bluuebunny/crossref_metadata_2025 huggingface dataset:
Microgravity-induced ocular changes are related to body weight
Authors: Buckey Jay C. , Phillips Scott D. , Anderson Allison P. , Chepko Ariane B. , Archambault-Leger Veronique , Gui Jiang , Fellows Abigail M.
Published: May 2018

On Earth, tissue weight generates compressive forces that press on body structures and act on the walls of vessels throughout the body. In microgravity, tissues no longer have weight, and tissue compressive forces are lost, suggesting that individuals who weigh more may show greater effects from microgravity exposure. One unique effect of long-duration microgravity exposure is spaceflight-associated neuroocular syndrome (SANS), which can present with globe flattening, choroidal folds, optic disk edema, and a hyperopic visual shift. To determine whether weight or other anthropometric measures are related to ocular changes in space, we analyzed data from 45 individual long-duration astronauts (mean age 47, 36 male, 9 female, mean mission duration 165 days) who had pre- and postflight measures of disk edema, choroidal folds, and manifest ocular refraction. The mean preflight weights of astronauts who developed new choroidal folds [78.6 kg with no new folds vs. 88.6 kg with new folds ( F = 6.2, P = 0.02)] and disk edema [79.1 kg with no edema vs. 95 kg with edema ( F = 9.6, P = 0.003)] were significantly greater than those who did not. Chest and waist circumferences were also significantly greater in those who developed folds or edema. The odds of developing disk edema or new choroidal folds were 55% in the highest- and 9% in the lowest-weight quartile. In this cohort, no women developed disk edema or choroidal folds, although women also weighed significantly less than men [62.9 vs. 85.2 kg ( F = 53.2, P < 0.0001)]. Preflight body weight and anthropometric factors may predict microgravity-induced ocular changes.
Local cortical activity of distant brain areas can phase-lock to the olfactory bulb’s respiratory rhythm in the freely behaving rat
Authors: Rojas-Líbano Daniel , Wimmer del Solar Jonathan , Aguilar-Rivera Marcelo , Montefusco-Siegmund Rodrigo , Maldonado Pedro E.
Published: May 2018

An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this study, we asked if there are modulations of local cortical processing that are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through electromyography and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex, and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at ~8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at ~3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70–100 Hz) amplitude could phase-lock to the animal’s OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions.

NEW & NOTEWORTHY In freely behaving rats, we found that local cortical activity within distant brain areas can phase-lock to the respiratory rhythm, more prominently during exploratory behavior than during basal respiration conditions. The findings suggest that the respiration rhythm can provide a common neural clock to integrate activity across brain areas. Our methodology also shows that the animal’s internal rhythms can be used as a reference time frame to analyze physiological activity in free behavior conditions.
Distinct mechanisms explain the control of reach speed planning: evidence from a race model framework
Authors: Venkataratamani Prasanna Venkhatesh , Murthy Aditya
Published: May 2018

Previous studies have investigated the computational architecture underlying the voluntary control of reach movements that demands a change in position or direction of movement planning. Here we used a novel task in which subjects had to either increase or decrease the movement speed according to a change in target color that occurred randomly during a trial. The applicability of different race models to such a speed redirect task was assessed. We found that the predictions of an independent race model that instantiated an abort-and-replan strategy was consistent with all aspects of performance in the fast-to-slow speed condition. The results from modeling indicated a peculiar asymmetry, in that although the fast-to-slow speed change required inhibition, none of the standard race models was able to explain how movements changed from slow to fast speeds. Interestingly, a weighted averaging model that simulated the gradual merging of two kinematic plans explained behavior in the slow-to-fast speed task. In summary, our work shows how a race model framework can provide an understanding of how the brain controls different aspects of reach movement planning and help distinguish between an abort-and-replan strategy and merging of plans.

NEW & NOTEWORTHY For the first time, a race model framework was used to understand how reach speeds are modified. We provide evidence that a fast-to-slow speed change required aborting the current plan and a complete respecification of a new plan, while none of the race models was able to explain an instructed increase of hand movement speed, which was instead accomplished by a merging of a new kinematic plan with the existing kinematic plan.
Force feedback delay affects perception of stiffness but not action, and the effect depends on the hand used but not on the handedness
Authors: Leib Raz , Rubin Inbar , Nisky Ilana
Published: May 2018

