bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperspectral Image Classification Using Spatial and Edge Features Based on Deep Learning
Authors: Zhang Dexiang , Kang Jingzhong , Xun Lina , Huang Yu
Published: December 2018

In recent years, deep learning has been widely used in the classification of hyperspectral images and good results have been achieved. But it is easy to ignore the edge information of the image when using the spatial features of hyperspectral images to carry out the classification experiments. In order to make full use of the advantages of convolution neural network (CNN), we extract the spatial information with the method of minimum noise fraction (MNF) and the edge information by bilateral filter. The combination of the two kinds of information not only increases the useful information but also effectively removes part of the noise. The convolution neural network is used to extract features and classify for hyperspectral images on the basis of this fused information. In addition, this paper also uses another kind of edge-filtering method to amend the final classification results for a better accuracy. The proposed method was tested on three public available data sets: the University of Pavia, the Salinas, and the Indian Pines. The competitive results indicate that our approach can realize a classification of different ground targets with a very high accuracy.
Design of Dual-Sampling and Adaptive Predictive PID Controller for Buck DC–DC Converters
Authors: Chang Changyuan , Liu Jidong
Published: December 2018

In this paper, based on the combination scheme of dual-sampling and adaptive predictive PID control, a digital controller for improving the transient performance of Buck DC–DC converters is designed. Due to the inherent loop delay in analog-to-digital (A/D) conversion, the calculation process of the digital controller and digital pulse width modulator (DPWM) of conventional digitally-controlled Buck DC–DC converters limits the system bandwidth and this makes the transient response lower. The designed digital controller can reduce the delay time in analog-to-digital converter (ADC), the digital controller and DPWM of digitally-controlled Buck DC–DC converters. Adaptive predictive control is used to eliminate the delay time of ADC and the digital controller, while dual-sampling scheme is used to reduce the delay time of DPWM in this paper. These are two new control schemes, and they show better performance in improving the transient response than other existing control schemes. Both simulation and experimental results demonstrate that the designed digital controller based on dual-sampling and adaptive predictive PID control is effective in improving the transient performance of Buck DC–DC converters. During experimental verification, for a load step between 0.5[Formula: see text]A and 1.0[Formula: see text]A, the fastest transient recovery time and the overshoot voltage are found to be 102[Formula: see text][Formula: see text]s and 120[Formula: see text]mV, respectively. Compared with the conventional digital PID controller, the transient recovery time and the overshoot voltage of the digital controller designed in this paper are decreased by 40.0% and 27.3%, respectively.
A New Floating Memristor Based on CBTA with Grounded Capacitors
Authors: Yesil Abdullah , Babacan Yunus , Kacar Fırat
Published: December 2018

This paper presents a new floating memristor emulator (FME) consisting of only a single current backward transconductance amplifier (CBTA) as the active element and two grounded capacitors. The proposed FME-based on CBTA enjoys some advantages that include minimum active and passive elements without using an analog multiplier circuit and grounded passive elements which are attractive for the integrated circuit. In addition, excluding the DC power supply voltage, it does not use bias voltage and/or bias current. The designed memristor circuit provides incremental and decremental characteristics without changing circuit topology or using a switching mechanism and it is implemented with a minimum of circuit elements. All simulation results for the memristor emulator were obtained as expected when compared with fabricated memristors.
Exponential boundary feedback stabilization of a shock steady state for the inviscid Burgers equation
Authors: Bastin Georges , Coron Jean-Michel , Hayat Amaury , Shang Peipei
Published: December 2018

In this paper, we study the exponential stabilization of a shock steady state for the inviscid Burgers equation on a bounded interval. Our analysis relies on the construction of an explicit strict control Lyapunov function. We prove that by appropriately choosing the feedback boundary conditions, we can stabilize the state as well as the shock location to the desired steady state in [Formula: see text]-norm, with an arbitrary decay rate.
The semi-martingale equilibrium equity premium for risk-neutral investors
Authors: Mukupa George M. , Offen Elias R.
Published: December 2018

In this paper, we study the risk-neutral investor’s equilibrium equity premium in a semi-martingale market with arbitrary, normal, binomial and gamma jumps. We simulate graphs for discrete distribution of jump amplitudes in order to study the parameter effect. The equity premium for this investor remains the same regardless of [Formula: see text] and [Formula: see text] variations in the linear utility function. In fact, there is no optimal consumption for [Formula: see text]. For normal jumps, our results are consistent with the risk-averse investor’s power utility effect on the equity premium. However, the binomial and gamma amplitudes show significant variations between risk neutrality and risk aversion.
FIRST
Authors: Restuccia Francesco , Ferraro Pierluca , Sanders Timothy S. , Silvestri Simone , Das Sajal K. , Re Giuseppe Lo
Published: December 2018

Thanks to the collective action of participating smartphone users, mobile crowdsensing allows data collection at a scale and pace that was once impossible. The biggest challenge to overcome in mobile crowdsensing is that participants may exhibit malicious or unreliable behavior, thus compromising the accuracy of the data collection process. Therefore, it becomes imperative to design algorithms to accurately classify between reliable and unreliable sensing reports. To address this crucial issue, we propose a novel Framework for optimizing Information Reliability in Smartphone-based participaTory sensing (FIRST) that leverages mobile trusted participants (MTPs) to securely assess the reliability of sensing reports. FIRST models and solves the challenging problem of determining before deployment the minimum number of MTPs to be used to achieve desired classification accuracy. After a rigorous mathematical study of its performance, we extensively evaluate FIRST through an implementation in iOS and Android of a room occupancy monitoring system and through simulations with real-world mobility traces. Experimental results demonstrate that FIRST reduces significantly the impact of three security attacks (i.e., corruption, on/off, and collusion) by achieving a classification accuracy of almost 80% in the considered scenarios. Finally, we discuss our ongoing research efforts to test the performance of FIRST as part of the National Map Corps project.
A Framework for the Inference of Sensing Measurements Based on Correlation
Authors: Silvestri Simone , Urgaonkar Rahul , Zafer Murtaza , Ko Bong Jun
Published: December 2018

