levels is applied to design the extraction experiments. Subsequently, the prediction models of response surface methodology, artificial neural networks, and genetic algorithm‐artificial neural networks are developed to analyze the obtained experimental data, while the genetic algorithm is utilized to find the optimal extraction parameters for the above well‐established models. It is found that the optimization of extraction technology is presented as ammonia concentration 0.595%, ethanol concentration 58.45%, return time 2.5 h, and liquid‐solid ratio 11.065 : 1. Under these conditions, the model predictive value is 381.24 mg, the experimental average value is 376.46 mg, and the expectation discrepancy is 4.78 mg. For the first time, a comparative study of these three approaches is conducted for the evaluation and optimization of the effects of the extraction independent variables. Furthermore, it is demonstrated that the combinational method of genetic algorithm and artificial neural networks provides a more reliable and more accurate strategy for design and optimization of glycyrrhizic acid extraction from Glycyrrhiza glabra.
Gleer: A Novel Gini‐Based Energy Balancing Scheme for Mobile Botnet Retopology
Authors: Wang Yichuan , Zhang Yefei , Ji Wenjiang , Zhu Lei , Liu Yanxiao
Published: May 2018

Mobile botnet has recently evolved due to the rapid growth of smartphone technologies. Unlike legacy botnets, mobile devices are characterized by limited power capacity, calculation capabilities, and wide communication methods. As such, the logical topology structure and communication mode have to be redesigned for mobile botnets to narrow energy gap and lower the reduction speed of nodes. In this paper, we try to design a novel Gini‐based energy balancing scheme (Gleer) for the atomic network, which is a fundamental component of the heterogeneous multilayer mobile botnet. Firstly, for each operation cycle, we utilize the dynamic energy threshold to categorize atomic network into two groups. Then, the Gini coefficient is introduced to estimate botnet energy gap and to regulate the probability for each node to be picked as a region C&C server. Experimental results indicate that our proposed method can effectively prolong the botnet lifetime and prevent the reduction of network size. Meanwhile, the stealthiness of botnet with Gleer scheme is analyzed from users’ perspective, and results show that the proposed scheme works well in the reduction of user’ detection awareness.
PHY‐Aided Secure Communication via Weighted Fractional Fourier Transform
Authors: Ni Lei , Da Xinyu , Hu Hang , Liang Yuan , Xu Ruiyang
Published: May 2018

A weighted fractional Fourier transform (WFRFT) based on channel state information (CSI), aiming to safeguard the physical (PHY) layer security of wireless communication system, is proposed. With the proposed scheme, WFRFT is first applied to satellite communications such that the transmitted signal is distorted and can only be neutralized by inverse‐WFRFT with the same parameter. Moreover, by exploiting the physical properties of wireless channels, the CSI matrix is transformed as a secret key. In addition, by adding phase rotation (PR) factors to each branch of the WFRFT system, a new unitary matrix with the encryption properties is constructed, and hence, the satellite communications secrecy is reliably guaranteed due to the variation in signal characteristics. Finally, the efficacy of the security enhancement is evaluated in terms of the average bit error rate (BER) and the secrecy capacity. Simulation results show that the proposed encryption method can make the detection and demodulation more difficult for the eavesdropper.
Atrial Fibrillation as a Rare Complication of the Use of Nifedipine as a Tocolytic Agent: A Case Report and Review of the Literature
Authors: Docheva Nikolina P. , Slutsky Emily D. , Sandelin Roger , Van Hook James W.
Published: May 2018

Calcium channel blockers are commonly used tocolytic agents on Labor and Delivery units worldwide as part of the management of preterm labor. Despite their overall reassuring safety profile, rare cardiovascular complications have been reported. In this report, we describe the case of threatened preterm labor managed with nifedipine with subsequent development of atrial fibrillation. This type of cardiac arrhythmia may have considerable consequences for both the mother and the fetus. The aim of this case report and comprehensive review of the literature is to raise awareness.
Sacubitril/Valsartanstive Heart Failure: Cardiogenic Shock
Authors: Rawal H. A. , Kocheril A. G.
Published: May 2018

Sacubitril/valsartan is a combination drug described as a new class of dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for heart failure. We present a case of a patient with NYHA class IV systolic heart failure who was refractory to all other classes of heart failure medications and was started on this new medication. On sacubitril/valsartan, he developed cardiogenic shock. This led us to reevaluate the use and risks of this medication in the class IV heart failure population.
Risk of Shiga Toxigenic Escherichia coli O157:H7 Infection from Raw and Fermented Milk in Sokoto Metropolis, Nigeria
Authors: Yakubu Yusuf , Shuaibu Abdulmalik Bello , Ibrahim Aliyu Musawa , Hassan Ummukulthum Lawal , Nwachukwu Raymond Junior
Published: May 2018

