bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone marrow cavity segmentation using graph-cuts with wavelet-based texture feature
Authors: Shigeta Hironori , Mashita Tomohiro , Kikuta Junichi , Seno Shigeto , Takemura Haruo , Ishii Masaru , Matsuda Hideo
Published: August 2017

Emerging bioimaging technologies enable us to capture various dynamic cellular activities [Formula: see text]. As large amounts of data are obtained these days and it is becoming unrealistic to manually process massive number of images, automatic analysis methods are required. One of the issues for automatic image segmentation is that image-taking conditions are variable. Thus, commonly, many manual inputs are required according to each image. In this paper, we propose a bone marrow cavity (BMC) segmentation method for bone images as BMC is considered to be related to the mechanism of bone remodeling, osteoporosis, and so on. To reduce manual inputs to segment BMC, we classified the texture pattern using wavelet transformation and support vector machine. We also integrated the result of texture pattern classification into the graph-cuts-based image segmentation method because texture analysis does not consider spatial continuity. Our method is applicable to a particular frame in an image sequence in which the condition of fluorescent material is variable. In the experiment, we evaluated our method with nine types of mother wavelets and several sets of scale parameters. The proposed method with graph-cuts and texture pattern classification performs well without manual inputs by a user.
Twisted surfaces with vanishing curvature in Galilean 3-space
Authors: Dede Mustafa , Ekici Cumali , Goemans Wendy , Ünlütürk Yasin
Published: August 2017

In this work, we define twisted surfaces in Galilean 3-space. In order to construct these surfaces, a planar curve is subjected to two simultaneous rotations, possibly with different rotation speeds. The existence of Euclidean rotations and isotropic rotations leads to three distinct types of twisted surfaces in Galilean 3-space. Then we classify twisted surfaces in Galilean 3-space with zero Gaussian curvature or zero mean curvature.
Improving localization precision of Brillouin measurements using spectral autocorrelation analysis
Authors: Edrei Eitan , Nikolic Milos , Scarcelli Giuliano
Published: August 2017

Brillouin spectroscopy is a powerful tool for measuring the mechanical properties of materials without contact. The sensitivity to mechanical changes that a Brillouin spectrometer can detect is determined by the precision to which a spectral peak can be localized. The localization precision is however fundamentally limited by the low number of photons within a Brillouin measurement, as well as by intrinsic noise of the setup. Here, we present a method to improve the spectral sensitivity of Brillouin measurements by exploiting the autocorrelation function of the spectrum. We show that by performing a localization process on the autocorrelation function nearly 20% increase in localization precision can be obtained. This result is consistent between our theoretical treatment, numerical simulation and experimental results. We further study the effect of background noise on the precision improvement for realistic scenarios.
Similarity of Business Process Models—A State-of-the-Art Analysis
Authors: Schoknecht Andreas , Thaler Tom , Fettke Peter , Oberweis Andreas , Laue Ralf
Published: August 2017

Business process models play an important role in today’s enterprises, hence, model repositories may contain hundreds of models. These models are, for example, reused during process modeling activities or utilized to check the conformance of processes with legal regulations. With respect to the amount of models, such applications benefit from or even require detailed insights into the correspondences between process models or between process models’ nodes. Therefore, various process similarity and matching measures have been proposed during the past few years. This article provides an overview of the state-of-the-art regarding business process model similarity measures and aims at analyzing which similarity measures exist, how they are characterized, and what kind of calculations are typically applied to determine similarity values. Finally, the analysis of 123 similarity measures results in the suggestions to conduct further comparative analyses of similarity measures, to investigate the integration of human input into similarity measurement, and to further analyze the requirements of similarity measurement usage scenarios as future research opportunities.
Searching the Web of Things
Authors: Tran Nguyen Khoi , Sheng Quan Z. , Babar Muhammad Ali , Yao Lina
Published: August 2017

Technological advances allow more physical objects to connect to the Internet and provide their services on the Web as resources. Search engines are the key to fully utilize this emerging Web of Things, as they bridge users and applications with resources needed for their operation. Developing these systems is a challenging and diverse endeavor due to the diversity of Web of Things resources that they work with. Each combination of resources in query resolution process requires a different type of search engine with its own technical challenges and usage scenarios. This diversity complicates both the development of new systems and assessment of the state of the art. In this article, we present a systematic survey on Web of Things Search Engines (WoTSE), focusing on the diversity in forms of these systems. We collect and analyze over 200 related academic works to build a flexible conceptual model for WoTSE. We develop an analytical framework on this model to review the development of the field and its current status, reflected by 30 representative works in the area. We conclude our survey with a discussion on open issues to bridge the gap between the existing progress and an ideal WoTSE.
A Fast and Scalable Mechanism for Web Service Composition
Authors: Chattopadhyay Soumi , Banerjee Ansuman , Banerjee Nilanjan
Published: August 2017