Sensor networks are commonly adopted to collect a variety of measurements in indoor and outdoor settings. However, collecting such measurements from every node in the network, although providing high accuracy and resolution of the phenomena of interest, may easily cause sensors’ battery depletion. In this article, we show that measurement correlation can be successfully exploited to reduce the amount of data collected in the network without significantly sacrificing the monitoring accuracy. In particular, we propose an online adaptive measurement technique with which a subset of nodes are dynamically chosen as
monitors
while the measurements of the remaining nodes are estimated using the computed correlations. We propose an estimation framework based on jointly Gaussian distributed random variables, and we formulate an optimization problem to select the monitors under a total cost constraint. We show that the problem is NP-Hard and propose three efficient heuristics. We also develop statistical approaches that automatically switch between learning and estimation phases to take into account the variability occurring in real networks. Simulations carried out on real-world traces show that our approach outperforms previous solutions based on compressed sensing, and it can be successfully applied to the real application of solar irradiance prediction of photovoltaics systems.
Review of Modern Data Science
Authors: Miller Allan M.
Published: December 2018

Modern Data Science with R (MDSR) is one of the first textbooks to provide a comprehensive introduction to data science for students at the undergraduate level (it is also suitable for graduate students and professionals in other fields). The authors follow the approach taken by Garrett Grolemund and Hadley Wickham in their book, R for Data Science7, and David Robinson in Teach the Tidyverse to Beginners, which emphasizes the teaching of data visualization and the tidyverse (using dplyr and chained pipes) before covering base R, along with using real-world data and modern data science methods.

The textbook includes end of chapter exercises (an instructor's solution manual is available), and a series of lab activities is also under development. The result is an excellent textbook that provides a solid foundation in data science for students and professionals alike.
Edsger W. Dijkstra
Authors: Alpern Bowen
Published: December 2018

It would be understatement to say that news of this year's Dijkstra award came to me as a surprise. In fact, it put me into a rather profound funk, occasioning unsought re ection on my arguably misspent adulthood. It has been some time since I have done signi cant scienti c research. So, I am quite humbled to be here.

I did not really know Dijkstra, but I certainly knew of him. With Fred and David Gries on the faculty, his in uence on the Computer Science Department at Cornell was substantial when I was a graduate student. (I trust it still is.)
Dual Equivalent Lateral Force Method for Low‐Rise Wooden Horizontal Hybrid Structure with Rigid Core
Authors: Wu Di , Yamazaki Yoshihiro , Sakata Hiroyasu
Published: December 2018

Hybrid structure has shown some great features in the earthquake‐resistant design. However, due to the different properties between the combined building systems, the distributions of structural mass and stiffness are prevalently irregular in breadth or height, which makes the widely used equivalent lateral force (ELF) method powerless to predict the seismic shear force of such hybrid structure. This study proposed a simple design procedure for determining the concerned seismic shear force of low‐rise wooden horizontal hybrid structure in the preliminary linear design. The dual equivalent lateral force (DELF) method is presented that permits the extension of the ELF method by separating the hybrid structure into two independent substructures. It is shown that the proposed DELF method is sufficient to provide a reasonable estimation of the seismic shear force with satisfied accuracy.
A Step towards Integrating CMORPH Precipitation Estimation with Rain Gauge Measurements
Authors: Pereira Filho Augusto José , Vemado Felipe , Vemado Guilherme , Gomes Vieira Reis Fábio Augusto , Giordano Lucilia do Carmo , Cerri Rodrigo Irineu , Santos Cláudia Cristina dos , Sampaio Lopes Eymar Silva , Gramani Marcelo Fischer , Ogura Agostinho Tadashi , Zaine José Eduardo , Cerri Leandro Eugenio da Silva , Augusto Filho Oswaldo , D’Affonseca Fernando Mazo , Amaral Cláudio dos Santos
Published: December 2018

Accurate daily rainfall estimation is required in several applications such as in hydrology, hydrometeorology, water resources management, geomorphology, civil protection, and agriculture, among others. CMORPH daily rainfall estimations were integrated with rain gauge measurements in Brazil between 2000 and 2015, in order to reduce daily rainfall estimation errors by means of the statistical objective analysis scheme (SOAS). Early comparisons indicated high discrepancies between daily rain gauge rainfall measurements and respective CMORPH areal rainfall accumulation estimates that tended to be reduced with accumulation time span (e.g., yearly accumulation). Current results show CMORPH systematically underestimates daily rainfall accumulation along the coastal areas. The normalized error variance (NEXERVA) is higher in sparsely gauged areas at Brazilian North and Central-West regions. Monthly areal rainfall averages and standard deviation were obtained for eleven Brazilian watersheds. While an overall negative tendency (3 mm·h−1) was estimated, the Amazon watershed presented a long-term positive tendency. Monthly areal mean precipitation and respective spatial standard deviation closely follow a power-law relationship for data-rich watersheds, i.e., with denser rain gauge networks. Daily SOAS rainfall accumulation was also used to calculate the spatial distribution of frequencies of 3-day rainfall episodes greater than 100 mm. Frequencies greater than 3% were identified downwind of the Peruvian Andes, the Bolivian Amazon Basin, and the La Plata Basin, as well as along the Brazilian coast, where landslides are recurrently triggered by precipitation.
Formation‐Containment Control of Second‐Order Multiagent Systems via Intermittent Communication
Authors: Xia Mao-Dong , Liu Cheng-Lin , Liu Fei
Published: December 2018