Interaction with an object often requires the estimation of its mechanical properties. We examined whether the hand that is used to interact with the object and their handedness affected people’s estimation of these properties using stiffness estimation as a test case. We recorded participants’ responses on a stiffness discrimination of a virtual elastic force field and the grip force applied on the robotic device during the interaction. In half of the trials, the robotic device delayed the participants’ force feedback. Consistent with previous studies, delayed force feedback biased the perceived stiffness of the force field. Interestingly, in both left-handed and right-handed participants, for the delayed force field, there was even less perceived stiffness when participants used their left hand than their right hand. This result supports the idea that haptic processing is affected by laterality in the brain, not by handedness. Consistent with previous studies, participants adjusted their applied grip force according to the correct size and timing of the load force regardless of the hand that was used, the handedness, or the delay. This suggests that in all of these conditions, participants were able to form an accurate internal representation of the anticipated trajectory of the load force (size and timing) and that this representation was used for accurate control of grip force independently of the perceptual bias. Thus these results provide additional evidence for the dissociation between action and perception in the processing of delayed information.

NEW & NOTEWORTHY Introducing delay to force feedback during interaction with an elastic force field biases the perceived stiffness of the force field. We show that this bias depends on the hand that was used for probing but not on handedness. At the same time, both left-handed and right-handed participants adjusted their applied grip force while using either their left or right hands in anticipation of the correct magnitude and timing despite the delay in load force.
Real‐Time and Quantitative Measurement of Crack‐Tip Stress Intensity Factors Using Digital Holographic Interferometry
Authors: Xia Haiting , Guo Rongxin , Yan Feng , Cheng Heming
Published: May 2018

Detection of the crack in an object is a critical problem for the health monitoring of a transparent object. The real‐time and quantitative measurement of the crack‐tip stress intensity factor (SIF) remains an open issue. In this paper, an approach for real‐time and quantitative measurement for the SIFs of a Mode I crack is presented based on digital holographic interferometry (DHI). A transmission digital holographic system is established to measure the phase difference of an object wave during loading. The expression to achieve the SIF from the phase difference is formulated. To enhance the accuracy of measurement, calibrated phase unwrapping based on least‐squares and iteration and median filtering is applied to retrieve the actual phase from the noisy wrapped one. The SIFs of the Mode I crack in a transparent polymethyl methacrylate (PMMA) specimen are measured by this approach. The results are compared with the theoretical ones to demonstrate the feasibility of the proposed approach.
A Weighted Multi-Local-World Network Evolving Model and Its Application in Software Network Modeling
Authors: Li Zengyang , Liu Hui , Lu Jun-An , Li Bing
Published: May 2018

The phenomenon of local worlds (also known as communities) exists in numerous real-life networks, for example, computer networks and social networks. We proposed the Weighted Multi-Local-World (WMLW) network evolving model, taking into account (1) the dense links between nodes in a local world, (2) the sparse links between nodes from different local worlds, and (3) the different importance between intra-local-world links and inter-local-world links. On topology evolving, new links between existing local worlds and new local worlds are added to the network, while new nodes and links are added to existing local worlds. On weighting mechanism, weight of links in a local world and weight of links between different local worlds are endowed different meanings. It is theoretically proven that the strength distribution of the generated network by the WMLW model yields to a power-law distribution. Simulations show the correctness of the theoretical results. Meanwhile, the degree distribution also follows a power-law distribution. Analysis and simulation results show that the proposed WMLW model can be used to model the evolution of class diagrams of software systems.
CLDA: An Effective Topic Model for Mining User Interest Preference under Big Data Background
Authors: Qiu Lirong , Yu Jia
Published: May 2018

In the present big data background, how to effectively excavate useful information is the problem that big data is facing now. The purpose of this study is to construct a more effective method of mining interest preferences of users in a particular field in the context of today’s big data. We mainly use a large number of user text data from microblog to study. LDA is an effective method of text mining, but it will not play a very good role in applying LDA directly to a large number of short texts in microblog. In today’s more effective topic modeling project, short texts need to be aggregated into long texts to avoid data sparsity. However, aggregated short texts are mixed with a lot of noise, reducing the accuracy of mining the user’s interest preferences. In this paper, we propose Combining Latent Dirichlet Allocation (CLDA), a new topic model that can learn the potential topics of microblog short texts and long texts simultaneously. The data sparsity of short texts is avoided by aggregating long texts to assist in learning short texts. Short text filtering long text is reused to improve mining accuracy, making long texts and short texts effectively combined. Experimental results in a real microblog data set show that CLDA outperforms many advanced models in mining user interest, and we also confirm that CLDA also has good performance in recommending systems.
HPV16-E6 Oncoprotein Activates TGF-βand Wnt/β-Catenin Pathways in the Epithelium-Mesenchymal Transition of Cataracts in a Transgenic Mouse Model
Authors: Rodríguez-Uribe Genaro , Serafín-Higuera Nicolas , Damian-Morales Gabriela , Cortés-Malagón Enoc Mariano , García-Hernández Vicky , Verdejo-Torres Odette , Campos-Blázquez Jessica Paulina , Trejo-Muñoz Cynthia R. , Contreras Rubén Gerardo , Ocadiz-Delgado Rodolfo , Palacios-Reyes Carmen , Lambert Paul F. , Griep Anne E. , Mancilla-Percino Teresa , Escobar-Herrera Jaime , Álvarez-Ríos Elizabeth , Ugarte-Briones Carlos , Moreno José , Gariglio Patricio , Bonilla-Delgado José
Published: May 2018