In recent times, automated business processes and web services have become ubiquitous in diverse application spaces. Efficient composition of web services in real time while providing necessary Quality of Service (QoS) guarantees is a computationally complex problem and several heuristic based approaches have been proposed to compose the services optimally. In this article, we present the design of a scalable QoS-aware service composition mechanism that balances the computational complexity of service composition with the QoS guarantees of the composed service and achieves scalability. Our design guarantees a single QoS parameter using an intelligent search and pruning mechanism in the composed service space. We also show that our methodology yields near optimal solutions on real benchmarks. We then enhance our proposed mechanism to guarantee multiple QoS parameters using aggregation techniques. Finally, we explore search time versus solution quality tradeoff using parameterized search algorithms that produce better-quality solutions at the cost of delay. We present experimental results to show the efficiency of our proposed mechanism.
BonXai
Authors: Martens Wim , Neven Frank , Niewerth Matthias , Schwentick Thomas
Published: August 2017

While the migration from DTD to XML Schema was driven by a need for increased expressivity and flexibility, the latter was also significantly more complex to use and understand. Whereas DTDs are characterized by their simplicity, XML Schema Documents are notoriously difficult. In this article, we introduce the XML specification language BonXai, which incorporates many features of XML Schema but is arguably almost as easy to use as DTDs. In brief, the latter is achieved by sacrificing the explicit use of types in favor of simple patterns expressing contexts for elements. The goal of BonXai is not to replace XML Schema but rather to provide a simpler alternative for users who want to go beyond the expressiveness and features of DTD but do not need the explicit use of types. Furthermore, XML Schema processing tools can be used as a back-end for BonXai, since BonXai can be automatically converted into XML Schema. A particularly strong point of BonXai is its solid foundation rooted in a decade of theoretical work around pattern-based schemas. We present a formal model for a core fragment of BonXai and the translation algorithms to and from a core fragment of XML Schema. We prove that BonXai and XML Schema can be converted back-and-forth on the level of tree languages and we formally study the size trade-offs between the two languages.
Temporal Variation in Trophic Cascades
Authors: Piovia-Scott Jonah , Yang Louie H. , Wright Amber N.
Published: August 2017

The trophic cascade has emerged as a key paradigm in ecology. Although ecologists have made progress in understanding spatial variation in the strength of trophic cascades, temporal variation remains relatively unexplored. Our review suggests that strong trophic cascades are often transient, appearing when ecological conditions support high consumer abundance and rapidly growing, highly edible prey. Persistent top-down control is expected to decay over time in the absence of external drivers, as strong top-down control favors the emergence of better-defended resources. Temporal shifts in cascade strength—including those driven by contemporary global change—can either stabilize or destabilize ecological communities. We suggest that a more temporally explicit approach can improve our ability to explain the drivers of trophic cascades and predict the impact of changing cascade strength on community dynamics.
Refinement of the Affordable Care Act
Authors: Ho Vivian
Published: August 2017

Regardless of what legislation the federal government adopts to address health insurance coverage for nonelderly Americans, private insurance will likely play a major role. This article begins by listing some of the major reasons critics dislike the Affordable Care Act (ACA), then discusses the validity of these concerns from an economics perspective. Criticisms of the ACA include the increased role of government in health care, the ACA's implicit income redistribution, and concern about high and rising insurance premiums. Suggestions for refining the ACA and its market-based insurance system are then offered, with the goals of lowering insurance premiums, improving coverage rates, and/or addressing the concerns of ACA critics. Americans favor the increase in insurance coverage that has occurred under the ACA. In order to sustain this level of coverage, steps to lower Marketplace premiums through a variety of strategies affecting potential enrollees, insurers, and healthcare providers are offered.
Cancer Self-Defense: An Immune Stealth
Authors: Nakajima Kosei , Nangia-Makker Pratima , Hogan Victor , Raz Avraham
Published: August 2017

The hurdles in realizing successful cancer immunotherapy stem from the fact that cancer patients are either refractory to immune response and/or develop resistance. Here, we propose that these phenomena are due, in part, to the deployment/secretion of a “decoy flare,” for example, anomalous cancer-associated antigens by the tumor cells. The cancer secretome, which resembles the parent cell make-up, is composed of soluble macromolecules (proteins, glycans, lipids, DNAs, RNAs, etc.) and insoluble vesicles (exosomes), thus hindering cancer detection/recognition by immunotherapeutic agents, resulting in a “cancer-stealth” effect. Immunotherapy, or any treatment that relies on antigens' expression/function, could be improved by the understanding of the properties of the cancer secretome, as its clinical evaluation may change the therapeutic landscape. Cancer Res; 77(20); 5441–4. ©2017 AACR.
The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2Hi Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors
Authors: Harney Allison S. , Karagiannis George S. , Pignatelli Jeanine , Smith Bryan D. , Kadioglu Ece , Wise Scott C. , Hood Molly M. , Kaufman Michael D. , Leary Cynthia B. , Lu Wei-Ping , Al-Ani Gada , Chen Xiaoming , Entenberg David , Oktay Maja H. , Wang Yarong , Chun Lawrence , De Palma Michele , Jones Joan G. , Flynn Daniel L. , Condeelis John S.
Published: August 2017

Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation, and metastasis, which can offset the effects of chemotherapy, radiation, and antiangiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and protumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2Hi/Vegf-AHi macrophages in the tumor microenvironment of metastasis (TMEM). The antitumor effects of rebastinib enhance the efficacy of microtubule inhibiting chemotherapeutic agents, either eribulin or paclitaxel, by reducing tumor volume, metastasis, and improving overall survival. Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by protumoral Tie2+ macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis. Rebastinib is a promising therapy for achieving Tie2 inhibition in cancer patients. Mol Cancer Ther; 16(11); 2486–501. ©2017 AACR.
Animacroxam, a Novel Dual-Mode Compound Targeting Histone Deacetylases and Cytoskeletal Integrity of Testicular Germ Cell Cancer Cells
Authors: Steinemann Gustav , Dittmer Alexandra , Kuzyniak Weronika , Hoffmann Björn , Schrader Mark , Schobert Rainer , Biersack Bernhard , Nitzsche Bianca , Höpfner Michael
Published: August 2017

Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment. Animacroxam consists of an HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency. Animacroxam revealed pronounced antiproliferative, cell-cycle arresting, and apoptosis-inducing effects in TGCT cell lines with different cisplatin sensitivities. The IC50 values of animacroxam ranged from 0.22 to 0.42 μmol/L and were not correlated to the cisplatin sensitivity of the tumor cells. No unspecific cytotoxicity of animacroxam was observed in either cisplatin-sensitive or resistant TGCT cells, even at doses as high as 10 μmol/L. Furthermore, animacroxam induced the formation of actin stress fibers in cancer cells, thereby confirming the cytoskeleton-disrupting and antimigratory properties of its imidazole moiety. When compared with the clinically established HDAC inhibitor vorinostat, the novel dual-mode compound animacroxam exhibited superior antitumoral efficacy in vitro. Animacroxam also reduced the tumor size of TGCT tumors in vivo, as evidenced by performing xenograft experiments on tumor bearing chorioallantoic membranes of fertilizes chicken eggs (CAM assay). The in vivo experiments also revealed a very good tolerability of the compound, and hence, animacroxam may be a promising candidate for innovative treatment of TGCT in general and the more so for platinum-insensitive or refractory TGCT. Mol Cancer Ther; 16(11); 2364–74. ©2017 AACR.
Comparison of Different Sources of Mesenchymal Stem Cells: Palatal versus Lipoaspirated Adipose Tissue
Authors: Hakki Sema S. , Turaç Gizem , Bozkurt S. Buket , Kayis Seyit Ali , Hakki Erdogan E. , Şahin Eren , Subaşı Cansu , Karaoz Erdal
Published: August 2017

Objectives: The purpose of this study was to compare the proliferation and differentiation potential of mesenchymal stem cells (MSCs) derived from palatal adipose tissue (PAT) and lipoaspirated adipose tissue (LAT). Materials and Methods: PATs were obtained from 2 healthy female patients undergoing surgery for gingival recession, and LATs were obtained from 2 healthy female patients undergoing plastic surgery. LAT- and PAT-derived MSCs were confirmed by flow cytometry using MSC-specific surface markers. The multilineage differentiation capacity of the MSCs was analyzed. The expression of immunophenotyping, embryonic, and differentiation markers was compared between both MSC lines. The proliferation of PAT- and LAT-MSCs was evaluated using a real-time cell analyzer, and telomerase activity was determined using an ELISA-based TRAP assay. Stem cells isolated from PAT and LAT were analyzed by real-time PCR and whole genome array analysis. Results: The cells isolated from PAT had MSC characteristics. In addition, PAT-MSCs had significantly higher alkaline phosphatase activity and osteogenic potential than LAT-MSCs. Although the proliferation and telomerase activities of LAT-MSCs were higher than those of PAT-MSCs, the difference was not statistically significant. The level of embryonic stem cell markers (Oct4 and Nanog) was higher in LAT-MSCs than in PAT-MSCs. The whole genome array analysis demonstrated that 255 gene sequences were differentially expressed, with more than a twofold change in expression. Conclusions: This is the first comparative analysis of the isolation and characterization of MSCs from PAT and LAT. PAT is an accessible source of MSCs, which could be used in periodontal and craniofacial tissue engineering.
Multiple Wearable Sensors in Parkinson and Huntington Disease Individuals: A Pilot Study in Clinic and at Home
Authors: Adams Jamie L. , Dinesh Karthik , Xiong Mulin , Tarolli Christopher G. , Sharma Saloni , Sheth Nirav , Aranyosi A.J. , Zhu William , Goldenthal Steven , Biglan Kevin M. , Dorsey E. Ray , Sharma Gaurav
Published: August 2017