This paper investigates the formation‐containment control of second‐order multiagent systems with intermittent communication. Distributed coordination control algorithms are proposed under aperiodic intermittent communication, where each agent only communicates with its neighboring agents on some disconnected time intervals. By means of constructing Lyapunov functions, sufficient convergence conditions are obtained for the leaders reaching a prescribed formation asymptotically and the followers converging into the convex hull formed by leaders asymptotically, respectively. Besides, sufficient convergence conditions are also provided for second‐order multiagent systems converging to the desired formation‐containment under time‐varying communication delay and intermittent communication. Finally, the validity of theoretical results is illustrated by numerical simulations.
Systematic Understanding of the Mechanism of Baicalin against Ischemic Stroke through a Network Pharmacology Approach
Authors: Xu Tian , Ma Chongyang , Fan Shuning , Deng Nang , Lian Yajun , Tan Ling , Du Weizhe , Zhang Shuang , Liu Shuling , Ren Beida , Li Zhenhan , Wang Qinguo , Wang Xueqian , Cheng Fafeng
Published: December 2018

Ischemic stroke is accompanied by high mortality and morbidity rates. At present, there is no effective clinical treatment. Alternatively, traditional Chinese medicine has been widely used in China and Japan for the treatment of ischemic stroke. Baicalin is a flavonoid extracted from Scutellaria baicalensis that has been shown to be effective against ischemic stroke; however, its mechanism has not been fully elucidated. Based on network pharmacology, we explored the potential mechanism of baicalin on a system level. After obtaining baicalin structural information from the PubChem database, an approach combined with literature mining and PharmMapper prediction was used to uncover baicalin targets. Ischemic stroke‐related targets were gathered with the help of DrugBank, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). Protein‐protein interaction (PPI) networks were constructed through the Cytoscape plugin BisoGenet and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. We obtained a total of 386 potential targets and 5 signaling pathways, including mitogen‐activated protein kinase (MAPK), phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT), hypoxia‐inducible factor‐1 (HIF‐1), nuclear factor kappa B (NF‐κB), and forkhead box (FOXO) signaling pathways. GO analysis showed that these targets were associated with antiapoptosis, antioxidative stress, anti‐inflammation, and other physiopathological processes that are involved in anti‐ischemic stroke effects. In summary, the mechanism of baicalin against ischemic stroke involved multiple targets and signaling pathways. Our study provides a network pharmacology framework for future research on traditional Chinese medicine.
Agent-Based Simulation and Its Application to Analyze Combat Effectiveness in Network-Centric Warfare Considering Communication Failure Environments
Authors: Lee Jaeyeong , Shin Sunwoo , Park Moonsung , Kim Chongman
Published: December 2018

Many parts of platforms are expected to be replaced by unmanned systems in modern warfare. All the assets and supporting vehicles are linked to each other with a communication network, and it is called the network-centric warfare environment. Hence, it is critical when communication failure occurs during engagement in ground battlefield because this failure will directly affect overall combat effectiveness of one’s owned assets. However, research regarding communication failure issues is scarce. We herein propose a new agent-based modeling process to measure the overall combat effectiveness combined with communication success ratio, based on the terrain condition of the ground engagement. Additionally, we provide the effectiveness analysis result when a communication repeater is applied during communication failure as an alternative measure.
Cardiac Sarcoidosis as an Uncommon Etiology for Posterior Circulation Stroke Presenting with Alexia without Agraphia
Authors: Kurukumbi Mohankumar , Gardiner Lauren , Sahai Shevani , Cochran John W.
Published: December 2018

Sarcoidosis is a systemic disease with cardiac involvement occurring in 20-50% of cases. Cardiogenic stroke caused by cardiac sarcoidosis, especially PCA infarction, is a rare clinical presentation that necessitates timely diagnosis and may warrant treatment prophylaxis against CVA. In this case report, we describe a 54-year-old Caucasian male presenting with left PCA stroke in the setting of cardiac and pulmonary sarcoidosis, and hypertension. His presenting symptoms included right partial hemianopia, difficulty with naming, memory, and recall, and alexia without agraphia. Cardiogenic stroke is an uncommon manifestation of cardiac sarcoidosis, and given the disabling nature of these sequelae, the importance of early diagnosis and prevention with anticoagulation is crucial to prevent morbidity and mortality.
Primary Epithelioid Sarcoma of Orbit: A Case Report and Review of the Literature
Authors: Kaya Erin A. , Broadbent Talmage J. , Thomas Cheddhi J. , Wagner Aaron E. , Thatcher Steve H. , Lamoreaux Wayne T. , Fairbanks Robert K. , Lee Christopher M.
Published: December 2018