Escherichia coli O157:H7 is an enteric foodborne pathogen associated with life threatening disease conditions. The enterobacteria are frequently found in cattle gastrointestinal tract with high potential of contaminating animal products such as meat, milk, and cheese. A cross-sectional study was conducted to investigate the presence of Shiga toxin-producing Escherichia coli O157:H7 in milk products sold within Sokoto metropolis. Two hundred and sixty (260) samples (comprising 160 raw and 100 fermented milk samples) were collected from different sources within the study area. Bacteriological isolation and biochemical characterization yielded Escherichia coli with a detection rate of 9.23% (24/260). Molecular identification of the recovered isolates by PCR amplification of the Stx1 gene revealed Escherichia coli O157:H7 with a positive rate of 20.83% (5/24). The overall prevalence of E. coli O157:H7 was 1.92% (5/260) and the positive proportions for raw and fermented milk samples were 1.86% (3/160) and 2.0% (2/100), respectively. Fisher’s Exact test showed a nonsignificant association between the isolates and the different milk types (p=0.943; OR=0.94; [95% CI: 0.154–5.704]). The results revealed presence of Escherichia coli O157:H7 in raw and fermented milk sold within Sokoto metropolis, Nigeria. The findings indicate possible feacal contamination of the milk products, with serious public health consequences. This necessitates the need to screen other milk products produced in the area such as butter and cheese. Health authorities in the State need to enlighten dairy farmers on the zoonotic potential of Escherichia coli O157:H7 and the role of cattle in the spread of the pathogen.
Effective Approach to Calculate Analysis Window in Infinite Discrete Gabor Transform
Authors: Li Rui , Huang Yong , Liu Jia-Bao
Published: May 2018

The long‐periodic/infinite discrete Gabor transform (DGT) is more effective than the periodic/finite one in many applications. In this paper, a fast and effective approach is presented to efficiently compute the Gabor analysis window for arbitrary given synthesis window in DGT of long‐periodic/infinite sequences, in which the new orthogonality constraint between analysis window and synthesis window in DGT for long‐periodic/infinite sequences is derived and proved to be equivalent to the completeness condition of the long‐periodic/infinite DGT. By using the property of delta function, the original orthogonality can be expressed as a certain number of linear equation sets in both the critical sampling case and the oversampling case, which can be fast and efficiently calculated by fast discrete Fourier transform (FFT). The computational complexity of the proposed approach is analyzed and compared with that of the existing canonical algorithms. The numerical results indicate that the proposed approach is efficient and fast for computing Gabor analysis window in both the critical sampling case and the oversampling case in comparison to existing algorithms.
Characterization of Microscopic Pore Structures of Rock Salt through Mercury Injection and Nitrogen Absorption Tests
Authors: Chen Jianwen , Li Erbing , Luo Jin
Published: May 2018

Microscopic pore structure of rock salt plays a dominant role in its permeability. In this paper, microscopic pore structure of a set of rock salt samples collected from Yunying salt mine of Hubei province in China is investigated by high pressure mercury injection, rate-controlled mercury penetration, and nitrogen absorption tests. The pore size distribution is further evaluated based on fractal analysis. The results show that pore size of rock salt varies from 0.01 to 300 μm with major concentration of pore size smaller than 1.00 μm. The pore’s radiuses are mainly distributed within a range between 15 and 50 nm. The research further reveals that the pore channel size of rock salt is randomly distributed, but the distribution of pore throat radius fits very well with fractal law. By analysis of permeability, it is found that the maximum and medium radius of the pore throat have significant impacts on permeability. Porosity is not apparently related to the permeability of rock salt. The higher the fractal dimension is, the higher the impacts on permeability of the small throat are detected and the lower the influence on permeability of the big throat is exhibited. It indicates that the small throat determines majorly the permeability of rock salt. The findings obtained from this study provide an insight into understanding the characteristics of microscopic pore structure of rock salt.
Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer
Authors: Moses Michael A. , Kim Yeong Sang , Rivera-Marquez Genesis M. , Oshima Nobu , Watson Matthew J. , Beebe Kristin E. , Wells Catherine , Lee Sunmin , Zuehlke Abbey D. , Shao Hao , Bingman William E. , Kumar Vineet , Malhotra Sanjay V. , Weigel Nancy L. , Gestwicki Jason E. , Trepel Jane B. , Neckers Leonard M.
Published: May 2018

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling, in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small-molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with Hsp40. Pull-down studies using biotinylated-C86 found Hsp40 present in a multiprotein complex with full-length (FL-) AR, ARv7, and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric Hsp70 inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor, whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single-agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard antiandrogen therapy.