Background: Clinician rating scales and patient-reported outcomes are the principal means of assessing motor symptoms in Parkinson disease and Huntington disease. However, these assessments are subjective and generally limited to episodic in-person visits. Wearable sensors can objectively and continuously measure motor features and could be valuable in clinical research and care. Methods: We recruited participants with Parkinson disease, Huntington disease, and prodromal Huntington disease (individuals who carry the genetic marker but do not yet exhibit symptoms of the disease), and controls to wear 5 accelerometer-based sensors on their chest and limbs for standardized in-clinic assessments and for 2 days at home. The study’s aims were to assess the feasibility of use of wearable sensors, to determine the activity (lying, sitting, standing, walking) of participants, and to survey participants on their experience. Results: Fifty-six individuals (16 with Parkinson disease, 15 with Huntington disease, 5 with prodromal Huntington disease, and 20 controls) were enrolled in the study. Data were successfully obtained from 99.3% (278/280) of sensors dispatched. On average, individuals with Huntington disease spent over 50% of the total time lying down, substantially more than individuals with prodromal Huntington disease (33%, p = 0.003), Parkinson disease (38%, p = 0.01), and controls (34%; p < 0.001). Most (86%) participants were “willing” or “very willing” to wear the sensors again. Conclusions: Among individuals with movement disorders, the use of wearable sensors in clinic and at home was feasible and well-received. These sensors can identify statistically significant differences in activity profiles between individuals with movement disorders and those without. In addition, continuous, objective monitoring can reveal disease characteristics not observed in clinic.
The Impact of Treatment Preferences in Second-Line Chemotherapy on the Prognosis of HER2-Negative Metastatic Breast Cancer
Authors: Mukai Hirofumi , Hagiwara Yasuhiro , Imi Kentaro , Isaka Hirotsugu , Watanabe Kenichi , Matsuyama Yutaka ,   for the SELECT BC Study Group
Published: August 2017

Objective: We assessed the impact of treatment preferences in second-line chemotherapy on breast cancer prognosis using the SELECT BC study. Methods: The SELECT BC study was performed in patients with HER2-negative metastatic breast cancer treated with initial chemotherapy. From these patients, 618 were assigned to 2 groups (S-1 group, 309; taxane group, 309). The S-1 and taxane groups were each subdivided into 3 groups: crossover group, protocol-recommended group, and other group, and the analysis of overall survival (OS) was performed using Cox regression with inverse probability weighting, to adjust for postrandomization confounding. Results: In the taxane group, the OS of the crossover group (39.6 months) was better than that of the protocol-recommended group (35.7 months) and the other chemotherapy group (36.9 months) (vs. the protocol-recommended group, HR 0.72 [95% CI 0.52-0.98], p  = 0.037; vs. the other chemotherapy group, HR 0.71 [95% CI 0.43-1.18], p = 0.183). In the S-1 group, there was no statistically significant difference in OS between the 3 groups. Conclusion: The study of the combination of first-line chemotherapy and second-line chemotherapy showed that S-1 might be recommended as a second-line chemotherapy in patients in whom taxane was the primary chemotherapy.
Fall-Prone Older People's Attitudes towards the Use of Virtual Reality Technology for Fall Prevention
Authors: Dockx Kim , Alcock Lisa , Bekkers Esther , Ginis Pieter , Reelick Miriam , Pelosin Elisa , Lagravinese Giovanna , Hausdorff Jeffrey M. , Mirelman Anat , Rochester Lynn , Nieuwboer Alice
Published: August 2017

Background: Virtual reality (VR) technology is a relatively new rehabilitation tool that can deliver a combination of cognitive and motor training for fall prevention. The attitudes of older people to such training are currently unclear. Objective: This study aimed to investigate: (1) the attitudes of fall-prone older people towards fall prevention exercise with and without VR; (2) attitudinal changes after intervention with and without VR; and (3) user satisfaction following fall prevention exercise with and without VR. Methods: A total of 281 fall-prone older people were randomly assigned to an experimental group receiving treadmill training augmented by VR (TT+VR, n = 144) or a control group receiving treadmill training alone (TT, n = 137). Two questionnaires were used to measure (1) attitudes towards fall prevention exercise with and without VR (AQ); and (2) user satisfaction (USQ). AQ was evaluated at baseline and after intervention. USQ was measured after intervention only. Results: The AQ revealed that most participants had positive attitudes towards fall prevention exercise at baseline (82.2%) and after intervention (80.6%; p = 0.144). In contrast, only 53.6% were enthusiastic about fall prevention exercise with VR at baseline. These attitudes positively changed after intervention (83.1%; p < 0.001), and 99.2% indicated that they enjoyed TT+VR. Correlation analyses showed that postintervention attitudes were strongly related to user satisfaction (USQ: r = 0.503; p < 0.001). Conclusions: Older people's attitudes towards fall prevention exercise with VR were positively influenced by their experience. From the perspective of the user, VR is an attractive training mode, and thus improving service provision for older people is important.
Evaluation of Transvaginal Ultrasound plus CA-125 Measurement and Prophylactic Salpingo-Oophorectomy in Women at Different Risk Levels of Ovarian Cancer: The Modena Study Group Cohort Study
Authors: Cortesi Laura , De Matteis Elisabetta , Toss Angela , Marchi Isabella , Medici Veronica , Contu Giannina , Xholli Anjeza , Grandi Giovanni , Cagnacci Angelo , Federico Massimo
Published: August 2017