Epithelioid sarcoma is a rare high-grade malignancy identified by Enzinger in 1970. It accounts for 1% of all reported soft tissue sarcomas and presents most commonly in distal upper extremities in young adults with a male predominance. At this time, there are only 5 previously reported cases of primary epithelioid sarcoma of the orbit. We present a primary orbital epithelioid sarcoma case of a patient who underwent orbital exenteration followed by external beam radiation treatment. Because the literature is limited, this is to our knowledge the largest descriptive analysis of cases of orbital epithelioid sarcoma. We also provide a detailed review of all the previously reported primary orbital epithelioid sarcoma cases, as well as a discussion on the use of postoperative radiation therapy for patients with epithelioid sarcoma. Surgical resection followed by adjuvant radiation therapy appears to be a safe option for local treatment of this rare malignancy, but further future studies are needed of this rare clinical situation in order to better understand and optimize treatment for patients with orbital epithelioid sarcoma.
Isoproterenol Induced Insulin Resistance Leading to Diabetic Ketoacidosis in Type 1 Diabetes Mellitus
Authors: Hoff Ryan , Koh Chung-Kay
Published: December 2018

Isoproterenol is known to cause insulin resistance and is often used to treat bradyarrhythmias from atrioventricular block. We report a case of isoproterenol induced diabetic ketoacidosis in a 77-year-old female patient treated with isoproterenol for atrioventricular block prior to insertion of permanent pacemaker. Diabetic ketoacidosis (DKA) developed within hours of starting an isoproterenol drip, and there were no other precipitating factors at that time. DKA resolved quickly after discontinuing isoproterenol and starting insulin drip. DKA is a common complication of diabetes mellitus, with about 140,000 hospital admissions for DKA in 2009. While the rate of DKA has increased by nearly 50% between 1988 and 2009, the rate of mortality has decreased. There are many causes of diabetic ketoacidosis, such as medication noncompliance, infection, pancreatitis, stroke, myocardial infarction, and many others. Isoproterenol may lead to diabetic ketoacidosis by increasing insulin resistance.
Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6brd10 Mouse Model of Retinitis Pigmentosa
Authors: Yu Minzhong , Yan Weiming , Beight Craig
Published: December 2018

Purpose. Lutein, RR-zeaxanthin, and RS-zeaxanthin (L-Z) are antioxidants which can reduce endoplasmic reticulum stress (ERS) and oxidative stress (OS), and ameliorate neurodegenerative diseases. However, their treatment effect in the Pde6brd10 (rd10) mouse model of retinitis pigmentosa (RP) and the underlying cellular mechanisms have not been studied. ERS is an important factor which causes photoreceptor apoptosis. The aim of the current project is to test the treatment effect of L-Z in rd10 mice and to investigate the underlying molecular mechanisms of ERS. Methods. L-Z (Lutemax 2020, 10 mg/kg) diluted in sunflower oil (SFO, 1 mg/ml) or the same volume of SFO was administrated via gavage from postnatal day 6 (P6) to P20 daily in L-Z group (n=5) or SFO group (n=6) of rd10 mice. At P21, electroretinography (ERG) was performed to show the functional change of retinas. 78 kDa glucose-regulated protein (GRP78) and endoplasmic reticulum protein 29 (ERp29) were tested by western blot and immunostaining. Results. The ERG amplitudes were larger in the L-Z group than those of the SFO group in all flash luminances of dark-adapted and light-adapted ERG (all p < 0.01). Western blot revealed that GRP78 in the retinas of the L-Z group was significantly downregulated compared to that of the SFO group (p < 0.01). Meanwhile, the retinal ERp29 protein was significantly upregulated in the L-Z treatment group than that of the SFO group (p < 0.01). Conclusions. L-Z provide protection to the photoreceptors of rd10 mouse model of RP, which is probably associated with the reduction of ERS.
Combination of Epigallocatechin Gallate and Sulforaphane Counteracts In Vitro Oxidative Stress and Delays Stemness Loss of Amniotic Fluid Stem Cells
Authors: Marrazzo Pasquale , Angeloni Cristina , Freschi Michela , Lorenzini Antonello , Prata Cecilia , Maraldi Tullia , Hrelia Silvana
Published: December 2018

Amniotic fluid stem cells (AFSCs) are characterized in vivo by a unique niche guarantying their homeostatic role in the body. Maintaining the functionality of stem cells ex vivo for clinical applications requires a continuous improvement of cell culture conditions. Cellular redox status plays an important role in stem cell biology as long as reactive oxygen species (ROS) concentration is finely regulated and their adverse effects are excluded. The aim of this study was to investigate the protective effect of two antioxidants, sulforaphane (SF) and epigallocatechin gallate (EGCG), against in vitro oxidative stress due to hyperoxia and freeze‐thawing cycles in AFSCs. Human AFSCs were isolated and characterized from healthy subjects. Assays of metabolic function and antioxidant activity were performed to investigate the effect of SF and EGCG cotreatment on AFSCs. Real‐time PCR was used to investigate the effect of the cotreatment on pluripotency, senescence, osteogenic and adipogenic markers, and antioxidant enzymes. Alkaline phosphatase assays and Alizarin Red staining were used to confirm osteogenic differentiation. The cotreatment with SF and EGCG was effective in reducing ROS production, increasing GSH levels, and enhancing the endogenous antioxidant defences through the upregulation of glutathione reductase, NAD(P)H:quinone oxidoreductase‐1, and thioredoxin reductase. Intriguingly, the cotreatment sustained the stemness state by upregulating pluripotency markers such as OCT4 and NANOG. Moreover, the cotreatment influenced senescence‐associated gene markers in respect to untreated cells. The cotreatment upregulated osteogenic gene markers and promoted osteogenic differentiation in vitro. SF and EGCG can be used in combination in AFSC culture as a strategy to preserve stem cell functionality.
An Improved Kernelized Correlation Filter Based Visual Tracking Method
Authors: Ni Jianjun , Zhang Xue , Shi Pengfei , Zhu Jinxiu
Published: December 2018