Significance:These findings highlight the feasibility of targeting the Hsp40/Hsp70 chaperone axis to treat CRPC that has become resistant to standard antiandrogen therapy. Cancer Res; 78(14); 4022–35. ©2018 AACR.
Preclinical Antitumor Activity of a Novel Anti–c-KIT Antibody–Drug Conjugate against Mutant and Wild-type c-KIT–Positive Solid Tumors
Authors: Abrams Tinya , Connor Anu , Fanton Christie , Cohen Steven B. , Huber Thomas , Miller Kathy , Hong E. Erica , Niu Xiaohong , Kline Janine , Ison-Dugenny Marjorie , Harris Sarah , Walker Dana , Krauser Klaus , Galimi Francesco , Wang Zhen , Ghoddusi Majid , Mansfield Keith , Lee-Hoeflich Si Tuen , Holash Jocelyn , Pryer Nancy , Kluwe William , Ettenberg Seth A. , Sellers William R. , Lees Emma , Kwon Paul , Abraham Judith A. , Schleyer Siew C.
Published: May 2018

Purpose: c-KIT overexpression is well recognized in cancers such as gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), melanoma, non–small cell lung cancer (NSCLC), and acute myelogenous leukemia (AML). Treatment with the small-molecule inhibitors imatinib, sunitinib, and regorafenib resulted in resistance (c-KIT mutant tumors) or limited activity (c-KIT wild-type tumors). We selected an anti–c-KIT ADC approach to evaluate the anticancer activity in multiple disease models.

Experimental Design: A humanized anti–c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a noncleavable linker (SMCC). The activity of the resulting ADC, LOP628, was evaluated in vitro against GIST, SCLC, and AML models and in vivo against GIST and SCLC models.

Results: LOP628 exhibited potent antiproliferative activity on c-KIT–positive cell lines, whereas LMJ729 displayed little to no effect. At exposures predicted to be clinically achievable, LOP628 demonstrated single administration regressions or stasis in GIST and SCLC xenograft models in mice. LOP628 also displayed superior efficacy in an imatinib-resistant GIST model. Further, LOP628 was well tolerated in monkeys with an adequate therapeutic index several fold above efficacious exposures. Safety findings were consistent with the pharmacodynamic effect of neutropenia due to c-KIT–directed targeting. Additional toxicities were considered off-target and were consistent with DM1, such as effects in the liver and hematopoietic/lymphatic system.

Conclusions: The preclinical findings suggest that the c-KIT–directed ADC may be a promising therapeutic for the treatment of mutant and wild-type c-KIT–positive cancers and supported the clinical evaluation of LOP628 in GIST, AML, and SCLC patients. Clin Cancer Res; 24(17); 4297–308. ©2018 AACR.
Abstract A03: Perturbation of proteostasis is lethal in SMARCB1-deficient tumors
Authors: Genovese Giannicola , Carugo Alessandro , Minelli Rosalba , Frederick  , Robinson Scott , Msaouel Pavlos , Heffernan Tim , Viale Andrea , Tannir Nizar , Draetta Giulio
Published: May 2018

Alterations in chromatin remodeling genes have been increasingly implicated in human oncogenesis. The SWI/SNF complex, specifically, is involved in a plethora of biologic functions including cell cycle regulation, terminal differentiation, and regulation of cell metabolism. The crucial chromatin-remodeling function of the SWI/SNF complex during organogenesis and tissue specification is further supported by clinical data showing that the biallelic inactivation of the core subunits SMARCB1 and SMARCA4 results in the emergence of extremely aggressive pediatric malignancies characterized by a dramatic impairment of cell cycle regulation and cellular differentiation programs, resulting in highly lethal diseases characterized by early onset, widespread metastatic dissemination, and resistance to chemotherapy. So far the lack of conditional genetic models of malignant rhabdoid tumors (MRTs) made difficult to investigate the molecular bases of malignant transformation as well as the existence of dependencies associated with SMARCB1 loss. In order to identify the functional vulnerabilities of SMARCB1-deficient cancers, we developed an embryonic mosaic model of malignant rhabdoid tumors (MRTs) that faithfully recapitulates the clinicopathologic features of human disease. By using this novel experimental system we discovered that, upon SMARCB1 ablation, embryonic epithelial progenitors undergo a profound anabolic reprogramming resulting in a global increase in protein biosynthesis and in the adaptive activation of UPR and ER stress response. As a consequence, murine and human SMARCB1-deficient malignancies display an exquisite sensitivity to agents inducing proteotoxic stress and to the pharmacologic and genetic perturbation of autophagy. Our findings, therefore, have immediate clinical implications, paving the way for drug repositioning trials investigating combinations of agents with already known safety profiles targeting simultaneously UPR and the authopagic catabolic machinery in a class of orphan diseases affecting children with limited therapeutic options.

Note: This abstract was not presented at the conference.