Objective: To evaluate the effectiveness of transvaginal ultrasound (TVU) and serum CA-125 measurement in women at different risk of developing ovarian cancer/fallopian tube cancer (OC/FTC) and the incidence of primary peritoneal cancer (PPC) after risk-reducing salpingo-oophorectomy (RRSO). Methods: Between 2002 and 2014, 661 women at different risk of OC/FTC/PPC due to a family history or BRCA1/2 gene mutation were offered TVU and CA-125 measurement or RRSO as prevention strategies. The detection rate of OC/FTC/PPC was evaluated, and the sensitivity and specificity for CA-125 measurement and TVU were calculated. Survival and event analysis was performed for diagnosed patients. Results: After a median follow-up of 112 months, 12 OC/FTC/PPC cases were detected (2.6/1,000 persons/year). The screening sensitivity was 70%, with 73% for BRCA carriers. Six (50%) of 12 cancers were stage I or II. Among 41 women who underwent RRSO, 2 BRCA1 carriers developed a PPC (4.9%). At 61-month follow-up, overall and event-free survival were 75 and 64%, respectively. Conclusions: The cancer detection rate in women with BRCA mutation or a strong family history supports the effectiveness of our surveillance program for early diagnosis. Screening for women at lower risk of OC/FTC is not recommended. A residual risk of PPC after RRSO remains for BRCA1 carriers.
Altered Expression Profile of Circular RNAs in the Serum of Patients with Diabetic Retinopathy Revealed by Microarray
Authors: Gu Yonghao , Ke Genjie , Wang Lin , Zhou Enliang , Zhu Kai , Wei Yingying
Published: August 2017

Purpose: Diabetic retinopathy (DR) is the leading cause of blindness among working age adults. Circular RNAs (circRNAs) are a kind of noncoding RNAs that are involved in the development of some diseases. Here, we aimed to determine the possible role of circRNAs in the pathogenesis of DR by determining the expression profile of circRNAs in the serum of DR patients. Methods: Nineteen subjects with type 2 diabetes mellitus with proliferative DR (T2DR), 15 subjects with type 2 diabetes mellitus without DR (T2DM), and 21 age-matched nondiabetic control subjects were included in the study. Expression profiles in the serum samples from 5 subjects of each group were studied by circular microarray and validated by quantitative real-time polymerase chain re- action (qRT-PCR) in another 40 subjects. Bioinformatic software was used to predict the microRNA response elements. Results: Thirty circRNAs were significantly upregulated in the serum of T2DR patients compared with the serum from both T2DM and control patients. Further, the altered expression of 7 circRNAs (hsa_circRNA_063981, hsa_circRNA_ 404457, hsa_circRNA_100750, hsa_circRNA_406918, hsa_ circRNA_104387, hsa_circRNA_103410, and hsa_circRNA_ 100192) were verified by qRT-PCR. Conclusion: This study suggested a potential role of circRNAs in the pathogenesis of DR and provides novel molecular targets for clinical therapy.
Intramedullary Thoracic Spine Astrocytoma Presenting as Hydrocephalus in an Infant: A Case Report
Authors: Rangwala Shivani D. , Oh Gerald , Barks Ashley L. , Nikas Demetrios C.
Published: August 2017

We present the case of an intramedullary spinal cord tumor from C7 to T4, classified as a WHO grade I pilocytic astrocytoma, manifesting solely with isolated, acute hydrocephalus and a normal neurological exam in a 5-month-old infant. We discuss the common presenting symptoms of spinal cord tumors in the pediatric population and possible anatomical explanations for this unique presentation and offer recommendations for the management of isolated hydrocephalus in an infant.
Associations between Type 2 Diabetes Mellitus and Arterial Stiffness: A Prospective Analysis Based on the Maine-Syracuse Study
Authors: Elias Merrill F. , Crichton Georgina E. , Dearborn Peter J. , Robbins Michael A. , Abhayaratna Walter P.
Published: August 2017

Background: The aim of this study was to investigate prospective associations between type 2 diabetes mellitus status and the gold standard non-invasive method for ascertaining arterial stiffness, carotid femoral pulse wave velocity. Methods: The prospective analysis employed 508 community-dwelling participants (mean age 61 years, 60% women) from the Maine-Syracuse Longitudinal Study. Pulse wave velocity at wave 7 (2006-2010) was compared between those with type 2 diabetes mellitus at wave 6 (2001-2006) (n = 52) and non-diabetics at wave 6 (n = 456), with adjustment for demographic factors, cardiovascular risk factors and lifestyle- and pulse wave velocity-related factors. Results: Type 2 diabetes mellitus status was associated with a significantly higher pulse wave velocity (12.5 ± 0.36 vs. 10.4 ± 0.12 m/s). Multivariate adjustment for other cardiovascular risk factors and lifestyle- and pulse wave velocity-related variables did not attenuate the findings. The risk of an elevated pulse wave velocity (≥12 m/s) was over 9 times higher for those with uncontrolled type 2 diabetes mellitus than for those without diabetes (OR 9.14, 95% CI 3.23-25.9, p < 0.001). Conclusions: Type 2 diabetes mellitus, particularly if uncontrolled, is significantly associated with risk of arterial stiffness later in life. Effective management of diabetes mellitus is an important element of protection from arterial stiffness.
Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier
Authors: Abal Paula , Louzao M. Carmen , Fraga María , Vilariño Natalia , Ferreiro Sara , Vieytes Mercedes R. , Botana Luis M.
Published: August 2017