Correlation filter based trackers have received great attention in the field of visual target tracking, which have shown impressive advantages in terms of accuracy, robustness, and speed. However, there are still some challenges that exist in the correlation filter based methods, such as target scale variation and occlusion. To deal with these problems, an improved kernelized correlation filter (KCF) tracker is proposed, by employing the GM(1,1) grey model, the interval template matching method, and multiblock scheme. In addition, a strict template update strategy is presented in the proposed method to accommodate the appearance change and avoid template corruption. Finally, some experiments are conducted. The proposed method is compared with the top state-of-the-art trackers, and all the tracking algorithms are evaluated on the object tracking benchmark. The experimental results demonstrate obvious improvements of the proposed KCF-based visual tracking method.
Bound State of Heavy Quarks Using a General Polynomial Potential
Authors: Mansour Hesham , Gamal Ahmed
Published: December 2018

In the present work, the mass spectra of the bound states of heavy quarkscc-,bb-, andBcmeson are studied within the framework of the nonrelativistic Schrödinger’s equation. First, we solve Schrödinger’s equation with a general polynomial potential by Nikiforov-Uvarov (NU) method. The energy eigenvalues for any L- value is presented for a special case of the potential. The results obtained are in good agreement with the experimental data and are better than previous theoretical studies.
A New Insight into the Roles of MiRNAs in Metabolic Syndrome
Authors: Huang Yuxiang , Yan Yuxiang , Xv Weicheng , Qian Ge , Li Chijian , Zou Hequn , Li Yongqiang
Published: December 2018

Metabolic syndrome (MetS), which includes several clinical components such as abdominal obesity, insulin resistance (IR), dyslipidemia, microalbuminuria, hypertension, proinflammatory state, and oxidative stress (OS), has become a global epidemic health issue contributing to a high risk of type 2 diabetes mellitus (T2DM). In recent years, microRNAs (miRNAs), used as noninvasive biomarkers for diagnosis and therapy, have aroused global interest in complex processes in health and diseases, including MetS and its components. MiRNAs can exist stably in serum, liver, skeletal muscle (SM), heart muscle, adipose tissue (AT), andβcells, because of their ability to escape the digestion of RNase. Here we first present an overall review on recent findings of the relationship between miRNAs and several main components of MetS, such as IR, obesity, diabetes, lipid metabolism, hypertension, hyperuricemia, and stress, to illustrate the targeting proteins or relevant pathways that are involved in the progress of MetS and also help us find promising novel diagnostic and therapeutic strategies.
Loss of BRCA1 Spontaneously Induces the Tumorigenesis in Lacrimal Gland
Authors: Kim Sun Eui , Baek Hye Jung , Park Eun Jung , Lim Sung Chul , Kim Sang Soo
Published: December 2018

Environmental and genetic factors exert important influences on lifespan and neoplastic transformation. We have previously shown that spontaneous tumors form frequently in mice homozygous for a full-length Brca1 deletion. In general, mutations of BRCA1 are closely associated with induction of breast and ovarian cancers but are also known to contribute to the incidence of other cancers at a low frequency. Female Brca1-mutant mice (Brca1co/coMMTV-cre) were generated by crossing Brca1 conditional knockout mice and MMTV-cre mice, and the occurrence of lacrimal gland abnormalities and tumors was followed until mice reached 18 months of age. Lacrimal gland tumors, which occur at a very low frequency in the human population (1 per 1,000,000 per year), were detected in 7 cases of Brca1co/coMMTV-cre mice (2.75%) older than 9 months of age. None of seven mice exhibited any abnormality in the mammary gland including neoplasia, suggesting lacrimal gland tumor is spontaneously and independently formed. These tumors, which were detected in seven mutant mice that displayed exophthalmoses, were malignant, originated from epithelial cells, and were identified as acinic cell carcinoma by pathological analysis. Further analysis revealed that tumorigenesis was accompanied by the accumulation of cyclin D1 and decreased expression of the cellular oncogenes, c-Myc, c-Jun, and c-Raf. Tumors also exhibited rearrangement of cytoskeletal proteins, including β-catenin, keratin 5, and vimentin, depending on tumor progression. These results suggest that BRCA1 is involved in genetic stability of the lacrimal gland, providing new insight into genomic instability in organism maintenance and tumorigenesis of the lacrimal gland.
Rare Anomaly of Common Bile Duct in Association with Distal Cholangiocarcinoma
Authors: Pandey Arun , Mandal Rajesh , Lakhey Paleswan Joshi
Published: December 2018

Duplication of common bile duct is a rare entity and its association with distal cholangiocarcinoma is extremely rare. It represents failure of regression of the embryological double biliary system. Here, we describe the diagnostic and therapeutic challenges of a type I variant of the extrahepatic bile duct duplication coexistent with distal cholangiocarcinoma that was diagnosed intraoperatively while treating with Whipple procedure for distal cholangiocarcinoma.
Different Forms of ER Stress in Chondrocytes Result in Short Stature Disorders and Degenerative Cartilage Diseases: New Insights by Cartilage‐Specific ERp57 Knockout Mice
Authors: Rellmann Yvonne , Dreier Rita
Published: December 2018