Objective. This work aimed to determine if cataractous changes associated with EMT occurring in the K14E6 mice lenses are associated with TGF-βand Wnt/β-catenin signaling activation.Materials and Methods. Cataracts of K14E6 mice were analysed histologically; and components of TGF-βand Wnt/β-catenin signaling were evaluated by Western blot, RT-qPCR, in situ RT-PCR, IHC, or IF technics. Metalloproteinases involved in EMT were also assayed using zymography. The endogenous stabilisation of Smad7 protein was also assessed using an HDAC inhibitor.Results. The K14E6 mice, which displayed binocular cataracts in 100% of the animals, exhibited loss of tissue organisation, cortical liquefaction, and an increase in the number of hyperproliferative-nucleated cells with mesenchymal-like characteristics in the lenses. Changes in lenses’ cell morphology were due to actin filaments reorganisation, activation of TGF-βand Wnt/β-catenin pathways, and the accumulation of MTA1 protein. Finally, the stabilisation of Smad7 protein diminishes cell proliferation, as well as MTA1 protein levels.Conclusion. The HPV16-E6 oncoprotein induces EMT in transgenic mice cataracts. The molecular mechanism may involve TGF-βand Wnt/β-catenin pathways, suggesting that the K14E6 transgenic mouse could be a useful model for the study or treatment of EMT-induced cataracts.
A Method of Indefinite Krylov Subspace for Eigenvalue Problem
Authors: Aliyari M. , Ghasemi Kamalvand M.
Published: May 2018

We describe an indefinite state of Arnoldi’s method for solving the eigenvalues problems. In the following, we scrutinize the indefinite state of Lanczos’ method for solving the eigenvalue problems and we show that this method for the J-Hermitian matrices works much better than Arnoldi’s method.
Visible and Near-Infrared Reflectance Spectroscopy for Investigating Soil Mineralogy: A Review
Authors: Fang Qian , Hong Hanlie , Zhao Lulu , Kukolich Stephanie , Yin Ke , Wang Chaowen
Published: May 2018

Clay minerals are the most reactive and important inorganic components in soils, but soil mineralogy classifies as a minor topic in soil sciences. Revisiting soil mineralogy has been gradually required. Clay minerals in soils are more complex and less well crystallized than those in sedimentary rocks, and thus, they display more complicated X-ray diffraction (XRD) patterns. Traditional characterization methods such as XRD are usually expensive and time-consuming, and they are therefore inappropriate for large datasets, whereas visible and near-infrared reflectance spectroscopy (VNIR) is a quick, cost-efficient, and nondestructive technique for analyzing soil mineralogic properties of large datasets. The main objectives of this review are to bring readers up to date with information and understanding of VNIR as it relates to soil mineralogy and attracts more attention from a wide variety of readers to revisit soil mineralogy. We begin our review with a description of fundamentals of VNIR. We then review common methods to process soil VNIR spectra and summary spectral features of soil minerals with particular attention to those <2 μm fractions. We further critically review applications of chemometric methods and related model building in spectroscopic soil mineral studies. We then compare spectral measurement with multivariate calibration methods, and we suggest that they both produce excellent results depending on the situation. Finally, we suggest a few avenues of future research, including the development of theoretical calibrations of VNIR more suitable for various soil samples worldwide, better elucidation of clay mineral-soil organic carbon (SOC) interactions, and building the concept of integrated soil mapping through combined information (e.g., mineral composition, soil organic matter-SOM, SOC, pH, and moisture).
Individual Travel Behavior Modeling of Public Transport Passenger Based on Graph Construction
Authors: Liang Quan , Weng Jiancheng , Zhou Wei , Santamaria Selene Baez , Ma Jianming , Rong Jian
Published: May 2018