Background: Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellates genera Azadinium and Amphidoma. These toxins cause azaspiracid poisoning (AZP), characterized by severe gastrointestinal illness in humans after the consumption of bivalve molluscs contaminated with AZAs. The main aim of the present study was to examine the consequences of human exposure to AZA1 by the study of absorption and effects of the toxin on Caco-2 cells, a reliable model of the human intestine. Methods: The ability of AZA1 to cross the human intestinal epithelium has been evaluated by the Caco-2 transepithelial permeability assay. The toxin has been detected and quantified using a microsphere-based immunoassay. Cell alterations and ultrastructural effects has been observed with confocal and transmission electron microscopy Results: AZA1 was absorbed by Caco-2 cells in a dose-dependent way without affecting cell viability. However, modifications on occludin distribution detected by confocal microscopy imaging indicated a possible monolayer integrity disruption. Nevertheless, transmission electron microscopy imaging revealed ultrastructural damages at the nucleus and mitochondria with autophagosomes in the cytoplasm, however, tight junctions and microvilli remained unaffected. Conclusion: After the ingestion of molluscs with the AZA1, the toxin will be transported through the human intestinal barrier to blood causing damage on epithelial cells.
ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway
Authors: Zhang Xin , Ding Changrui , Tian Hongfang , Dong Xinjun , Meng Xianfu , Zhu Wenwei , Liu Bing , Wang Lan , Huang Min , Li Chengxin
Published: August 2017

Background/Aims: Cutaneous melanoma is one of the leading causes of cancer deaths with an increasing incidence worldwide. A KRAB-containing zinc finger protein member, zinc finger 23 (ZNF23), was reduced in some types of tumors and inhibited cell growth by inducing cell cycle arrest. However, the role of ZNF23 expression is still poorly understood in melanoma. Methods: The level of ZNF23 expression was detected in cutaneous melanoma, adjacent normal skin tissues and cutaneous melanoma cell lines using immunohistochemistry and western blotting. The correlations between ZNF23 expression and other clinicopathologic parameters were analyzed in melanoma patients. Ectopic expression of ZNF23 plasmid was transfected into melanoma cells, SK-MEL-1 and SK-MEL-28. MTT, flow cytometry and transwell assay were used to measure cell proliferation, apoptosis, invasion and migration abilities, respectively. Mitochondrial functions and structures were detected by mitochondrial membrane potential assay and Transmission electron microscopy (TEM) method in melanoma cells transfected with overexpressing ZNF23 plasmid or empty vector. Western blotting was performed to detect the levels of ZNF23, p53, p27, Bcl-2 and cleaved caspase-3 after overexpressing of ZNF23 in melanoma cells. Results: ZNF23 was elevated in adjacent normal skin tissues compared with melanoma tissues. Patients with low level of ZNF23 expression exhibited higher incidence of lymphoid metastasis, thicker size of tumors and worse outcome. By using Cox’s regression analysis, ZNF23 expression, tumor thickness and lymph node metastasis were the independent prognostic factors for overall survival (p < 0.05). Results from cellular experiments indicated that ectopic expression of ZNF23 induced cell apoptosis by activation of caspase-3, p27, p53 expression and down-regulation of Bcl-2 through mitochondria-dependent pathway. Conclusions: Decreased ZNF23 was contributed to melanoma progression and poor survival with mitochondria-dependent pathway. It indicated that ZNF23 could be a promising therapeutic biomarker candidate for cutaneous melanoma.
CRISPR-Cas9 Genome Editing for Treatment of Atherogenic Dyslipidemia
Authors: Chadwick Alexandra C. , Musunuru Kiran
Published: August 2017

Although human genetics has resulted in the identification of novel lipid-related genes that can be targeted for the prevention of atherosclerotic vascular disease, medications targeting these genes or their protein products have short-term effects and require frequent administration during the course of the lifetime for maximal benefit. Genome-editing technologies, such as CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR–associated 9) have the potential to permanently alter genes in the body and produce long-term and even lifelong protection against atherosclerosis. In this review, we discuss recent advances in genome-editing technologies and early proof-of-concept studies of somatic in vivo genome editing in mice that highlight the potential of genome editing to target disease-related genes in patients, which would establish a novel therapeutic paradigm for atherosclerosis.
Tortuous Microvessels Contribute to Wound Healing via Sprouting Angiogenesis
Authors: Chong Diana C. , Yu Zhixian , Brighton Hailey E. , Bear James E. , Bautch Victoria L.
Published: August 2017

Objective—

Wound healing is accompanied by neoangiogenesis, and new vessels are thought to originate primarily from the microcirculation; however, how these vessels form and resolve during wound healing is poorly understood. Here, we investigated properties of the smallest capillaries during wound healing to determine their spatial organization and the kinetics of formation and resolution.