Cartilage is essential for skeletal development by endochondral ossification. The only cell type within the tissue, the chondrocyte, is responsible for the production of macromolecules for the extracellular matrix (ECM). Before proteins and proteoglycans are secreted, they undergo posttranslational modification and folding in the endoplasmic reticulum (ER). However, the ER folding capacity in the chondrocytes has to be balanced with physiological parameters like energy and oxygen levels. Specific cellular conditions, e.g., a high protein demand, or pathologic situations disrupt ER homeostasis and lead to the accumulation of poorly folded or misfolded proteins. This state is called ER stress and induces a cellular quality control system, the unfolded protein response (UPR), to restore homeostasis. Different mouse models with ER stress in chondrocytes display comparable skeletal phenotypes representing chondrodysplasias. Therefore, ER stress itself seems to be involved in the pathogenesis of these diseases. It is remarkable that chondrodysplasias with a comparable phenotype arise independent from the sources of ER stress, which are as follows: (1) mutations in ECM proteins leading to aggregation, (2) deficiencies in ER chaperones, (3) mutations in UPR signaling factors, or (4) deficiencies in the degradation of aggregated proteins. In any case, the resulting UPR substantially impairs ECM protein synthesis, chondrocyte proliferation, and/or differentiation or regulation of autophagy and apoptosis. Notably, chondrodysplasias arise no matter if single or multiple events are affected. We analyzed cartilage‐specific ERp57 knockout mice and demonstrated that the deficiency of this single protein disulfide isomerase, which is responsible for formation of disulfide bridges in ECM glycoproteins, is sufficient to induce ER stress and to cause an ER stress‐related bone phenotype. These mice therefore qualify as a novel model for the analysis of ER stress in chondrocytes. They give new insights in ER stress‐related short stature disorders and enable the analysis of ER stress in other cartilage diseases, such as osteoarthritis.
Effect of Aidi Injection plus TACE on Hepatocellular Carcinoma: A Meta‐Analysis of Randomized Controlled Trials
Authors: Dai Yaoyao , Gao Sicheng , Liu Xing , Gao Qin , Zhang Lan , Fan Xingliang , Zhu Junfeng
Published: December 2018

We aim to conduct a meta‐analysis of studies on the effect of Aidi injection combined with TACE in the treatment of hepatocellular carcinoma (HCC). China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Allied and Complementary Medicine Database (AMED), EMBASE, Web of Science, PubMed, and Cochrane Library databases to October 1, 2017, were searched to collect the studies. The data analysis was performed using RevMan 5.3 software. Totally 20 clinical trials with 774 (the experimental group: 447 cases; the control group: 327 cases) HCC patients were finally included in this meta‐analysis. Meta‐analysis results showed that Aidi injection combined with TACE can, to some extent, enhance the clinical effect and improve the overall survival. Meanwhile, it can increase HCC patients’ quality of life. Additionally, Aidi injection plus TACE can reduce adverse events including leukopenia, gastrointestinal reaction, and liver damage in HCC patients (all P < 0.05). Therefore, Aidi injection plus TACE may significantly enhance the clinical effect, suggesting that the combination of TCM and western medicine is promising. The exact outcome needs rigorously designed performances, multicenter, and large randomized controlled trials.
Exogenous Hydrogen Sulfide Supplement Attenuates Isoproterenol‐Induced Myocardial Hypertrophy in a Sirtuin 3‐Dependent Manner
Authors: Zhang Jingyao , Yu Jin , Chen Yun , Liu Lulu , Xu Mengting , Sun Linlin , Luo Huiqin , Wang Yuqin , Meng Guoliang
Published: December 2018

Hydrogen sulfide (H2S) is a gasotransmitter with a variety of cardiovascular protective effects. Sirtuin 3 (SIRT3) is closely related to mitochondrial function and oxidative stress. We found that NaHS increased SIRT3 expression in the preventive effect on isoproterenol‐ (ISO‐) induced myocardial hypertrophy. We further investigated whether exogenous H2S supplement improved ISO‐induced myocardial hypertrophy in a SIRT3‐dependent manner. 10‐week‐old male 129S1/SvImJ (WT) mice and SIRT3 knockout (KO) mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for two weeks and then intraperitoneally injected with ISO (60 mg/kg/d) for another two weeks. In WT mice, NaHS significantly reduced the cardiac index of ISO‐induced mice, decreased the cross‐sectional area of cardiomyocytes, and inhibited the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA. The activity of total antioxidant capacity (T‐AOC) and superoxide dismutase (SOD) in the myocardium was increased, but the level of malondialdehyde (MDA) was decreased. The fluorescence intensity of dihydroethidium staining for superoxide anion was attenuated. Optic atrophy 1 (OPA1) expression was upregulated, while dynamin‐related protein 1 (DRP1) expression was downregulated. ERK, but not P38 and JNK, phosphorylation was downregulated. However, all above protective effects were unavailable in ISO‐induced SIRT3 KO mice. Our present study suggested that exogenous H2S supplement inhibited ISO‐induced cardiac hypertrophy depending on SIRT3, which might be associated with antioxidant stress.
Biochemical and Biophysical Characterization of the Enolase fromHelicobacter pylori
Authors: López-López María de J. , Rodríguez-Luna Isabel C. , Lara-Ramírez Edgar E. , López-Hidalgo Marisol , Benítez-Cardoza Claudia G. , Guo Xianwu
Published: December 2018