This paper presents a novel method for mining the individual travel behavior regularity of different public transport passengers through constructing travel behavior graph based model. The individual travel behavior graph is developed to represent spatial positions, time distributions, and travel routes and further forecasts the public transport passenger’s behavior choice. The proposed travel behavior graph is composed of macronodes, arcs, and transfer probability. Each macronode corresponds to a travel association map and represents a travel behavior. A travel association map also contains its own nodes. The nodes of a travel association map are created when the processed travel chain data shows significant change. Thus, each node of three layers represents a significant change of spatial travel positions, travel time, and routes, respectively. Since a travel association map represents a travel behavior, the graph can be considered a sequence of travel behaviors. Through integrating travel association map and calculating the probabilities of the arcs, it is possible to construct a unique travel behavior graph for each passenger. The data used in this study are multimode data matched by certain rules based on the data of public transport smart card transactions and network features. The case study results show that graph based method to model the individual travel behavior of public transport passengers is effective and feasible. Travel behavior graphs support customized public transport travel characteristics analysis and demand prediction.
Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication
Authors: Casati Costanza , Colombo Valeriana Giuseppina , Perrino Marialuisa , Rossetti Ornella Marina , Querques Marialuisa , Giacomoni Alessandro , Binaggia Agnese , Colussi Giacomo
Published: May 2018

Background. Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement.Methods. A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre) on clinical grounds alone (before Dec 2010, pre-DKT era,n=170) or according to a clinical-histological protocol (after Dec 2010, DKT era,n=132) to DKT (n=48), SKT biopsy-based protocol (“high-risk”,SKThr,n=51), or SKT clinically based protocol (“low-risk”,SKTlr,n=33). Graft and patient survival were compared between the two periods and between different transplant categories.Results. Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60–69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocolSKThrshowed worst graft and overall survival in the 60–69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol.Conclusions. Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.
Predicting Tunnel Squeezing Using Multiclass Support Vector Machines
Authors: Sun Yang , Feng Xianda , Yang Lingqiang
Published: May 2018

Tunnel squeezing is one of the major geological disasters that often occur during the construction of tunnels in weak rock masses subjected to high in situ stresses. It could cause shield jamming, budget overruns, and construction delays and could even lead to tunnel instability and casualties. Therefore, accurate prediction or identification of tunnel squeezing is extremely important in the design and construction of tunnels. This study presents a modified application of a multiclass support vector machine (SVM) to predict tunnel squeezing based on four parameters, that is, diameter (D), buried depth (H), support stiffness (K), and rock tunneling quality index (Q). We compiled a database from the literature, including 117 case histories obtained from different countries such as India, Nepal, and Bhutan, to train the multiclass SVM model. The proposed model was validated using 8‐fold cross validation, and the average error percentage was approximately 11.87%. Compared with existing approaches, the proposed multiclass SVM model yields a better performance in predictive accuracy. More importantly, one could estimate the severity of potential squeezing problems based on the predicted squeezing categories/classes.
A Lightweight Surface Reconstruction Method for Online 3D Scanning Point Cloud Data Oriented toward 3D Printing
Authors: Sheng Buyun , Zhao Feiyu , Yin Xiyan , Zhang Chenglei , Wang Hui , Huang Peide
Published: May 2018

The existing surface reconstruction algorithms currently reconstruct large amounts of mesh data. Consequently, many of these algorithms cannot meet the efficiency requirements of real-time data transmission in a web environment. This paper proposes a lightweight surface reconstruction method for online 3D scanned point cloud data oriented toward 3D printing. The proposed online lightweight surface reconstruction algorithm is composed of a point cloud update algorithm (PCU), a rapid iterative closest point algorithm (RICP), and an improved Poisson surface reconstruction algorithm (IPSR). The generated lightweight point cloud data are pretreated using an updating and rapid registration method. The Poisson surface reconstruction is also accomplished by a pretreatment to recompute the point cloud normal vectors; this approach is based on a least squares method, and the postprocessing of the PDE patch generation was based on biharmonic-like fourth-order PDEs, which effectively reduces the amount of reconstructed mesh data and improves the efficiency of the algorithm. This method was verified using an online personalized customization system that was developed with WebGL and oriented toward 3D printing. The experimental results indicate that this method can generate a lightweight 3D scanning mesh rapidly and efficiently in a web environment.
Importance of the Wrist Extensor Muscle Training: Two Cases of Elbow Flexorplasty following Traumatic Brachial Plexus Injuries
Authors: Kubota Shigeki , Kubo Tadashi , Kameda Hiromi , Itoh Yoshiyasu
Published: May 2018