Approach and Results—

We used intravital imaging and high-resolution microscopy to identify a new type of vessel in wounds, called tortuous microvessels. Longitudinal studies showed that tortuous microvessels increased in frequency after injury, normalized as the wound healed, and were closely associated with the wound site. Tortuous microvessels had aberrant cell shapes, increased permeability, and distinct interactions with circulating microspheres, suggesting altered flow dynamics. Moreover, tortuous microvessels disproportionately contributed to wound angiogenesis by sprouting exuberantly and significantly more frequently than nearby normal capillaries.

Conclusions—

A new type of transient wound vessel, tortuous microvessels, sprout dynamically and disproportionately contribute to wound-healing neoangiogenesis, likely as a result of altered properties downstream of flow disturbances. These new findings suggest entry points for therapeutic intervention.
Regional Dysfunction After Myocardial Infarction in Rats
Authors: Espe Emil K.S. , Aronsen Jan Magnus , Eriksen Morten , Sejersted Ole M. , Zhang Lili , Sjaastad Ivar
Published: August 2017

Background—

Detailed understanding of regional function after myocardial infarction (MI) is currently incomplete. We aimed at investigating regional myocardial strain and work in post-MI rats with and without heart failure.

Methods and Results—

Six weeks after induction of MI, 62 male Wistar-Hannover rats with a range of infarct sizes, plus 14 sham-operated rats, were examined by cine and phase-contrast magnetic resonance imaging. After magnetic resonance imaging, the rats were catheterized, and left ventricular pressures were recorded. Regional strain and work were calculated from the magnetic resonance imaging and pressure data. On the basis of end-diastolic left ventricular pressure, 34 MI rats were classified as nonfailing (MI
NF
) and 28 MI rats as failing (MI
CHF
). In the region remote to the infarct, the MI
NF
rats exhibited preserved strain and increased work compared with sham, whereas MI
CHF
had reduced longitudinal strain and no increase in work in this region. In the noninfarcted region adjacent to the infarct, MI
CHF
demonstrated substantially reduced work because of high levels of negative work.

Conclusions—

We have demonstrated a distinct difference in regional work between nonfailing and failing hearts after MI and offer novel insight into the relation between regional function and presence of congestion. Work analysis provided significant added value over strain analysis alone.
Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure
Authors: Meder Benjamin , Haas Jan , Sedaghat-Hamedani Farbod , Kayvanpour Elham , Frese Karen , Lai Alan , Nietsch Rouven , Scheiner Christina , Mester Stefan , Bordalo Diana Martins , Amr Ali , Dietrich Carsten , Pils Dietmar , Siede Dominik , Hund Hauke , Bauer Andrea , Holzer Daniel Benjamin , Ruhparwar Arjang , Mueller-Hennessen Matthias , Weichenhan Dieter , Plass Christoph , Weis Tanja , Backs Johannes , Wuerstle Maximilian , Keller Andreas , Katus Hugo A. , Posch Andreas E.
Published: August 2017

Background:

Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls.

Methods:

Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls.

Results:

In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected
P
≤0.05), with 3 of them reaching epigenome-wide significance at
P
≤5×10
−8
. Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure.

Conclusions:

The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.
Global Rasikas: Audience Reception for Akram Khan’s Desh
Authors: Pillai Shanti
Published: August 2017

Spectatorship is shaped by structures of feeling that link individuals to the social both in and out of the theatre. The Indian concept of “rasika,” in which reception operates at the union of knowledge and feeling, illuminates the responses of audience members who share Khan’s experience of cultural hybridity and transnational mobility, even as Khan acknowledges spectators who do not share his cultural references.
Ritual in Prague’s Velvet Carnival
Authors: Grimes Ronald L.
Published: August 2017

Each year on 17 November, the anniversary of the Czech Republic’s Velvet Revolution of 1989, NGOs and civic groups commemorate and celebrate the revolution with the Velvet Carnival (Sametové posvícení). Procession units showcase distinctive masks, leaflets, and music. Since key organizers of the first Velvet Carnival in 2012 were students of performance, religion, and philosophy, a central question among them has been the nature and function of ritual.
“My relationship to the public is changing”: Marina Abramović: In Residence
Authors: Balkin Sarah , D’Urso Sandra
Published: August 2017

Marina Abramović: In Residence (2015) was a participatory public art project that relied on “facilitators” trained in the Abramović Method. As in other later works of Abramović’s performance practice, the artist’s presence is implied in the bodies of facilitators and participants. Situating In Residence in a longer history of institutional performance takes into account Abramović’s self-positioning as the charismatic undead.
Dancing Material History: Site-Specific Performance in Michigan
Authors: Kuppers Petra
Published: August 2017

Site-specific dance in and by Northern Michigan lakes brings Petra Kuppers experientially into a different relation to environmental materiality. Autoethnographic method merges with an attention to the materiality of art practice and the difference dance makes. It beckons: let’s merge. Dancing bodyminds in space, in change, in time. Disability, precarity, economy, indigenous and settler history. Breathe in and out with the pull of edge land, the beach, the calmness of Michigan summer lakes.
Germinal: Theatre for Beginners
Authors: Goss Lindsay
Published: August 2017