Enolase, which catalyses the conversion of 2-phospho-D-glycerate to phosphoenolpyruvate, is an important enzyme in the classic glycolysis pathway in cells. Enolase is highly conserved in organisms from bacteria to humans, indicating its importance in cells. Thus, enolase is a good target for developing new drugs. In the last decade, new functions of this enzyme have been found.Helicobacter pyloriis a common human pathogen that causes gastric diseases and even gastric cancer. In this study, the sequence ofH. pylorienolase (HpEno) was analysed; the conservation (at least partial) of binding sites for cofactor, plasminogen, and host extracellular RNA, as well as catalytic site, indicates that HpEno should be capable of performing the functions. Recombinant HpEno was overexpressed and purified fromE. coli. Compared to the enolases from other species, HpEno had similar characteristics for its secondary structure. The temperature-induced profiles indicate that HpEno is quite stable to temperature, compared to other homologs. Regarding the kinetics of the unfolding reaction, we found that the activation enthalpy associated with the thermal unfolding reaction is equivalent to the reported activation enthalpy for yeast enolase, indicating a similar scaffold and kinetic stability. Although a wide range of experimental conditions were assayed, it was not possible to detect any enzymatic activity of HpEno. To prove the lack of activity, still a much wider range of experiments should be carried out.
Intraoperative Treatment of Duct of Luschka during Laparoscopic Cholecystectomy: A Case Report and Revision of Literature
Authors: Masoni Luigi , Landi Leandro , Maglio Riccardo
Published: December 2018

Background. Bile leakage still remains a serious complication during cholecystectomies. In limited cases, this complication may occur from injury of the so-called ducts of Luschka. These rare ducts are usually discovered intraoperatively, and their presence poses the risk of bile injury and clinically significant bile leak. Presentation Case. We present a unique case of a 59-year-old male patient with acute cholecystitis. After removal of the gallbladder, thorough inspection of the hepatic bed was made and a little bile leak was identified from a duct of Luschka 1 cm away from the gallbladder hilum. We report on the use of endoscopic QuickClip Pro® clips (Olympus Medical Systems Corp., Tokyo, Japan) to avoid further more invasive treatment. Discussion. Endoscopic retrograde cholangiopancreatography with sphincterotomy played a crucial role for diagnosis and treatment of bile leaks with success rate near 94%. Many authors have argued the role of relaparoscopy, Diagnosis may be intraoperatively but this option does not seem to occur very often; in fact, there is a lack of data in literature. Conclusion. This is the first case report of bile leak from duct of Luschka treated during the cholecystectomies with endoscopic clip.
AKT/mTORC2 Inhibition Activates FOXO1 Function in CLL Cells Reducing B-Cell Receptor-Mediated Survival
Authors: Cosimo Emilio , Tarafdar Anuradha , Moles Michael W. , Holroyd Ailsa K. , Malik Natasha , Catherwood Mark A. , Hay Jodie , Dunn Karen M. , Macdonald Alan M. , Guichard Sylvie M. , O'Rourke Declan , Leach Michael T. , Sansom Owen J. , Cosulich Sabina C. , McCaig Alison M. , Michie Alison M.
Published: December 2018

Purpose:

To determine whether inhibition of mTOR kinase-mediated signaling represents a valid therapeutic approach for chronic lymphocytic leukemia (CLL).

Experimental Design:

Stratification of mTOR activity was carried out in patients with primary CLL samples and an aggressive CLL-like mouse model. The potency of dual mTOR inhibitor AZD8055 to induce apoptosis in primary CLL cells was assessed in the presence/absence of B-cell receptor (BCR) ligation. Furthermore, we addressed the molecular and functional impact of dual mTOR inhibition in combination with BTK inhibitor ibrutinib.

Results:

Differential regulation of basal mTORC1 activity was observed in poor prognostic CLL samples, with elevated p4EBP1T37/46 and decreased p70S6 kinase activity, suggesting that dual mTORC1/2 inhibitors may exhibit improved response in poor prognostic CLL compared with rapalogs. AZD8055 treatment of primary CLL cells significantly reduced CLL survival in vitro compared with rapamycin, preferentially targeting poor prognostic subsets and overcoming BCR-mediated survival advantages. Furthermore, AZD8055, and clinical analog AZD2014, significantly reduced CLL tumor load in mice. AKT substrate FOXO1, while overexpressed in CLL cells of poor prognostic patients in LN biopsies, peripheral CLL cells, and mouse-derived CLL-like cells, appeared to be inactive. AZD8055 treatment partially reversed FOXO1 inactivation downstream of BCR crosslinking, significantly inhibiting FOXO1T24 phosphorylation in an mTORC2-AKT–dependent manner, to promote FOXO1 nuclear localization, activity, and FOXO1-mediated gene regulation. FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib.

Conclusions:

Our studies demonstrate that dual mTOR inhibitors show promise as future CLL therapies, particularly in combination with ibrutinib.
Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database
Authors: Hwang Ki-Tae , Kim Jongjin , Jung Jiwoong , Chang Ji Hyun , Chai Young Jun , Oh So Won , Oh Sohee , Kim Young A. , Park Sung Bae , Hwang Kyu Ri
Published: December 2018

Purpose:

To determine the prognostic roles of breast cancer subtypes in females with operable invasive breast cancer.