The modified Steindler procedure—a reconstructive surgery used to restore elbow flexion following upper brachial plexus injuries—involves shifting the origins of the muscle groups responsible for wrist flexion and forearm pronation originating from the medial epicondyle to the proximal direction to be used as flexors of the elbow. In the postoperative rehabilitation, we focused on strengthening not only the transferred muscle but also the wrist extensor muscles as antagonist muscles. After reconstruction surgery for elbow flexion via the modified Steindler procedure for traumatic brachial plexus injury, we performed long-term rehabilitation to strengthen the antagonist muscles. As a result, in two cases, excellent elbow flexion strength and gripping strength were achieved, confirming the importance of the antagonist muscles.
Colonic Mucosal Microbiota in Colorectal Cancer: A Single-Center Metagenomic Study in Saudi Arabia
Authors: Alomair Ahmed O. , Masoodi Ibrahim , Alyamani Essam J. , Allehibi Abed A. , Qutub Adel N. , Alsayari Khalid N. , Altammami Musaad A. , Alshanqeeti Ali S.
Published: May 2018

Background and Aim. Because genetic and geographic variations in intestinal microbiota are known to exist, the focus of this study was to establish an estimation of microbiota in colorectal cancer (CRC) patients in Saudi Arabia by means of metagenomic studies.Methods. From July 2010 to November 2012, colorectal cancer patients attending our hospital were enrolled for the metagenomic studies. All underwent clinical, endoscopic, and histological assessment. Mucosal microbiota samples were collected from each patient by jet-flushing colonic mucosa with distilled water at unified segments of the colon, followed by aspiration, during colonoscopy. Total purified dsDNA was extracted and quantified prior to metagenomic sequencing using an Illumina platform. Satisfactory DNA samples (n=29) were subjected to metagenomics studies, followed by comprehensive comparative phylogenetic analysis. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota.Results. Metagenomics data on 29 patients (14 females) in the age range 38–77 years were analyzed. The majority 11 (37%) of our patients were overweight (BMI = 25–30). Rectal bleeding was the presenting symptom in 18/29 (62%), while symptomatic anemia was the presenting symptom in 11/29 (37%). The location of colon cancer was rectal in 14 (48%), while cecal growth was observed in 8 (27%). Hepatic flexure growth was found in 1 (3%), descending colonic growth was found in 2 (6%), and 4 (13%) patients had transverse colon growth. The metagenomics analysis was carried out, and a total of 3.58G reads were sequenced, and about 321.91G data were used in the analysis. This study identified 11 genera specific to colorectal cancer patients when compared to genera in the control group.Bacteroides fragilisandFusobacteriumwere found to be significantly prevalent in the carcinoma group when compared to the control group.Conclusion. The current study has given an insight into the microbiota of colorectal cancer patients in Saudi Arabia and has identified various genera significantly present in these patients when compared to those of the control group.
Osteosarcopenic Visceral Obesity and Osteosarcopenic Subcutaneous Obesity, Two New Phenotypes of Sarcopenia: Prevalence, Metabolic Profile, and Risk Factors
Authors: Perna Simone , Spadaccini Daniele , Nichetti Mara , Avanzato Ilaria , Faliva Milena Anna , Rondanelli Mariangela
Published: May 2018

Background. The main criticism of the definition of “osteosarcopenic obesity” (OSO) is the lack of division between subcutaneous and visceral fat. This study describes the prevalence, metabolic profile, and risk factors of two new phenotypes of sarcopenia: osteosarcopenic visceral obesity (OSVAT) and osteosarcopenic subcutaneous obesity (OSSAT). Methods. A standardized geriatric assessment was performed by anthropometric and biochemical measures. Dual-energy X-ray absorptiometry (DXA) was used to assess body composition, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), osteoporosis, and sarcopenia. Results. A sample of 801 subjects were assessed (247 men; 554 women). The prevalence of osteosarcopenic obesity (OSO) was 6.79%; OSSAT and OSOVAT were, respectively, 2.22% and 4.56%. OSVAT (versus the others) showed a higher level of inflammation (CRP and ESR, p<0.05), bilirubin (p<0.05), and risk of fractures (FRAX index over 15%, p<0.001). Subjects with OSSAT did not show any significant risk factors associated to obesity. Conclusions. The osteosarcopenic visceral obesity phenotype (OSVAT) seems to be associated with a higher risk of fractures, inflammation, and a worse metabolic profile. These conditions in OSVAT cohort are associated with an increase of visceral adipose tissue, while patients with OSSAT seem to benefit related to the “obesity paradox.”
Research on Stiffness of Multibackbone Continuum Robot Based on Screw Theory and Euler-Bernoulli Beam
Authors: He Bin , Xu Shoulin , Wang Zhipeng
Published: May 2018