On a bare stage, the four “individuals” of Halory Goerger and Antoine Defoort’s Germinal build a world, one that is neither imaginary nor real, but strictly theatrical. In this playful meditation upon the problems and pleasures of progressing from consciousness to communication, the actors’ studied amateurishness proposes a productive confusion between actor, character, and spectator.
Studies in Southeast Asian Melastoma (Melastomataceae), 3. A new species of Melastoma from Peninsular Malaysia
Authors: NEO LOUISE , WONG K.M. , TAN HUGH T.W.
Published: August 2017

Melastoma kemamanense is here described as a new species. It is characterised by broad, scabrid leaves, twigs with closely appressed scales, flowers in compact cymes, and anisomorphic stamens. It is similar to Melastoma imbricatum but differs from it by the thickly overlapping hypanthium scales and larger mature fruits. This new species is so far only known from northeast Peninsular Malaysia.
New data on winter crane flies (Diptera: Trichoceridae) of Korea with description of a new species
Authors: PETRAŠIŪNAS ANDRIUS , PODENAS SIGITAS
Published: August 2017

Species of Trichoceridae Rondani known to occur on the Korean Peninsula are reviewed; eight of these are recorded for Korea for the first time. Trichocera (Saltrichocera) sapporensis Alexander, 1935 and T. (S.) maculipennis pictipennis Alexander, 1930 are proposed as synonyms of T. (S). maculipennis punctipennis Brunetti, 1912 which is transferred to a subspecific rank. A new species—Trichocera (Saltrichocera) latipons sp. nov. is described.
The Microphysical Roles of Lower-Tropospheric versus Midtropospheric Aerosol Particles in Mature-Stage MCS Precipitation
Authors: Marinescu Peter J. , van den Heever Susan C. , Saleeby Stephen M. , Kreidenweis Sonia M. , DeMott Paul J.
Published: August 2017

Simulations of two leading-line, trailing-stratiform mesoscale convective system (MCS) events that occurred during the Midlatitude Continental Convective Clouds Experiment (MC3E) have been used to understand the relative microphysical impacts of lower- versus midtropospheric aerosol particles (APs) on MCS precipitation. For each MCS event, four simulations were conducted in which the initial vertical location and concentrations of cloud droplet nucleating APs were varied. These simulations were used to determine the precipitation response to AP vertical location. Importantly, the total integrated number and mass of the initial aerosol profiles used in the sensitivity simulations remained constant, such that differences in the simulations could be directly attributable to changes in the vertical location of cloud droplet nucleating APs. These simulations demonstrate that lower-tropospheric APs largely influenced the precipitation response directly rearward of the leading cold pool boundary. However, farther rearward in the MCS, the relative impact of lower- versus midtropospheric APs largely depended on the MCS structure, which varied between the two events because of differences in line-normal wind shear. Midtropospheric APs were able to activate new cloud droplets in the midtropospheric levels of convective updrafts and to enhance mixed-phase precipitation through increased cloud riming, and this microphysical pathway had a more significant impact on mixed-phase precipitation in weaker line-normal wind shear conditions. This result exposes the importance of properly representing midtropospheric APs when assessing aerosol effects on clouds. This study also demonstrates the utility of assessing aerosol effects within the different regions of MCSs.
Generation of Subsurface Anticyclones at Arctic Surface Fronts due to a Surface Stress
Authors: Brannigan Liam , Johnson Helen , Lique Camille , Nycander Jonas , Nilsson Johan
Published: August 2017

Isolated anticyclones are frequently observed below the mixed layer in the Arctic Ocean. Some of these subsurface anticyclones are thought to originate at surface fronts. However, previous idealized simulations with no surface stress show that only cyclone–anticyclone dipoles can propagate away from baroclinically unstable surface fronts. Numerical simulations of fronts subject to a surface stress presented here show that a surface stress in the same direction as the geostrophic flow inhibits dipole propagation away from the front. On the other hand, a surface stress in the opposite direction to the geostrophic flow helps dipoles to propagate away from the front. Regardless of the surface stress at the point of dipole formation, these dipoles can be broken up on a time scale of days when a surface stress is applied in the right direction. The dipole breakup leads to the deeper anticyclonic component becoming an isolated subsurface eddy. The breakup of the dipole occurs because the cyclonic component of the dipole in the mixed layer is subject to an additional advection because of the Ekman flow. When the Ekman transport has a component oriented from the anticyclonic part of the dipole toward the cyclonic part then the cyclone is advected away from the anticyclone and the dipole is broken up. When the Ekman transport is in other directions relative to the dipole axis, it also leads to deviations in the trajectory of the dipole. A scaling is presented for the rate at which the surface cyclone is advected that holds across a range of mixed layer depths and surface stress magnitudes in these simulations. The results may be relevant to other regions of the ocean with similar near-surface stratification profiles.