Experimental Design: Data of 321,958 patients from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Breast cancer subtypes were classified into four categories according to the status of hormone receptor (HRc) and HER2: HRc(+)/HER2(−), HRc(+)/HER2(+), HRc(−)/HER2(+), and HRc(−)/HER2(−).

Results:

Proportions of HRc(+)/HER2(−), HRc(+)/HER2(+), HRc(−)/HER2(+), HRc(−)/HER2(−), and unknown subtype were 70.3%, 9.4%, 3.9%, 10.4%, and 6.0%, respectively. HRc(+)/HER2(−) showed the highest 5-year breast cancer–specific survival (BCSS) rate (95.5%), followed by HRc(+)/HER2(+) (94.1%), HRc(−)/HER2(+) (89.3%), and HRc(−)/HER2(−) (83.1%). HRc(+)/HER2(−) and HRc(+)/HER2(+) showed higher 5-year overall survival (OS) rates (88.4% and 88.2%, respectively) than HRc(−)/HER2(+) and HRc(−)/HER2(−) (83.9% and 76.5%, respectively). HRc(−)/HER2(−) showed the worst BCSS irrespective of race, age, or stage. Although proportions of HRc(−)/HER2(−) in the subgroup with negative event regarding BCSS and OS were 10.4% and 10.2%, respectively, they were 34.2% and 22.7%, respectively, in the subgroup with positive event. Subtype was a significant factor in both univariable and multivariable analyses regarding both BCSS and OS (all P < 0.001).

Conclusions:

Breast cancer subtype was a significant independent prognostic factor regarding both BCSS and OS in multivariable analyses. HRc(+) subtypes showed better prognosis compared with HRc(−) subtypes regarding both BCSS and OS. HRc(−)/HER2(+) showed better prognosis than HRc(−)/HER2(−) but worse prognosis than HRc(+) subtypes regarding both BCSS and OS. The triple-negative subtype showed the worst BCSS compared with the other subtypes irrespective of race, age, or stage.
Phenotypic Heterogeneity within Members of a Family Carrying the Same RBM20 Mutation R634W
Authors: Pantou Malena P. , Gourzi Polyxeni , Gkouziouta Aggeliki , Tsiapras Dimitrios , Zygouri Christianna , Constantoulakis Pantelis , Adamopoulos Stamatis , Degiannis Dimitrios
Published: December 2018

Objective: We present the genotypic and phenotypic characterization of a family displaying dilated cardiomyopathy (DCM). Methods: The proband and his relatives underwent full cardiological assessment. Genetic analysis of the proband was performed with the use of next-generation sequencing technology. Results: In this study, we present 6 members of a family carrying the RBM20 mutation NM_001134363.2:c.1900C>T. The proband was initially diagnosed with DCM at the age of 18 years and received an implantable cardioverter defibrillator (ICD) due to ventricular arrhythmias. His brother, carrier of the mutation, has been diagnosed with borderline left ventricular function. The mutation was shown to be of paternal origin, but their father remains asymptomatic with a mild DCM, while his electrocardiogram at the initial evaluation showed a right bundle branch block pattern. The mutation was also detected in the index case’s aunt who was resuscitated from sudden cardiac death. Her echocardiography revealed early stages of DCM and a bicuspid aortic valve. Her children are both carriers of the mutation. Her daughter is unaffected, but her son has an ICD implanted due to sustained ventricular tachycardia and presents early signs of DCM. Conclusion: Our findings are the first report of co-segregation of the mutation in 6 family members, supporting its pathogenic role.
Association between Freestanding Dialysis Facility Size and Medicare Quality Incentive Program Performance Scores
Authors: Ajmal Fozia , Probst Janice , Brooks John , Hardin James , Qureshi Zaina
Published: December 2018

Background: Medicare uses a quality incentive program (QIP) criteria to evaluate care in dialysis facilities and apply monetary penalties on underperforming facilities. Smaller dialysis facilities are likely to be rural and operate on lower profit margin; therefore, such facilities are likely to underperform and face Medicare penalties. The variation in QIP scores by facility size is not yet known. We investigated the association between freestanding dialysis facility size and QIP scores. Methods: Our cross-sectional analysis compared QIP scores across levels of facility size for 5,193 freestanding dialysis facilities that received QIP scores in 2015. We used Medicare facility data including Dialysis Facility Compare, Performance Scores, Facility-Level Impact, and Area Health Resource and United States Renal Data System files for the payment year 2015. We measured the facility size using the number of dialysis stations per dialysis facility. QIP scores were used to determine the quality of care. A generalized linear model was estimated at an alpha level of 0.05. Results: Facilities operating more than 10 dialysis stations scored higher than those operating fewer. Further, facilities in the South and Northeast, not offering peritoneal dialysis, affiliated with chains (except chain 3) and spending more hours per dialysis achieved higher QIP scores. Facilities reporting a higher proportion of Hispanic patients and of patients with access to pre-end-stage renal disease (ESRD) nephrologist care achieved higher QIP scores. Conversely, facilities with a higher Black patient population and higher patient travel distances scored lower. Conclusions: The current study provides important finding about the performance of the dialysis facilities with ≤10 dialysis stations. Quality improvement strategies are needed, especially for the dialysis facilities with ≤10 stations, to prevent penalties and eventual closure of such facilities due to financial insolvency. Failure to address these issues will increase further disparities in ESRD care.