Continuum robots have become a focus for extensive research, since they can work well in complex and confined environments. The main contribution of this paper is to establish a stiffness model of a single section multibackbone continuum robot and analyze the effect of the structural parameters of continuum robot on the overall rotation and translation stiffness. First, a stiffness model which indicates the end configuration of continuum robot under external load is deduced by the screw theory and Euler-Bernoulli beam. Then, the stiffness elements are fully analyzed, therefore, obtaining the influence of the structural parameters of continuum robot on the stiffness elements. Meanwhile, a numerical analysis of stiffness elements is given. Furthermore, the minimum and maximum rotation/translation stiffness are introduced to analyze the effect of the structural parameters of continuum robot on the overall rotation and translation stiffness. Finally, the experiments are used to validate the proposed stiffness model. The experimental results show that the proposed stiffness model of continuum robot is correct and the errors are less than 7%.
A Methodology and Toolkit for Deploying Reliable Security Policies in Critical Infrastructures
Authors: Jaïdi Faouzi , Labbene Ayachi Faten , Bouhoula Adel
Published: May 2018

Substantial advances in Information and Communication Technologies (ICT) bring out novel concepts, solutions, trends, and challenges to integrate intelligent and autonomous systems in critical infrastructures. A new generation of ICT environments (such as smart cities, Internet of Things,edge-fog-social-cloudcomputing, and big data analytics) is emerging; it has different applications to critical domains (such as transportation, communication, finance, commerce, and healthcare) and different interconnections via multiple layers of public and private networks, forming a grid of critical cyberphysical infrastructures. Protecting sensitive and private data and services in critical infrastructures is, at the same time, a main objective and a great challenge for deploying secure systems. It essentially requires setting up trusted security policies. Unfortunately, security solutions should remain compliant and regularly updated to follow and track the evolution of security threats. To address this issue, we propose an advanced methodology for deploying and monitoring the compliance of trusted access control policies. Our proposal extends the traditional life cycle of access control policies with pertinent activities. It integrates formal and semiformal techniques allowing the specification, the verification, the implementation, the reverse-engineering, the validation, the risk assessment, and the optimization of access control policies. To automate and facilitate the practice of our methodology, we introduce our systemSVIRVROthat allows managing the extended life cycle of access control policies. We refer to an illustrative example to highlight the relevance of our contributions.
Myxoid Liposarcoma: Prognostic Factors and Metastatic Pattern in a Series of 148 Patients Treated at a Single Institution
Authors: Muratori Francesco , Bettini Leonardo , Frenos Filippo , Mondanelli Nicola , Greto Daniela , Livi Lorenzo , Franchi Alessandro , Roselli Giuliana , Scorianz Maurizio , Capanna Rodolfo , Campanacci Domenico
Published: May 2018

Objectives. The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern. Methods. 148 MLs were analyzed. The sites of metastases were investigated. Results. Margins (p = 0.002), grading (p = 0,0479), and metastasis (p < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation (p = 0.0243), grading (p = 0,0055), margin (p = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases. Conclusion. Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma.
A Gradient-Based Approach for Breast DCE-MRI Analysis
Authors: Losurdo L. , Basile T. M. A. , Fanizzi A. , Bellotti R. , Bottigli U. , Carbonara R. , Dentamaro R. , Diacono D. , Didonna V. , Lombardi A. , Giotta F. , Guaragnella C. , Mangia A. , Massafra R. , Tamborra P. , Tangaro S. , La Forgia D.
Published: May 2018

Breast cancer is the main cause of female malignancy worldwide. Effective early detection by imaging studies remains critical to decrease mortality rates, particularly in women at high risk for developing breast cancer. Breast Magnetic Resonance Imaging (MRI) is a common diagnostic tool in the management of breast diseases, especially for high-risk women. However, during this examination, both normal and abnormal breast tissues enhance after contrast material administration. Specifically, the normal breast tissue enhancement is known as background parenchymal enhancement: it may represent breast activity and depends on several factors, varying in degree and distribution in different patients as well as in the same patient over time. While a light degree of normal breast tissue enhancement generally causes no interpretative difficulties, a higher degree may cause difficulty to detect and classify breast lesions at Magnetic Resonance Imaging even for experienced radiologists. In this work, we intend to investigate the exploitation of some statistical measurements to automatically characterize the enhancement trend of the whole breast area in both normal and abnormal tissues independently from the presence of a background parenchymal enhancement thus to provide a diagnostic support tool for radiologists in the MRI analysis.
Accelerated Particle Swarm Optimization to Solve Large-Scale Network Plan Optimization of Resource-Leveling with a Fixed Duration
Authors: Zhang Houxian , Yang Zhaolan
Published: May 2018