Citation Format: Giannicola Genovese, Alessandro Carugo, Rosalba Minelli, Frederick, Scott Robinson, Pavlos Msaouel, Tim Heffernan, Andrea Viale, Nizar Tannir, Giulio Draetta. Perturbation of proteostasis is lethal in SMARCB1-deficient tumors [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A03.
Abstract A05: Investigating mechanisms of obesity-mediated pancreatic cancer progression
Authors: Muzumdar Mandar Deepak , Dorans Kimberly Judith , Chung Katherine Minjee , Bhutkar Arjun , Fuchs Charles , Jacks Tyler
Published: May 2018

Genetically engineered mouse models (GEMMs) that faithfully recapitulate the genetics and histology of human tumors are an underutilized tool to understand how modifiable risk factors influence tumor development. Prospective cohort studies have shown that obesity is associated with an increased risk of developing pancreatic cancer, more advanced disease at diagnosis, and worse survival, though the precise mechanisms behind which obesity contributes to cancer progression remain elusive. We crossed mice harboring loss-of-function mutations in the leptin gene (ob/ob) with Pdx1-Cre; LSL-KrasG12D (KC) mice predisposed to initiate pancreatic cancers. KC; ob/ob mice are obese and exhibit markedly shortened survival (~4 months vs. ~1 year), increased primary tumor burden, and enhanced progression to adenocarcinoma compared to nonobese KC mice. Interestingly, early correction of leptin deficiency using an adeno-associated virus (AAV)-based approach induces rapid normalization of body weight and hyperglycemia and completely prevents the emergence of enhanced tumor burden. In contrast, late leptin restoration following tumor progression does not impact survival. These data suggest a causal and reversible role for obesity in early pancreatic cancer progression. Furthermore, by evaluating the degree by which alternative interventions phenocopy the effects of leptin restoration, we have developed a model to rapidly interrogate mechanisms of obesity-mediated tumor progression. As a proof of principle, we have tested the ability of immunomodulatory (aspirin) and antidiabetic (metformin) agents, observed to impact pancreatic cancer risk and survival in human cohorts, to intercept cancer progression in this model. Finally, combined molecular and biochemical analyses of tumors reveal increased immune cell activation and fibrosis in KC; ob/ob mice compared to nonobese KC and KC; p53 mutant mice and provide specific molecular targets to evaluate for pancreatic cancer therapy and prevention.

Citation Format: Mandar Deepak Muzumdar, Kimberly Judith Dorans, Katherine Minjee Chung, Arjun Bhutkar, Charles Fuchs, Tyler Jacks. Investigating mechanisms of obesity-mediated pancreatic cancer progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A05.
Abstract A18: Generation of new conditional Kras-alleles by CRISPR-based genome editing
Authors: Zafra Maria Paz , Schatoff Emma M. , Han Teng , Dow Lukas E.
Published: May 2018

KRAS is the most frequently mutated oncogene in human cancers, and specific cancer types show a clear bias in the types and frequency of Kras alterations. However, we do not have a clear understanding of how distinct Kras mutations dictate tumor biology and response to therapy. The generation of conditional animal models, such as Lox-Stop-Lox (LSL) KrasG12D and LSL-KrasG12Vgeo mice, has provided important tools to dissect the impact of Kras mutation in tumor development, but these models alone do not recapitulate the spectrum of Kras alterations in human cancer. To better reflect the Kras mutational landscape in human cancers, we have developed a series of critical LSL-Kras mouse models that recapitulate common Kras alterations observed in colorectal (G13D), pancreatic (G12R), and lung cancer (G12C), allowing the direct interrogation of the effects of these Kras mutations on disease phenotype and treatment response.

To do this, we targeted embryonic stem cells (ESCs) carrying the LSL-KrasG12D allele, by co-transfection of a modified high-fidelity Cas9 (Cas9-HFz), a LSL-Kras-targeted sgRNA, and an HDR template carrying the new mutation. While Cas9-HFz displayed a slight decrease in homology-directed repair (HDR) efficiency in comparison with wild-type Cas9, it enabled high specificity editing of only the LSL allele. Targeted deep sequencing revealed a significant reduction in “off-target” events in wild-type Kras locus in Cas9-HFz transfected samples compared to unmodified Cas9. We next generated transgenic mice by blastocyst injection and produced mice carrying each LSL-Kras variant, a pancreas-specific Cre (p48-Cre), and a far-red fluorescent Cre-reporter (mKate2). We are now analyzing the impact of specific Kras alterations in tumor initiation in distinct tissues such as the pancreas, colon, and lung. Together with available LSL-KrasG12D and LSL-KrasG12V already available, our new alleles will serve as critical tools for better dissecting the genetic factors that dictate disease initiation, progression, and response to therapy.

Citation Format: Maria Paz Zafra, Emma M. Schatoff, Teng Han, Lukas E. Dow. Generation of new conditional Kras-alleles by CRISPR-based genome editing [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A18.