Large-scale network plan optimization of resource-leveling with a fixed duration is challenging in project management. Particle swarm optimization (PSO) has provided an effective way to solve this problem in recent years. Although the previous algorithms have provided a way to accelerate the optimization of large-scale network plan by optimizing the initial particle swarm, how to more effectively accelerate the optimization of large-scale network plan with PSO is still an issue worth exploring. The main aim of this study was to develop an accelerated particle swarm optimization (APSO) for the large-scale network plan optimization of resource-leveling with a fixed duration. By adjusting the acceleration factor, the large-scale network plan optimization of resource-leveling with a fixed duration yielded a better result in this study than previously reported. Computational results demonstrated that, for the same large-scale network plan, the proposed algorithm improved the leveling criterion by 24% compared with previous solutions. APSO proposed in this study was similar in form to, but different from, particle swarm optimization with contraction factor (PSOCF). PSOCF did not have as good adaptability as APSO for network plan optimization. Accelerated convergence particle swarm optimization (ACPSO) is similar in form to the APSO proposed in this study, but its irrationality was pointed out in this study by analyzing the iterative matrix convergence.
Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression
Authors: Kumar Dhruv , New Jacob , Vishwakarma Vikalp , Joshi Radhika , Enders Jonathan , Lin Fangchen , Dasari Sumana , Gutierrez Wade R. , Leef George , Ponnurangam Sivapriya , Chavan Hemantkumar , Ganaden Lydia , Thornton Mackenzie M. , Dai Hongying , Tawfik Ossama , Straub Jeffrey , Shnayder Yelizaveta , Kakarala Kiran , Tsue Terance Ted , Girod Douglas A. , Van Houten Bennett , Anant Shrikant , Krishnamurthy Partha , Thomas Sufi Mary
Published: May 2018

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.

Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769–82. ©2018 AACR.
An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer
Authors: Lu Xin , Pan Xiaolu , Wu Chang-Jiun , Zhao Di , Feng Shan , Zang Yong , Lee Rumi , Khadka Sunada , Amin Samirkumar B. , Jin Eun-Jung , Shang Xiaoying , Deng Pingna , Luo Yanting , Morgenlander William R. , Weinrich Jacqueline , Lu Xuemin , Jiang Shan , Chang Qing , Navone Nora M. , Troncoso Patricia , DePinho Ronald A. , Wang Y. Alan
Published: May 2018

Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo. In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer.

Significance: Amplification/overexpression of PYGO2 may serve as a biomarker for prostate cancer progression and metastasis. Cancer Res; 78(14); 3823–33. ©2018 AACR.
Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients
Authors: Miloushev Vesselin Z. , Granlund Kristin L. , Boltyanskiy Rostislav , Lyashchenko Serge K. , DeAngelis Lisa M. , Mellinghoff Ingo K. , Brennan Cameron W. , Tabar Vivian , Yang T. Jonathan , Holodny Andrei I. , Sosa Ramon E. , Guo YanWei W. , Chen Albert P. , Tropp James , Robb Fraser , Keshari Kayvan R.
Published: May 2018

Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here, we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. In vivo production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, whereas production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response.

Significance: Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3755/F1.large.jpg. Cancer Res; 78(14); 3755–60. ©2018 AACR.
Tumor-Infiltrating Lymphocytes and Colorectal Cancer Survival in African American and Caucasian Patients
Authors: Wallace Kristin , Lewin David N. , Sun Shaoli , Spiceland Clayton M. , Rockey Don C. , Alekseyenko Alexander V. , Wu Jennifer D. , Baron John A. , Alberg Anthony J. , Hill Elizabeth G.
Published: May 2018

Background: Compared with Caucasian Americans (CAs), African Americans (AAs) with colorectal cancer have poorer survival, especially younger-age patients. A robust lymphocytic reaction within colorectal cancers is strongly associated with better survival, but whether immune response impacts the disparity in colorectal cancer survival is unknown.

Methods: The study population was comprised of 211 histologically confirmed colorectal cancers at the Medical University of South Carolina (Charleston, SC; 159 CAs and 52 AAs) diagnosed between Jan 01, 2000, and June 30, 2013. We constructed a lymphocyte score based on blinded pathologic assessment of the four different types of lymphocytic reactions. Cox proportional hazards regression was used to evaluate the association between the lymphocyte score and risk of death by race.

Results: Colorectal cancers in AAs (vs. CAs) had a stronger lymphocytic reaction at diagnosis. A high lymphocyte score (vs. the lowest) was associated with better survival in AAs [HR 0.19; 95% confidence interval (CI), 0.04–0.99] and CAs (HR 0.47; 95% CI, 0.15–1.45). AAs with no lymphocytic reaction (vs. other categories) had poor survival HR 4.48 (1.58–12.7) whereas no difference was observed in CAs. The risk of death in AAs (vs. CA) was more pronounced in younger patients (HR 2.92; 95% CI, 1.18–7.22) compared with older (HR 1.20; 95% CI, 0.54–2.67), especially those with lymphocytic poor colorectal cancers.

Conclusions: The lymphocytic reaction in tumor impacted the racial disparity in survival.

Impact: Our results confirm the importance of the lymphocytic score on survival and highlight the need to fully characterize the immune environment of colorectal cancers by race. Cancer Epidemiol Biomarkers Prev; 27(7); 755–61. ©2018 AACR.
Mitigating SOX2-potentiated Immune Escape of Head and Neck Squamous Cell Carcinoma with a STING-inducing Nanosatellite Vaccine
Authors: Tan Yee Sun , Sansanaphongpricha Kanokwan , Xie Yuying , Donnelly Christopher R. , Luo Xiaobo , Heath Blake R. , Zhao Xinyi , Bellile Emily , Hu Hongxiang , Chen Hongwei , Polverini Peter J. , Chen Qianming , Young Simon , Carey Thomas E. , Nör Jacques E. , Ferris Robert L. , Wolf Gregory T. , Sun Duxin , Lei Yu L.
Published: May 2018

Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape.

Experimental Design: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray, and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated antitumor immunity. To bypass SOX2-potentiated STING suppression, we engineered a novel tumor antigen–targeted nanosatellite vehicle to enhance the efficacy of STING agonist and sensitize SOX2-expressing HNSCC to checkpoint blockade.

Results: The DNA-sensing defense response is the most suppressed pathway in immune-resistant HNSCC cells. We identified SOX2 as a novel inhibitor of STING. SOX2 facilitates autophagy-dependent degradation of STING and inhibits IFN-I signaling. SOX2 potentiates an immunosuppressive microenvironment and promotes HNSCC growth in vivo in an IFN-I-dependent fashion. Our unique nanosatellite vehicle significantly enhances the efficacy of STING agonist. We show that the E6/E7–targeted nanosatellite vaccine expands the tumor-specific CD8+ T cells by over 12-fold in the tumor microenvironment and reduces tumor burden. A combination of nanosatellite vaccine with anti-PD-L1 significantly expands tumor-specific CTLs and limits the populations expressing markers for exhaustion, resulting in more effective tumor control and improved survival.

Conclusions: SOX2 dampens the immunogenicity of HNSCC by targeting the STING pathway for degradation. The nanosatellite vaccine offers a novel and effective approach to enhance the adjuvant potential of STING agonist and break cancer tolerance to immunotherapy. Clin Cancer Res; 24(17); 4242–55. ©2018 AACR.
Feasibility of Segmental Colectomy Followed by Endoscopic Surveillance as a Treatment Strategy for Colorectal Cancer Patients with Lynch Syndrome
Authors: Nagasaki Toshiya , Arai Masami , Chino Akiko , Akiyoshi Takashi , Fukunaga Yosuke , Ueno Masashi
Published: May 2018

Background: Initial surgical procedures for colorectal cancer (CRC) patients with Lynch syndrome remain controversial. This study assessed the validity of segmental colectomy (SGC) followed by endoscopic surveillance as a treatment strategy for CRC patients with Lynch syndrome. Methods: Among consecutive patients who underwent surgery for primary CRC between April 1985 and December 2014, 49 patients were observed to have germline mutations in a mismatch repair gene, and 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution were evaluated for metachronous CRC, need for secondary surgery, and the details of endoscopic surveillance. Results: Of the 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution, 6 (15.8%) patients showed metachronous CRC, 3 (7.9%) patients underwent endoscopic resection, and the other 3 patients (7.9%) underwent secondary surgery. The dispersion of the endoscopic surveillance interval was significantly greater in patients with metachronous CRC (364 ± 332.9 days) than in those without metachronous CRC (370 ± 129.7 days; p < 0.001). Conclusions: SGC followed by annual endoscopic surveillance was feasible as a treatment strategy for CRC patients with Lynch syndrome, because the incidence of metachronous CRC and the need for secondary surgery were low. Annual and periodic endoscopic surveillance might be essential for early detection of metachronous CRC and prevention of secondary surgery because of metachronous CRC in CRC patients with Lynch syndrome after SGC.